Dendritic Cell/Myeloma Fusion Vaccine for Multiple Myeloma (BMT CTN 1401)

Sponsor

National Heart, Lung, and Blood Institute (NHLBI) (NIH)

Overall Status

Completed

CT.gov ID

NCT02728102

Collaborator

Blood and Marrow Transplant Clinical Trials Network (Other), National Cancer Institute (NCI) (NIH), National Marrow Donor Program (Other)

203

Enrollment

Locations

Arms

59.7

Actual Duration (Months)

13.5

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The study is designed as a Phase II, multicenter trial of vaccination with Dendritic cell/myeloma fusions with granulocyte macrophage colony-stimulating factor (GM-CSF) adjuvant plus lenalidomide maintenance therapy versus maintenance therapy alone or with GM-CSF following autologous transplant as part of upfront treatment of multiple myeloma (MM). It is hypothesized that the dendritic cell myeloma vaccine will result in improved response in patients with multiple myeloma after autologous Hematopoietic Cell Transplant (HCT).

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma	Procedure: Tumor Cell Collection Procedure: Autologous Stem Cell Transplant Drug: Melphalan Procedure: Leukapheresis Biological: Myeloma vaccine Drug: GM-CSF Drug: Lenalidomide	Phase 2

Detailed Description

The study is a three-arm, phase II randomized, open-labeled clinical trial that randomizes patients to vaccination with Dendritic Cell (DC)/myeloma fusions/GM-CSF plus lenalidomide maintenance therapy or lenalidomide maintenance therapy with or without GM-CSF following autologous transplant as part of upfront treatment for patients diagnosed with multiple myeloma. Patients are randomized approximately 2 months post transplant and will begin maintenance lenalidomide between day 90 and 100. The primary objective of this randomized trial is to compare the proportion of patients alive and in complete response (defined as CR or sCR) at one year post transplant between patients receiving DC/myeloma vaccine/GM-CSF with lenalidomide maintenance therapy to those receiving lenalidomide maintenance therapy with or without GM-CSF.

Study Design

Study Type:

Interventional

Actual Enrollment :

203 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Phase II Multicenter Trial of Single Autologous Hematopoietic Cell Transplant Followed by Lenalidomide Maintenance for Multiple Myeloma With or Without Vaccination With Dendritic Cell/Myeloma Fusions (BMT CTN 1401)

Actual Study Start Date :

Jul 1, 2016

Actual Primary Completion Date :

Jun 30, 2020

Actual Study Completion Date :

Jun 22, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Lenalidomide, vaccine, and GM-CSF Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will undergo leukapheresis and then will receive maintenance lenalidomide with myeloma vaccine and GM-CSF.	Procedure: Tumor Cell Collection Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell preparations will be generated. Myeloma cells will be isolated and frozen for subsequent vaccine generation for patients randomized to the vaccine arm (randomization occurs after transplant and recovery). Procedure: Autologous Stem Cell Transplant Patients will receive an autologous graft with a minimum cell dose of 2.0 x 10^6 CD34+ cells/kg patient actual body weight per autologous transplantation. Drug: Melphalan Autologous hematopoietic cell transplant will be done with high-dose melphalan of 200mg/m^2 at the schedule and timing according to institutional practices. Other Names: Alkeran Procedure: Leukapheresis Blood samples will be collected through a catheter in the neck or chest and leukapheresis will be performed using standard clinical procedures. Biological: Myeloma vaccine The target dose is 3 x 10^6 fusion cells per vaccine. A minimum of 3 x 10^6 total fusion cells will be required to proceed with vaccine administration. Patients who have <3 x 10^6 total fusion cells will not proceed with vaccination. Patients will receive the DC/MM fusion vaccine on day 1 of cycles 2, 3, and 4 of lenalidomide maintenance. Vaccine will be administered by subcutaneous injection in the upper thigh. Other Names: Dendritic cell fusion vaccine DC/MM fusion vaccine Drug: GM-CSF 100 ug GM-CSF will be given subcutaneously in the upper thigh and daily for a total of 4 days of each cycle. Other Names: Granulocyte macrophage colony-stimulating factor Leukine Drug: Lenalidomide Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy. Other Names: Revlimid™
Active Comparator: Lenalidomide and GM-CSF Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will receive maintenance lenalidomide with GM-CSF.	Procedure: Tumor Cell Collection Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell preparations will be generated. Myeloma cells will be isolated and frozen for subsequent vaccine generation for patients randomized to the vaccine arm (randomization occurs after transplant and recovery). Procedure: Autologous Stem Cell Transplant Patients will receive an autologous graft with a minimum cell dose of 2.0 x 10^6 CD34+ cells/kg patient actual body weight per autologous transplantation. Drug: Melphalan Autologous hematopoietic cell transplant will be done with high-dose melphalan of 200mg/m^2 at the schedule and timing according to institutional practices. Other Names: Alkeran Drug: GM-CSF 100 ug GM-CSF will be given subcutaneously in the upper thigh and daily for a total of 4 days of each cycle. Other Names: Granulocyte macrophage colony-stimulating factor Leukine Drug: Lenalidomide Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy. Other Names: Revlimid™
Active Comparator: Maintenance Lenalidomide Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will receive maintenance lenalidomide.	Procedure: Tumor Cell Collection Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell preparations will be generated. Myeloma cells will be isolated and frozen for subsequent vaccine generation for patients randomized to the vaccine arm (randomization occurs after transplant and recovery). Procedure: Autologous Stem Cell Transplant Patients will receive an autologous graft with a minimum cell dose of 2.0 x 10^6 CD34+ cells/kg patient actual body weight per autologous transplantation. Drug: Melphalan Autologous hematopoietic cell transplant will be done with high-dose melphalan of 200mg/m^2 at the schedule and timing according to institutional practices. Other Names: Alkeran Drug: Lenalidomide Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy. Other Names: Revlimid™

Arm

Intervention/Treatment

Experimental: Lenalidomide, vaccine, and GM-CSF

Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will undergo leukapheresis and then will receive maintenance lenalidomide with myeloma vaccine and GM-CSF.

Procedure: Tumor Cell Collection

Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell preparations will be generated. Myeloma cells will be isolated and frozen for subsequent vaccine generation for patients randomized to the vaccine arm (randomization occurs after transplant and recovery).

Procedure: Autologous Stem Cell Transplant

Patients will receive an autologous graft with a minimum cell dose of 2.0 x 10^6 CD34+ cells/kg patient actual body weight per autologous transplantation.

Drug: Melphalan

Autologous hematopoietic cell transplant will be done with high-dose melphalan of 200mg/m^2 at the schedule and timing according to institutional practices.

Other Names:

Alkeran

Procedure: Leukapheresis

Blood samples will be collected through a catheter in the neck or chest and leukapheresis will be performed using standard clinical procedures.

Biological: Myeloma vaccine

The target dose is 3 x 10^6 fusion cells per vaccine. A minimum of 3 x 10^6 total fusion cells will be required to proceed with vaccine administration. Patients who have <3 x 10^6 total fusion cells will not proceed with vaccination. Patients will receive the DC/MM fusion vaccine on day 1 of cycles 2, 3, and 4 of lenalidomide maintenance. Vaccine will be administered by subcutaneous injection in the upper thigh.

Other Names:

Dendritic cell fusion vaccine

DC/MM fusion vaccine

Drug: GM-CSF

100 ug GM-CSF will be given subcutaneously in the upper thigh and daily for a total of 4 days of each cycle.

Other Names:

Granulocyte macrophage colony-stimulating factor

Leukine

Drug: Lenalidomide

Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy.

Other Names:

Revlimid™

Active Comparator: Lenalidomide and GM-CSF

Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will receive maintenance lenalidomide with GM-CSF.

Procedure: Tumor Cell Collection

Procedure: Autologous Stem Cell Transplant

Patients will receive an autologous graft with a minimum cell dose of 2.0 x 10^6 CD34+ cells/kg patient actual body weight per autologous transplantation.

Drug: Melphalan

Autologous hematopoietic cell transplant will be done with high-dose melphalan of 200mg/m^2 at the schedule and timing according to institutional practices.

Other Names:

Alkeran

Drug: GM-CSF

100 ug GM-CSF will be given subcutaneously in the upper thigh and daily for a total of 4 days of each cycle.

Other Names:

Granulocyte macrophage colony-stimulating factor

Leukine

Drug: Lenalidomide

Other Names:

Revlimid™

Active Comparator: Maintenance Lenalidomide

Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will receive maintenance lenalidomide.

Procedure: Tumor Cell Collection

Procedure: Autologous Stem Cell Transplant

Patients will receive an autologous graft with a minimum cell dose of 2.0 x 10^6 CD34+ cells/kg patient actual body weight per autologous transplantation.

Drug: Melphalan

Autologous hematopoietic cell transplant will be done with high-dose melphalan of 200mg/m^2 at the schedule and timing according to institutional practices.

Other Names:

Alkeran

Drug: Lenalidomide

Other Names:

Revlimid™

Outcome Measures

Primary Outcome Measures

Percentage of Participants With 1-year Response Rate of CR/sCR [1 year]
The primary objective of this randomized trial is to compare the proportion of patients alive and in complete response (CR or sCR) at one year post transplant between patients receiving DC/myeloma vaccine/GM-CSF with lenalidomide maintenance therapy to those receiving lenalidomide maintenance therapy with or without GM-CSF. Complete Response (CR) is defined to require all the followings: Absence of the original monoclonal paraprotein in serum and urine by routine electrophoresis and by immunofixation; Less than 5% plasma cells in a bone marrow aspirate and also on trephine bone biopsy, if biopsy is performed; No increase in size or number of lytic bone lesions on radiological investigations; Disappearance of soft tissue plasmacytomas. Stringent Complete Response (sCR) is defined to require all the followings in addition to CR: Normal free light chain ratio (FLC); Absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence.

Secondary Outcome Measures

Participants Response to Treatment [6 months, 1 year, and 2 years post-transplant and at Cycles 3(Day 57), 6(Day 141), 9(Day 225), 12(Day 309), 15 (Day 393), 18(Day 477), 21(Day 561) and 24(Day 654) of maintenance therapy]
A participant's disease status is evaluated based on the International Uniform Response Criteria per protocol. Before disease progression (PD), all disease classifications including stringent complete response (sCR), complete response (CR), very good partial remission (VGPR), partial response (PR), stable disease (SD) are relative to participant's disease status at study entry. Disease status is 'Not Evaluable' when disease assessment is not required, or disease status is missing.
Percentage of Participants With Myeloma Progression of Vaccine and Non-vaccine Arms [2 years]
The event for this endpoint is defined as disease progression from CR/sCR or progressive disease for participants not in CR/sCR, or initiation of off protocol antimyeloma therapy. The cumulative incidence of myeloma progression will be compared between the vaccine arm and the combined non-vaccine arms using Gray's test and treating death (without documentation of disease progression) as a competing risk. Participants alive without disease progression at last observation will be censored at the date of last contact.
Percentage of Participants With Myeloma Progression in Pairwise Analysis [2 years]
This is the pairwise comparison for percentage of participants with Myeloma Progression. The event for this endpoint is defined as disease progression from CR/sCR or progressive disease for participants not in CR/sCR, or initiation of off protocol antimyeloma therapy. The cumulative incidence of myeloma progression will be compared between the vaccine arm, lenalidomide/GM-CSF arm and lenalidomide alone arm using Gray's test and treating death (without documentation of disease progression) as a competing risk. Participants alive without disease progression at last observation will be censored at the date of last contact.
Percentage of Participants With Treatment-related Mortality (TRM) [2 years]
TRM is defined as death occurring in a patient from causes other than disease relapse or progression. Disease progression is the competing event for TRM. Patients alive without disease progression at last contact are considered censored for this event. TRM from time of randomization will be compared between vaccine and no-vaccine arms combined starting at time of randomization.
Percentage of Participants With Progression-Free Survival [2 years]
Death or disease progression will be considered as events for this endpoint. The time to event will be calculated as time from randomization to disease progression, death, initiation of non-protocol anti-myeloma therapy, loss to follow-up or the end of the study, whichever comes first. The Kaplan-Meier estimator will be constructed for each treatment arm. Progression-free survival was compared between the vaccine and the combined non-vaccine arms using the log-rank test.
Percentage of Participants With Progression-Free Survival in Pairwise Analysis [2 year]
This is the pairwise comparison for percentage of participants with Progression-Free Survival. Death or disease progression will be considered as events for this endpoint. The time to event will be calculated as time from randomization to disease progression, death, initiation of non-protocol anti-myeloma therapy, loss to follow-up or the end of the study, whichever comes first. The Kaplan-Meier estimator will be constructed for each treatment arm. Progression-free survival was compared between the vaccine arm, lenalidomide/GM-CSF arm and lenalidomide alone arm.
Percentage of Participants With Overall Survival [2 years]
Death from any cause is considered as events for this endpoint. The time to event is calculated as time from randomization to death, loss to follow-up or the end of the study, whichever comes first. Patients alive at the time of last observation are considered censored. The Kaplan-Meier estimator will be constructed for each treatment arm. Overall survival are compared between the vaccine and the combined non-vaccine arms from time of randomization.
Percentage of Participants With Overall Survival in Pairwise Analysis [2 years]
This is the pairwise comparison for percentage of participants with Overall Survival. Death from any cause is considered as events for this endpoint. The time to event is calculated as time from randomization to death, loss to follow-up or the end of the study, whichever comes first. Patients alive at the time of last observation are considered censored. The Kaplan-Meier estimator will be constructed for each treatment arm. Overall survival are compared between the vaccine arm, lenalidomide/GM-CSF arm and lenalidomide alone arm from time of randomization.
Number of Grade ≥ 3 Toxicities [2 years]
Toxicities are evaluated using NCI CTCAE version 4.0 at pre-maintenance initiation and during maintenance therapy monthly for the first 4 cycles and then at cycles 6, 9, 15, 21, 24, which correspond to Day 1, 29, 57, 85, 141, 225, 393, 561, and 645 post maintenance initiation. All Grade ≥ 3 toxicities will be tabulated for treatment arms. Toxicities are categorized by organ system according to the CTCAE. Toxicities that involve multiple questions per organ system are combined in one category.
Participants With Grade ≥ 3 Toxicities [2 years]
Toxicities are evaluated using NCI CTCAE version 4.0 at pre-maintenance initiation and during maintenance therapy monthly for the first 4 cycles and then at cycles 6, 9, 15, 21, 24, which correspond to Day 1, 29, 57, 85, 141, 225, 393, 561, and 645 post maintenance initiation. The number of participants experiencing Grade ≥ 3 toxicity are displayed for the vaccine and non-vaccine arms separately. The proportion of participants experiencing Grade ≥ 3 toxicity are compared between the vaccine and non-vaccine arms combined.
Number of Grade 2 and 3 Infections [2years]
Grade 2 and 3 infections, as defined by the BMT CTN Technical MOP, occurring after randomization will be reported. The incidence of definite and probable viral, fungal and bacterial infections will be tabulated for each patient.
Percentage of Participants With Grade 2 and 3 Infections [2 years]
Grade 2 and 3 infections, as defined by the BMT CTN Technical MOP, are reported on the study. The cumulative incidence of infections post randomization, treating death as a competing risk, were compared between the vaccine and the combined non-vaccine groups using the Gray's test.
Percentage of Participants With Grade 2 and 3 Infections in Pairwise Analysis [2 years]
This is the pairwise comparison for percentage of participants with Grade 2 and 3 infections. Grade 2 and 3 infections, as defined by the BMT CTN Technical MOP, are reported on the study. The cumulative incidence of infections post randomization, treating death as a competing risk, were compared between the vaccine arm, lenalidomide/GM-CSF arm and lenalidomide alone arm using the Gray's test.
Number of Participants With Minimal Residual Disease (MRD) [Pre-randomization, Post-randomization at Cycle 9]
Minimal residual disease (MRD) is defined as the presence of malignant plasma cells detected by multicolor flow cytometry among patients who are in complete remission. Multichannel flow cytometry will be used to establish MRD based on the presence of malignant plasma cells that are CD45 (-/dim), CD38+, CD138+, CD19-, CD56+ kappa or lambda restricted. The number of patients with MRD negative (MRD-) are described using frequencies at pre-randomization and 9th cycle post-randomization and compared between the vaccine arm with the no-vaccine arms combined.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Initial Inclusion Criteria:

Patients must be considered transplant eligible by the treating physician at time of study entry.
Patients must meet the criteria for symptomatic multiple myeloma prior to initiating systemic anti-myeloma treatment.
Age >18 years and ≤ 70 years at the time of enrollment
Karnofsky Performance status of ≥ 70%
Patients must have > 20% plasma cells in the bone marrow aspirate differential <60 days prior to enrollment. The required bone marrow evaluation will need to be repeated for patients who received more than 1 cycle of anti-myeloma therapy (corticosteroid with or without other anti-myeloma agents)
Patients must have received ≤ 1 cycles of systemic anti-myeloma therapy.
Renal: Creatinine clearance of ≥ 40 mL/min, estimated or calculated.

Initial Exclusion Criteria:

Patients with a prior autologous or allogeneic HCT
Patients with purely non-secretory MM [absence of a monoclonal protein (M protein) in serum as measured by electrophoresis and immunofixation and the absence of Bence Jones protein in the urine defined by use of conventional electrophoresis and immunofixation techniques and the absence of involved serum free light chain >100 mg/L]. Patients with light chain MM detected in the serum by free light chain assay are eligible.
Patients with Plasma Cell Leukemia
Patients with disease progression prior to enrollment
Patients seropositive for the human immunodeficiency virus (HIV).
Myocardial infarction within 6 months prior to enrollment or New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at screening will be documented by the investigator as not medically relevant.
Patients with active clinically significant autoimmune disease, defined as a history of requiring systemic immunosuppressive therapy and at ongoing risk for potential disease exacerbation. Patients with a history of autoimmune thyroid disease, asthma, or limited skin manifestations are potentially eligible.
Patients receiving other investigational immunotherapy or anti-myeloma drugs within 14 days before enrollment.
Patients with prior malignancies except resected basal cell carcinoma or treated cervical carcinoma in situ. Cancer treated with curative intent < 5 years prior to enrollment will not be allowed unless approved by the Protocol Officer or one of the Protocol Chairs. Cancer treated with curative intent > 5 years prior to enrollment is allowed.
Female patients who are pregnant (positive beta-HCG) or breastfeeding.
Females of childbearing potential (FCBP) or men who have sexual contact with FCBP unwilling to use contraceptive techniques (Appendix D) during the length of lenalidomide maintenance therapy.
Patients who have received mid-intensity melphalan (>50 mg IV) as part of prior therapy.
Prior organ transplant requiring immunosuppressive therapy.
Patients who previously received lenalidomide and have experienced toxicities resulting in treatment discontinuation.
Patients who experienced thromboembolic events while on full anticoagulation during prior therapy with lenalidomide or thalidomide.
Patients unwilling to take deep vein thrombosis (DVT) prophylaxis.
Patients unable or unwilling to provide informed consent.
Patients unable or unwilling to return to the transplant center for their assigned treatments.

Randomization Inclusion Criteria:

Patient received transplant < 12 months of enrollment onto BMT CTN 1401.
No disease progression since initiation of systemic anti-myeloma therapy as determined within seven days of randomization/enrollment.
Received an autologous cell transplant with melphalan 200mg/m^{2 with a minimum cell
dose of 2x10}6 CD34+ cells/kg (actual body weight).
Mucositis and gastrointestinal symptoms resolved, off hyperalimentation and intravenous hydration.
No evidence of uncontrolled infection requiring systemic therapy. Patients who completed treatment for an infection but are continuing antibiotics, anti-viral, or anti-fungal therapy for prophylaxis are eligible to continue on protocol.
Platelet count ≥75,000/mm^3 (without transfusion in previous 7 days).
Absolute neutrophil count (ANC) ≥ 1,500/mm^3 without filgrastim administration within 7 days, or pegfilgrastim within 14 days of measurement.
Hepatic: bilirubin < 2x the upper limit of normal and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 2.5x the upper limit of normal. (Patients who have been diagnosed with Gilbert's Disease are allowed to exceed the defined bilirubin value of 2x the upper limit of normal)
Renal: Creatinine clearance of ≥ 40 mL/min, estimated or calculated. Patients with creatinine clearance ≥30 but <40 will be considered with review/approval from the protocol chairs or officer if the cause of renal insufficiency is associated with multiple myeloma.
All study participants must be registered into the mandatory Revlimid REMs program, and be willing and able to comply with the requirements.
Females of childbearing potential (FCBP) as defined in section 2.7.1.1 must have a negative serum pregnancy test with a sensitivity of at least 50 mIU/mL within 10 - 14 days prior to and again within 24 hours of prescribing lenalidomide (prescriptions must be filled within 7 days)
FCBP must either commit to abstain continuously from sexual intercourse or use TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 4 weeks before she starts taking lenalidomide, during therapy, during dose interruptions, and continuing for 4 weeks following discontinuation of lenalidomide.
FCBP must agree to ongoing pregnancy testing as required by the Revlimid REMs program.
Men must agree to use a latex condom during sexual contact with females of child bearing potential even if they have had a successful vasectomy while taking lenalidomide, during dose interruptions and for 28 days after discontinuing lenalidomide.
Patients must be willing to receive DVT prophylaxis.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California, San Francisco	San Francisco	California	United States	94143
2	Emory University	Atlanta	Georgia	United States	30322
3	University of Maryland/Greenebaum Cancer Center	Baltimore	Maryland	United States	21201
4	Beth Israel Deaconess Medical Center/Dana Farber Cancer Institute	Boston	Massachusetts	United States	02215
5	University of Minnesota	Minneapolis	Minnesota	United States	55455
6	University of Nebraska Medical Center	Omaha	Nebraska	United States	68198-7680
7	Roswell Park Cancer Institute	Buffalo	New York	United States	14263
8	Mount Sinai Medical Center	New York	New York	United States	10029
9	Memorial Sloan-Kettering Cancer Center	New York	New York	United States	10065
10	University Hospitals of Cleveland/Case Western	Cleveland	Ohio	United States	44106
11	Ohio State University/Arthur G. James Cancer Hospital	Columbus	Ohio	United States	43210
12	University of Texas/MD Anderson Cancer Center	Houston	Texas	United States	77030
13	Fred Hutchinson Cancer Research Center	Seattle	Washington	United States	98109-1024
14	University of Wisconsin Hospital & Clinics	Madison	Wisconsin	United States	53792
15	Medical College of Wisconsin	Milwaukee	Wisconsin	United States	53211

Sponsors and Collaborators

National Heart, Lung, and Blood Institute (NHLBI)
Blood and Marrow Transplant Clinical Trials Network
National Cancer Institute (NCI)
National Marrow Donor Program

Investigators

Study Director: Mary Horowitz, MD, Center for International Blood and Marrow Transplant Research

Study Documents (Full-Text)

More Information

Additional Information:

Publications

None provided.

Responsible Party:

National Heart, Lung, and Blood Institute (NHLBI)

ClinicalTrials.gov Identifier:

NCT02728102

Other Study ID Numbers:

BMT CTN 1401
U01HL069294

First Posted:

Apr 5, 2016

Last Update Posted:

Aug 3, 2022

Last Verified:

Jul 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Keywords provided by National Heart, Lung, and Blood Institute (NHLBI)

Multiple Myeloma

Lenalidomide

Maintenance Therapy

Hematologic Disorders

Additional relevant MeSH terms:

Multiple Myeloma

Neoplasms, Plasma Cell

Study Results

Participant Flow

Recruitment Details

The study opened to accrual on July 25, 2016 and closed to accrual on October 12, 2018 with 203 participants enrolled from 18 participating centers. The final study database lock was done September 9, 2021.

Pre-assignment Detail

Sixty-three participants dropped out of the study prior to randomization and 140 participants received a transplant and proceeded to randomization. The reasons for dropout include insufficient tumor cells collected (n=13), withdrew consent from study (n=12), ineligible to be randomized (n=8), disease progression prior to randomization (n=6), refused or did not make it to transplantation (n=10), physician decision (n=7), manufacturing failure (n=4), lost to follow up (n=2), and insurance (n=1).

Arm/Group Title	Lenalidomide, Vaccine, and GM-CSF	Lenalidomide and GM-CSF	Maintenance Lenalidomide
Arm/Group Description	Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will undergo leukapheresis and then will receive maintenance lenalidomide with myeloma vaccine and GM-CSF. Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell will be isolated and frozen for subsequent vaccine generation. Autologous Stem Cell Transplant: Patients will receive an autologous graft of a minimum cell dose of 2.0 x 10^6 CD34+ cells/kg patient actual body weight per transplantation with high-dose melphalan of 200mg/m^2 at the schedule and timing according to institutional practices. Leukapheresis: Blood samples will be collected through a catheter in the neck or chest and leukapheresis will be performed using standard clinical procedures. Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy. Myeloma vaccine: The target dose is 3 x 10^6 fusion cells per vaccine. A minimum of 3 x 10^6 total fusion cells will be required to proceed with vaccine administration. Patients will receive the DC/MM fusion vaccine on day 1 of cycles 2, 3, and 4 of lenalidomide maintenance. GM-CSF: 100 ug GM-CSF will be given for a total of 4 days of each cycle.	Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will receive maintenance lenalidomide with GM-CSF. Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell preparations will be generated. Myeloma cells will be isolated and frozen for subsequent vaccine generation for patients randomized to the vaccine arm (randomization occurs after transplant and recovery). Autologous Stem Cell Transplant: Patients will receive an autologous graft with a minimum cell dose of 2.0 x 10^6 CD34+ cells/kg patient actual body weight per autologous transplantation. Melphalan: Autologous hematopoietic cell transplant will be done with high-dose melphalan of 200mg/m^2 at the schedule and timing according to institutional practices. Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy. GM-CSF: 100 ug GM-CSF will be given subcutaneously in the upper thigh and daily for a total of 4 days of each cycle.	Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will receive maintenance lenalidomide. Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell preparations will be generated. Myeloma cells will be isolated and frozen for subsequent vaccine generation for patients randomized to the vaccine arm (randomization occurs after transplant and recovery). Autologous Stem Cell Transplant: Patients will receive an autologous graft with a minimum cell dose of 2.0 x 10^6 CD34+ cells/kg patient actual body weight per autologous transplantation. Melphalan: Autologous hematopoietic cell transplant will be done with high-dose melphalan of 200mg/m^2 at the schedule and timing according to institutional practices. Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy.
Period Title: Overall Study
STARTED	68	37	35
COMPLETED	61	33	30
NOT COMPLETED	7	4	5

Baseline Characteristics

Arm/Group Title	Lenalidomide, Vaccine, and GM-CSF	Lenalidomide and GM-CSF	Maintenance Lenalidomide	Total
Arm/Group Description	Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will undergo leukapheresis and then will receive maintenance lenalidomide with myeloma vaccine and GM-CSF. Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell will be isolated and frozen for subsequent vaccine generation. Autologous Stem Cell Transplant: Patients will receive an autologous graft of a minimum cell dose of 2.0 x 10^6 CD34+ cells/kg patient actual body weight per transplantation with high-dose melphalan of 200mg/m^2 at the schedule and timing according to institutional practices. Leukapheresis: Blood samples will be collected through a catheter in the neck or chest and leukapheresis will be performed using standard clinical procedures. Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy. Myeloma vaccine: The target dose is 3 x 10^6 fusion cells per vaccine. A minimum of 3 x 10^6 total fusion cells will be required to proceed with vaccine administration. Patients will receive the DC/MM fusion vaccine on day 1 of cycles 2, 3, and 4 of lenalidomide maintenance. GM-CSF: 100 ug GM-CSF will be given for a total of 4 days of each cycle.	Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will receive maintenance lenalidomide with GM-CSF. Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell preparations will be generated. Myeloma cells will be isolated and frozen for subsequent vaccine generation for patients randomized to the vaccine arm (randomization occurs after transplant and recovery). Autologous Stem Cell Transplant: Patients will receive an autologous graft with a minimum cell dose of 2.0 x 10^6 CD34+ cells/kg patient actual body weight per autologous transplantation. Melphalan: Autologous hematopoietic cell transplant will be done with high-dose melphalan of 200mg/m^2 at the schedule and timing according to institutional practices. Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy. GM-CSF: 100 ug GM-CSF will be given subcutaneously in the upper thigh and daily for a total of 4 days of each cycle.	Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will receive maintenance lenalidomide. Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell preparations will be generated. Myeloma cells will be isolated and frozen for subsequent vaccine generation for patients randomized to the vaccine arm (randomization occurs after transplant and recovery). Autologous Stem Cell Transplant: Patients will receive an autologous graft with a minimum cell dose of 2.0 x 10^6 CD34+ cells/kg patient actual body weight per autologous transplantation. Melphalan: Autologous hematopoietic cell transplant will be done with high-dose melphalan of 200mg/m^2 at the schedule and timing according to institutional practices. Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy.	Total of all reporting groups
Overall Participants	68	37	35	140
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	59.3	62.3	59.1	60.0
Sex: Female, Male (Count of Participants)
Female	27 39.7%	18 48.6%	18 51.4%	63 45%
Male	41 60.3%	19 51.4%	17 48.6%	77 55%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	4 5.9%	3 8.1%	4 11.4%	11 7.9%
Not Hispanic or Latino	61 89.7%	33 89.2%	30 85.7%	124 88.6%
Unknown or Not Reported	3 4.4%	1 2.7%	1 2.9%	5 3.6%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 1.5%	0 0%	0 0%	1 0.7%
Asian	2 2.9%	2 5.4%	0 0%	4 2.9%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	8 11.8%	2 5.4%	5 14.3%	15 10.7%
White	54 79.4%	30 81.1%	28 80%	112 80%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	3 4.4%	3 8.1%	2 5.7%	8 5.7%
Karnofsky Performance Score (KPS) (Count of Participants)
100	16 23.5%	7 18.9%	9 25.7%	32 22.9%
90	29 42.6%	10 27%	14 40%	53 37.9%
80	17 25%	15 40.5%	9 25.7%	41 29.3%
70	6 8.8%	5 13.5%	3 8.6%	14 10%
Disease Response at Randomization (Count of Participants)
Stringent Complete Response (sCR)	11 16.2%	6 16.2%	4 11.4%	21 15%
Complete Response (CR)	11 16.2%	9 24.3%	9 25.7%	29 20.7%
Very Good Partial Response (VGPR)	37 54.4%	15 40.5%	17 48.6%	69 49.3%
Partial Response (PR)	9 13.2%	7 18.9%	5 14.3%	21 15%
Stable Response	0 0%	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With 1-year Response Rate of CR/sCR
Description	The primary objective of this randomized trial is to compare the proportion of patients alive and in complete response (CR or sCR) at one year post transplant between patients receiving DC/myeloma vaccine/GM-CSF with lenalidomide maintenance therapy to those receiving lenalidomide maintenance therapy with or without GM-CSF. Complete Response (CR) is defined to require all the followings: Absence of the original monoclonal paraprotein in serum and urine by routine electrophoresis and by immunofixation; Less than 5% plasma cells in a bone marrow aspirate and also on trephine bone biopsy, if biopsy is performed; No increase in size or number of lytic bone lesions on radiological investigations; Disappearance of soft tissue plasmacytomas. Stringent Complete Response (sCR) is defined to require all the followings in addition to CR: Normal free light chain ratio (FLC); Absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description
The primary analysis population includes all the randomized participants. Protocol defines primary analysis is to compare participants receiving vaccine vs those without vaccine. So no vaccine arms with or without GM-CSF are combined. Four participants withdrew consent to all study procedures before 1-year post-transplant. Of these, 2 cases on the Lenalidomide/GM-CSF arm and 2 cases on the Lenalidomide Alone arm. These participants were not evaluable for the primary endpoint and ERC confirmed.

Analysis Population Description

The primary analysis population includes all the randomized participants. Protocol defines primary analysis is to compare participants receiving vaccine vs those without vaccine. So no vaccine arms with or without GM-CSF are combined. Four participants withdrew consent to all study procedures before 1-year post-transplant. Of these, 2 cases on the Lenalidomide/GM-CSF arm and 2 cases on the Lenalidomide Alone arm. These participants were not evaluable for the primary endpoint and ERC confirmed.

Arm/Group Title	Lenalidomide, Vaccine, and GM-CSF	Lenalidomide With or Without GM-CSF
Arm/Group Description	Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will undergo leukapheresis and then will receive maintenance lenalidomide with myeloma vaccine and GM-CSF. Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell will be isolated and frozen for subsequent vaccine generation. Autologous Stem Cell Transplant: Patients will receive an autologous graft of a minimum cell dose of 2.0 x 10^6 CD34+ cells/kg patient actual body weight per transplantation with high-dose melphalan of 200mg/m^2 at the schedule and timing according to institutional practices. Leukapheresis: Blood samples will be collected through a catheter in the neck or chest and leukapheresis will be performed using standard clinical procedures. Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy. Myeloma vaccine: The target dose is 3 x 10^6 fusion cells per vaccine. A minimum of 3 x 10^6 total fusion cells will be required to proceed with vaccine administration. Patients will receive the DC/MM fusion vaccine on day 1 of cycles 2, 3, and 4 of lenalidomide maintenance. GM-CSF: 100 ug GM-CSF will be given for a total of 4 days of each cycle.	Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will receive maintenance lenalidomide with or without GM-CSF. Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell preparations will be generated. Myeloma cells will be isolated and frozen for subsequent vaccine generation for patients randomized to the vaccine arm (randomization occurs after transplant and recovery). Autologous Stem Cell Transplant: Patients will receive an autologous graft with a minimum cell dose of 2.0 x 10^6 CD34+ cells/kg patient actual body weight per autologous transplantation. Melphalan: Autologous hematopoietic cell transplant will be done with high-dose melphalan of 200mg/m^2 at the schedule and timing according to institutional practices. Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy. GM-CSF: 100 ug GM-CSF will be given subcutaneously in the upper thigh and daily for a total of 4 days of each cycle.
Measure Participants	68	68
Number (80% Confidence Interval) [percentage of participants]	52.9 77.8%	50.0 135.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lenalidomide, Vaccine, and GM-CSF, Lenalidomide With or Without GM-CSF
	Comments	The proportion of patients alive and in CR/sCR at 1 year post transplant will be described in the vaccine and no vaccine groups with 80% confidence intervals and compared between groups using a two-sample Z test comparing binomial proportions.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.3657
	Comments	A one-sided significance level of 0.10 is used to assess whether the vaccine appears promising relative to control.
	Method	Z test
	Comments

Method of Estimation	Estimation Parameter	difference in the proportions
	Estimated Value	2.9
	Confidence Interval	(2-Sided) 80% -8.8 to 14.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Lenalidomide, Vaccine, and GM-CSF, Lenalidomide With or Without GM-CSF
	Comments	A secondary analysis stratified on disease response prior to randomization between arms will be conducted using a Cochran-Mantel-Haenszel test, and a stratified odds ratio along with 80% confidence intervals will be estimated.
	Type of Statistical Test	Equivalence
	Comments	The stratified odds ratio is estimated with 80% confidence intervals.

Statistical Test of Hypothesis	p-Value	0.7461
	Comments	P-value is provided by Breslow-Day Test for Homogeneity of the Odds Ratios.
	Method	Cochran-Mantel-Haenszel
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.19
	Confidence Interval	(2-Sided) 80% 0.70 to 2.03
	Parameter Dispersion	Type: Value:
	Estimation Comments	The Cochran-Mantel-Haenszel Odds Ratio estimate is for the Stratification. Stratum 1 is sCR/CR at Randomization. Stratum 2 is VGPR/PR/Stable Response at Randomization.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Lenalidomide, Vaccine, and GM-CSF, Lenalidomide With or Without GM-CSF
	Comments	A secondary pairwise analysis of CR/sCR rates comparing the vaccine arm to Lenalidomide/GM-CSF arm at 1 year post transplant.
	Type of Statistical Test	Superiority
	Comments	The proportion of patients alive and in CR/sCR at 1 year post transplant will be compared in the vaccine arm to Lenalidomide/GM-CSF arm with 80% confidence intervals using a two-sample Z test comparing binomial proportions.

Statistical Test of Hypothesis	p-Value	0.2429
	Comments
	Method	Z test
	Comments

Method of Estimation	Estimation Parameter	difference in the proportions
	Estimated Value	7.2
	Confidence Interval	(2-Sided) 80% -6.4 to 20.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Lenalidomide, Vaccine, and GM-CSF, Lenalidomide With or Without GM-CSF
	Comments	A secondary pairwise analysis of CR rates comparing the vaccine arm to Lenalidomide alone arm at 1 year post transplant.
	Type of Statistical Test	Superiority
	Comments	The proportion of patients alive and in CR/sCR at 1 year post transplant will be compared in the vaccine arm to Lenalidomide alone arm with 80% confidence intervals using a two-sample Z test comparing binomial proportions.

Statistical Test of Hypothesis	p-Value	0.4397
	Comments
	Method	Z test
	Comments

Method of Estimation	Estimation Parameter	difference in the proportions
	Estimated Value	-1.6
	Confidence Interval	(2-Sided) 80% -15.6 to 12.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Participants Response to Treatment
Description	A participant's disease status is evaluated based on the International Uniform Response Criteria per protocol. Before disease progression (PD), all disease classifications including stringent complete response (sCR), complete response (CR), very good partial remission (VGPR), partial response (PR), stable disease (SD) are relative to participant's disease status at study entry. Disease status is 'Not Evaluable' when disease assessment is not required, or disease status is missing.
Time Frame	6 months, 1 year, and 2 years post-transplant and at Cycles 3(Day 57), 6(Day 141), 9(Day 225), 12(Day 309), 15 (Day 393), 18(Day 477), 21(Day 561) and 24(Day 654) of maintenance therapy

Outcome Measure Data

Analysis Population Description
Analysis Population includes transplanted participants.

Arm/Group Title	Lenalidomide, Vaccine, and GM-CSF	Lenalidomide and GM-CSF	Maintenance Lenalidomide
Arm/Group Description	Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will undergo leukapheresis and then will receive maintenance lenalidomide with myeloma vaccine and GM-CSF. Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell will be isolated and frozen for subsequent vaccine generation. Autologous Stem Cell Transplant: Patients will receive an autologous graft of a minimum cell dose of 2.0 x 10^6 CD34+ cells/kg patient actual body weight per transplantation with high-dose melphalan of 200mg/m^2 at the schedule and timing according to institutional practices. Leukapheresis: Blood samples will be collected through a catheter in the neck or chest and leukapheresis will be performed using standard clinical procedures. Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy. Myeloma vaccine: The target dose is 3 x 10^6 fusion cells per vaccine. A minimum of 3 x 10^6 total fusion cells will be required to proceed with vaccine administration. Patients will receive the DC/MM fusion vaccine on day 1 of cycles 2, 3, and 4 of lenalidomide maintenance. GM-CSF: 100 ug GM-CSF will be given for a total of 4 days of each cycle.	Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will receive maintenance lenalidomide with GM-CSF. Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell preparations will be generated. Myeloma cells will be isolated and frozen for subsequent vaccine generation for patients randomized to the vaccine arm (randomization occurs after transplant and recovery). Autologous Stem Cell Transplant: Patients will receive an autologous graft with a minimum cell dose of 2.0 x 10^6 CD34+ cells/kg patient actual body weight per autologous transplantation. Melphalan: Autologous hematopoietic cell transplant will be done with high-dose melphalan of 200mg/m^2 at the schedule and timing according to institutional practices. Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy. GM-CSF: 100 ug GM-CSF will be given subcutaneously in the upper thigh and daily for a total of 4 days of each cycle.	Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will receive maintenance lenalidomide. Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell preparations will be generated. Myeloma cells will be isolated and frozen for subsequent vaccine generation for patients randomized to the vaccine arm (randomization occurs after transplant and recovery). Autologous Stem Cell Transplant: Patients will receive an autologous graft with a minimum cell dose of 2.0 x 10^6 CD34+ cells/kg patient actual body weight per autologous transplantation. Melphalan: Autologous hematopoietic cell transplant will be done with high-dose melphalan of 200mg/m^2 at the schedule and timing according to institutional practices. Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy.
Measure Participants	68	37	35
Stringent Complete Response (sCR)	12 17.6%	9 24.3%	8 22.9%
Complete Response (CR)	17 25%	8 21.6%	10 28.6%
Very Good Partial Remission (VGPR)	28 41.2%	12 32.4%	13 37.1%
Partial Response (PR)	5 7.4%	5 13.5%	2 5.7%
Stable Disease (SD)	2 2.9%	1 2.7%	0 0%
Progression (PD)	0 0%	0 0%	0 0%
Dead	0 0%	0 0%	0 0%
Not Evaluable	4 5.9%	2 5.4%	2 5.7%
Stringent Complete Response (sCR)	18 26.5%	8 21.6%	9 25.7%
Complete Response (CR)	18 26.5%	8 21.6%	9 25.7%
Very Good Partial Remission (VGPR)	22 32.4%	12 32.4%	10 28.6%
Partial Response (PR)	4 5.9%	7 18.9%	3 8.6%
Stable Disease (SD)	0 0%	0 0%	0 0%
Progression (PD)	5 7.4%	0 0%	2 5.7%
Dead	1 1.5%	0 0%	0 0%
Not Evaluable	0 0%	2 5.4%	2 5.7%
Stringent Complete Response (sCR)	17 25%	7 18.9%	9 25.7%
Complete Response (CR)	13 19.1%	6 16.2%	10 28.6%
Very Good Partial Remission (VGPR)	15 22.1%	15 40.5%	3 8.6%
Partial Response (PR)	6 8.8%	4 10.8%	2 5.7%
Stable Disease (SD)	0 0%	0 0%	0 0%
Progression (PD)	2 2.9%	0 0%	0 0%
Dead	2 2.9%	0 0%	1 2.9%
Not Evaluable	13 19.1%	5 13.5%	10 28.6%
Stringent Complete Response (sCR)	8 11.8%	9 24.3%	7 20%
Complete Response (CR)	19 27.9%	5 13.5%	14 40%
Very Good Partial Remission (VGPR)	35 51.5%	15 40.5%	11 31.4%
Partial Response (PR)	5 7.4%	6 16.2%	2 5.7%
Stable Disease (SD)	0 0%	0 0%	0 0%
Progression (PD)	0 0%	0 0%	0 0%
Dead	0 0%	0 0%	0 0%
Not Evaluable	1 1.5%	2 5.4%	1 2.9%
Stringent Complete Response (sCR)	13 19.1%	7 18.9%	7 20%
Complete Response (CR)	18 26.5%	7 18.9%	14 40%
Very Good Partial Remission (VGPR)	28 41.2%	14 37.8%	10 28.6%
Partial Response (PR)	6 8.8%	7 18.9%	2 5.7%
Stable Disease (SD)	1 1.5%	0 0%	0 0%
Progression (PD)	1 1.5%	0 0%	0 0%
Dead	0 0%	0 0%	0 0%
Not Evaluable	1 1.5%	2 5.4%	2 5.7%
Stringent Complete Response (sCR)	16 23.5%	8 21.6%	9 25.7%
Complete Response (CR)	17 25%	7 18.9%	15 42.9%
Very Good Partial Remission (VGPR)	24 35.3%	13 35.1%	7 20%
Partial Response (PR)	6 8.8%	7 18.9%	2 5.7%
Stable Disease (SD)	0 0%	0 0%	0 0%
Progression (PD)	2 2.9%	0 0%	0 0%
Dead	0 0%	0 0%	0 0%
Not Evaluable	3 4.4%	2 5.4%	2 5.7%
Stringent Complete Response (sCR)	18 26.5%	9 24.3%	9 25.7%
Complete Response (CR)	18 26.5%	6 16.2%	10 28.6%
Very Good Partial Remission (VGPR)	20 29.4%	13 35.1%	7 20%
Partial Response (PR)	5 7.4%	7 18.9%	4 11.4%
Stable Disease (SD)	0 0%	0 0%	0 0%
Progression (PD)	0 0%	0 0%	2 5.7%
Dead	0 0%	0 0%	0 0%
Not Evaluable	7 10.3%	2 5.4%	3 8.6%
Stringent Complete Response (sCR)	18 26.5%	9 24.3%	9 25.7%
Complete Response (CR)	17 25%	5 13.5%	13 37.1%
Very Good Partial Remission (VGPR)	18 26.5%	11 29.7%	6 17.1%
Partial Response (PR)	4 5.9%	7 18.9%	2 5.7%
Stable Disease (SD)	0 0%	0 0%	0 0%
Progression (PD)	3 4.4%	0 0%	1 2.9%
Dead	0 0%	0 0%	0 0%
Not Evaluable	8 11.8%	5 13.5%	4 11.4%
Stringent Complete Response (sCR)	20 29.4%	7 18.9%	7 20%
Complete Response (CR)	16 23.5%	7 18.9%	13 37.1%
Very Good Partial Remission (VGPR)	17 25%	14 37.8%	6 17.1%
Partial Response (PR)	3 4.4%	6 16.2%	1 2.9%
Stable Disease (SD)	2 2.9%	0 0%	0 0%
Progression (PD)	1 1.5%	0 0%	1 2.9%
Dead	0 0%	0 0%	0 0%
Not Evaluable	9 13.2%	3 8.1%	7 20%
Stringent Complete Response (sCR)	20 29.4%	6 16.2%	10 28.6%
Complete Response (CR)	15 22.1%	5 13.5%	11 31.4%
Very Good Partial Remission (VGPR)	14 20.6%	17 45.9%	6 17.1%
Partial Response (PR)	5 7.4%	4 10.8%	1 2.9%
Stable Disease (SD)	0 0%	0 0%	0 0%
Progression (PD)	2 2.9%	0 0%	0 0%
Dead	1 1.5%	0 0%	0 0%
Not Evaluable	11 16.2%	5 13.5%	7 20%
Stringent Complete Response (sCR)	19 27.9%	6 16.2%	9 25.7%
Complete Response (CR)	15 22.1%	7 18.9%	11 31.4%
Very Good Partial Remission (VGPR)	14 20.6%	16 43.2%	6 17.1%
Partial Response (PR)	6 8.8%	3 8.1%	1 2.9%
Stable Disease (SD)	0 0%	0 0%	0 0%
Progression (PD)	1 1.5%	1 2.7%	0 0%
Dead	1 1.5%	0 0%	1 2.9%
Not Evaluable	12 17.6%	4 10.8%	7 20%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lenalidomide, Vaccine, and GM-CSF, Lenalidomide With or Without GM-CSF, Maintenance Lenalidomide
	Comments	The proportion of participants alive and with sCR/CR/VGPR will be compared between the vaccine and the combined non-vaccine arms at 6 months Post Transplant.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.9376
	Comments	Statistical significance was determined using a pre-specified threshold of 0.05
	Method	Chi-squared
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Lenalidomide, Vaccine, and GM-CSF, Lenalidomide With or Without GM-CSF
	Comments	In this pairwise analysis, the proportion of participants alive and with sCR/CR/VGPR will be compared between the vaccine arm and lenalidomide/GM-CSF arm at 6 months Post Transplant.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.4887
	Comments	Statistical significance was determined using a pre-specified threshold of 0.05
	Method	Chi-squared
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Lenalidomide, Vaccine, and GM-CSF, Maintenance Lenalidomide
	Comments	In this pairwise analysis, the proportion of participants alive and with sCR/CR/VGPR will be compared between the vaccine arm and lenalidomide alone arm at 6 months Post Transplant.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.5176
	Comments	Statistical significance was determined using a pre-specified threshold of 0.05
	Method	Chi-squared
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Lenalidomide With or Without GM-CSF, Maintenance Lenalidomide
	Comments	In this pairwise analysis, the proportion of participants alive and with sCR/CR/VGPR will be compared between lenalidomide/GM-CSF arm and lenalidomide alone arm at 6 months Post Transplant.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.2461
	Comments	Statistical significance was determined using a pre-specified threshold of 0.05.
	Method	Chi-squared
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Lenalidomide, Vaccine, and GM-CSF, Lenalidomide With or Without GM-CSF, Maintenance Lenalidomide
	Comments	The proportion of participants alive and with sCR/CR/VGPR will be compared between the vaccine and the combined non-vaccine arms at 1 year Post Transplant.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.2530
	Comments	Statistical significance was determined using a pre-specified threshold of 0.05
	Method	Chi-squared
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Lenalidomide, Vaccine, and GM-CSF, Lenalidomide With or Without GM-CSF
	Comments	In this pairwise analysis, the proportion of participants alive and with sCR/CR/VGPR will be compared between the vaccine arm and lenalidomide/GM-CSF arm at 1 year Post Transplant.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.2213
	Comments	Statistical significance was determined using a pre-specified threshold of 0.05.
	Method	Chi-squared
	Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Lenalidomide, Vaccine, and GM-CSF, Maintenance Lenalidomide
	Comments	In this pairwise analysis, the proportion of participants alive and with sCR/CR/VGPR will be compared between the vaccine arm and lenalidomide alone arm at 1 year Post Transplant.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.4930
	Comments	Statistical significance was determined using a pre-specified threshold of 0.05.
	Method	Chi-squared
	Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Lenalidomide With or Without GM-CSF, Maintenance Lenalidomide
	Comments	In this pairwise analysis, the proportion of participants alive and with sCR/CR/VGPR will be compared between the lenalidomide/GM-CSF arm and lenalidomide alone arm at 1 year Post Transplant.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.6591
	Comments	Statistical significance was determined using a pre-specified threshold of 0.05.
	Method	Chi-squared
	Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Lenalidomide, Vaccine, and GM-CSF, Lenalidomide With or Without GM-CSF, Maintenance Lenalidomide
	Comments	The proportion of participants alive and with sCR/CR/VGPR will be compared between the vaccine and the combined non-vaccine arms at 2 years Post Transplant.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.6790
	Comments	Statistical significance was determined using a pre-specified threshold of 0.05
	Method	Chi-squared
	Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Lenalidomide, Vaccine, and GM-CSF, Lenalidomide With or Without GM-CSF
	Comments	In this pairwise analysis, the proportion of participants alive and with sCR/CR/VGPR will be compared between the vaccine arm and lenalidomide/GM-CSF arm at 2 years Post Transplant.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.3124
	Comments	Statistical significance was determined using a pre-specified threshold of 0.05.
	Method	Chi-squared
	Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Lenalidomide, Vaccine, and GM-CSF, Maintenance Lenalidomide
	Comments	In this pairwise analysis, the proportion of participants alive and with sCR/CR/VGPR will be compared between the vaccine arm and lenalidomide alone arm at 2 years Post Transplant.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.7379
	Comments	Statistical significance was determined using a pre-specified threshold of 0.05.
	Method	Chi-squared
	Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Lenalidomide With or Without GM-CSF, Maintenance Lenalidomide
	Comments	In this pairwise analysis, the proportion of participants alive and with sCR/CR/VGPR will be compared between the lenalidomide/GM-CSF arm and lenalidomide alone arm at 2 years Post Transplant.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.2379
	Comments	Statistical significance was determined using a pre-specified threshold of 0.05.
	Method	Chi-squared
	Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Lenalidomide, Vaccine, and GM-CSF, Lenalidomide With or Without GM-CSF, Maintenance Lenalidomide
	Comments	Proportion of participants achieving CR among the subset of participants who are not in CR at the time of randomization between the vaccine and the combined non-vaccine arms at 6 months Post Transplant.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.5353
	Comments	Statistical significance was determined using a pre-specified threshold of 0.05
	Method	Chi-squared
	Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Lenalidomide, Vaccine, and GM-CSF, Lenalidomide With or Without GM-CSF, Maintenance Lenalidomide
	Comments	Proportion of participants achieving CR among the subset of participants who are not in CR at the time of randomization between the vaccine and the combined non-vaccine arms at 12 months Post Transplant.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.4417
	Comments	Statistical significance was determined using a pre-specified threshold of 0.05
	Method	Chi-squared
	Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Lenalidomide, Vaccine, and GM-CSF, Lenalidomide With or Without GM-CSF, Maintenance Lenalidomide
	Comments	Proportion of participants achieving CR among the subset of participants who are not in CR at the time of randomization between the vaccine and the combined non-vaccine arms at 24 months Post Transplant.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.9450
	Comments	Statistical significance was determined using a pre-specified threshold of 0.05
	Method	Chi-squared
	Comments

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Lenalidomide, Vaccine, and GM-CSF, Lenalidomide With or Without GM-CSF
	Comments	A pairwise analysis of proportion of participants achieving CR among the subset of participants who are not in CR at the time of randomization between the vaccine arm and lenalidomide/GM-CSF arm is conducted at 1 year post transplant.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.1599
	Comments	Statistical significance was determined using a pre-specified threshold of 0.05
	Method	Chi-squared
	Comments

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Lenalidomide, Vaccine, and GM-CSF, Maintenance Lenalidomide
	Comments	A pairwise analysis of proportion of participants achieving CR among the subset of participants who are not in CR at the time of randomization between the vaccine arm and lenalidomide alone arm is conducted at 1 year post transplant.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.8984
	Comments	Statistical significance was determined using a pre-specified threshold of 0.05
	Method	Chi-squared
	Comments

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Lenalidomide With or Without GM-CSF, Maintenance Lenalidomide
	Comments	A pairwise analysis of proportion of participants achieving CR among the subset of participants who are not in CR at the time of randomization between lenalidomide/GM-CSF arm and lenalidomide alone arm is conducted at 1 year post transplant.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.1757
	Comments	Statistical significance was determined using a pre-specified threshold of 0.05
	Method	Chi-squared
	Comments

3. Secondary Outcome

Title	Percentage of Participants With Myeloma Progression of Vaccine and Non-vaccine Arms
Description	The event for this endpoint is defined as disease progression from CR/sCR or progressive disease for participants not in CR/sCR, or initiation of off protocol antimyeloma therapy. The cumulative incidence of myeloma progression will be compared between the vaccine arm and the combined non-vaccine arms using Gray's test and treating death (without documentation of disease progression) as a competing risk. Participants alive without disease progression at last observation will be censored at the date of last contact.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description
The randomized participants are included in the analysis.

Arm/Group Title	Lenalidomide, Vaccine, and GM-CSF	Lenalidomide With or Without GM-CSF
Arm/Group Description	Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will undergo leukapheresis and then will receive maintenance lenalidomide with myeloma vaccine and GM-CSF. Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell will be isolated and frozen for subsequent vaccine generation. Autologous Stem Cell Transplant: Patients will receive an autologous graft of a minimum cell dose of 2.0 x 10^6 CD34+ cells/kg patient actual body weight per transplantation with high-dose melphalan of 200mg/m^2 at the schedule and timing according to institutional practices. Leukapheresis: Blood samples will be collected through a catheter in the neck or chest and leukapheresis will be performed using standard clinical procedures. Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy. Myeloma vaccine: The target dose is 3 x 10^6 fusion cells per vaccine. A minimum of 3 x 10^6 total fusion cells will be required to proceed with vaccine administration. Patients will receive the DC/MM fusion vaccine on day 1 of cycles 2, 3, and 4 of lenalidomide maintenance. GM-CSF: 100 ug GM-CSF will be given for a total of 4 days of each cycle.	Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will receive maintenance lenalidomide with or without GM-CSF. Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell preparations will be generated. Myeloma cells will be isolated and frozen for subsequent vaccine generation for patients randomized to the vaccine arm (randomization occurs after transplant and recovery). Autologous Stem Cell Transplant: Patients will receive an autologous graft with a minimum cell dose of 2.0 x 10^6 CD34+ cells/kg patient actual body weight per autologous transplantation. Melphalan: Autologous hematopoietic cell transplant will be done with high-dose melphalan of 200mg/m^2 at the schedule and timing according to institutional practices. Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy. GM-CSF: 100 ug GM-CSF will be given subcutaneously in the upper thigh and daily for a total of 4 days of each cycle.
Measure Participants	68	72
Number (95% Confidence Interval) [percentage of participants]	20.7 30.4%	11.8 31.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lenalidomide, Vaccine, and GM-CSF, Lenalidomide With or Without GM-CSF
	Comments	The null hypothesis is that there is no difference of Myeloma Progression between vaccine vs. non- vaccine arms.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.161
	Comments	Statistical significance was determined using a pre-specified threshold of 0.05
	Method	Gray's test for cumulative Incidence
	Comments

4. Secondary Outcome

Title	Percentage of Participants With Myeloma Progression in Pairwise Analysis
Description	This is the pairwise comparison for percentage of participants with Myeloma Progression. The event for this endpoint is defined as disease progression from CR/sCR or progressive disease for participants not in CR/sCR, or initiation of off protocol antimyeloma therapy. The cumulative incidence of myeloma progression will be compared between the vaccine arm, lenalidomide/GM-CSF arm and lenalidomide alone arm using Gray's test and treating death (without documentation of disease progression) as a competing risk. Participants alive without disease progression at last observation will be censored at the date of last contact.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description
The randomized participants are included in the analysis.

Arm/Group Title	Lenalidomide, Vaccine, and GM-CSF	Lenalidomide and GM-CSF	Maintenance Lenalidomide
Arm/Group Description	Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will undergo leukapheresis and then will receive maintenance lenalidomide with myeloma vaccine and GM-CSF. Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell will be isolated and frozen for subsequent vaccine generation. Autologous Stem Cell Transplant: Patients will receive an autologous graft of a minimum cell dose of 2.0 x 10^6 CD34+ cells/kg patient actual body weight per transplantation with high-dose melphalan of 200mg/m^2 at the schedule and timing according to institutional practices. Leukapheresis: Blood samples will be collected through a catheter in the neck or chest and leukapheresis will be performed using standard clinical procedures. Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy. Myeloma vaccine: The target dose is 3 x 10^6 fusion cells per vaccine. A minimum of 3 x 10^6 total fusion cells will be required to proceed with vaccine administration. Patients will receive the DC/MM fusion vaccine on day 1 of cycles 2, 3, and 4 of lenalidomide maintenance. GM-CSF: 100 ug GM-CSF will be given for a total of 4 days of each cycle.	Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will receive maintenance lenalidomide with GM-CSF. Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell preparations will be generated. Myeloma cells will be isolated and frozen for subsequent vaccine generation for patients randomized to the vaccine arm (randomization occurs after transplant and recovery). Autologous Stem Cell Transplant: Patients will receive an autologous graft with a minimum cell dose of 2.0 x 10^6 CD34+ cells/kg patient actual body weight per autologous transplantation. Melphalan: Autologous hematopoietic cell transplant will be done with high-dose melphalan of 200mg/m^2 at the schedule and timing according to institutional practices. Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy. GM-CSF: 100 ug GM-CSF will be given subcutaneously in the upper thigh and daily for a total of 4 days of each cycle.	Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will receive maintenance lenalidomide. Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell preparations will be generated. Myeloma cells will be isolated and frozen for subsequent vaccine generation for patients randomized to the vaccine arm (randomization occurs after transplant and recovery). Autologous Stem Cell Transplant: Patients will receive an autologous graft with a minimum cell dose of 2.0 x 10^6 CD34+ cells/kg patient actual body weight per autologous transplantation. Melphalan: Autologous hematopoietic cell transplant will be done with high-dose melphalan of 200mg/m^2 at the schedule and timing according to institutional practices. Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy.
Measure Participants	68	37	35
Number (95% Confidence Interval) [percentage of participants]	20.7 30.4%	8.7 23.5%	15.1 43.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lenalidomide, Vaccine, and GM-CSF, Lenalidomide With or Without GM-CSF
	Comments	The null hypothesis is that there is no difference of Myeloma Progression between the vaccine arm and lenalidomide/GM-CSF arm.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.116
	Comments	Statistical significance was determined using a pre-specified threshold of 0.05
	Method	Gray's test for cumulative Incidence
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Lenalidomide, Vaccine, and GM-CSF, Maintenance Lenalidomide
	Comments	The null hypothesis is that there is no difference of Myeloma Progression between the vaccine arm and lenalidomide alone arm.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.519
	Comments	Statistical significance was determined using a pre-specified threshold of 0.05
	Method	Gray's test for cumulative Incidence
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Lenalidomide With or Without GM-CSF, Maintenance Lenalidomide
	Comments	The null hypothesis is that there is no difference of Myeloma Progression between the lenalidomide/GM-CSF arm and lenalidomide alone arm.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.387
	Comments	Statistical significance was determined using a pre-specified threshold of 0.05
	Method	Gray's test for cumulative Incidence
	Comments

5. Secondary Outcome

Title	Percentage of Participants With Treatment-related Mortality (TRM)
Description	TRM is defined as death occurring in a patient from causes other than disease relapse or progression. Disease progression is the competing event for TRM. Patients alive without disease progression at last contact are considered censored for this event. TRM from time of randomization will be compared between vaccine and no-vaccine arms combined starting at time of randomization.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description
The randomized participants are included in the analysis

Arm/Group Title	Lenalidomide, Vaccine, and GM-CSF	Lenalidomide With or Without GM-CSF
Arm/Group Description	Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will undergo leukapheresis and then will receive maintenance lenalidomide with myeloma vaccine and GM-CSF. Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell will be isolated and frozen for subsequent vaccine generation. Autologous Stem Cell Transplant: Patients will receive an autologous graft of a minimum cell dose of 2.0 x 10^6 CD34+ cells/kg patient actual body weight per transplantation with high-dose melphalan of 200mg/m^2 at the schedule and timing according to institutional practices. Leukapheresis: Blood samples will be collected through a catheter in the neck or chest and leukapheresis will be performed using standard clinical procedures. Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy. Myeloma vaccine: The target dose is 3 x 10^6 fusion cells per vaccine. A minimum of 3 x 10^6 total fusion cells will be required to proceed with vaccine administration. Patients will receive the DC/MM fusion vaccine on day 1 of cycles 2, 3, and 4 of lenalidomide maintenance. GM-CSF: 100 ug GM-CSF will be given for a total of 4 days of each cycle.	Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will receive maintenance lenalidomide with or without GM-CSF. Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell preparations will be generated. Myeloma cells will be isolated and frozen for subsequent vaccine generation for patients randomized to the vaccine arm (randomization occurs after transplant and recovery). Autologous Stem Cell Transplant: Patients will receive an autologous graft with a minimum cell dose of 2.0 x 10^6 CD34+ cells/kg patient actual body weight per autologous transplantation. Melphalan: Autologous hematopoietic cell transplant will be done with high-dose melphalan of 200mg/m^2 at the schedule and timing according to institutional practices. Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy. GM-CSF: 100 ug GM-CSF will be given subcutaneously in the upper thigh and daily for a total of 4 days of each cycle.
Measure Participants	68	72
Number (95% Confidence Interval) [percentage of participants]	0 0%	0 0%

6. Secondary Outcome

Title	Percentage of Participants With Progression-Free Survival
Description	Death or disease progression will be considered as events for this endpoint. The time to event will be calculated as time from randomization to disease progression, death, initiation of non-protocol anti-myeloma therapy, loss to follow-up or the end of the study, whichever comes first. The Kaplan-Meier estimator will be constructed for each treatment arm. Progression-free survival was compared between the vaccine and the combined non-vaccine arms using the log-rank test.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description
The randomized participants are included in the analysis

Arm/Group Title	Lenalidomide, Vaccine, and GM-CSF	Lenalidomide With or Without GM-CSF
Arm/Group Description	Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will undergo leukapheresis and then will receive maintenance lenalidomide with myeloma vaccine and GM-CSF. Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell will be isolated and frozen for subsequent vaccine generation. Autologous Stem Cell Transplant: Patients will receive an autologous graft of a minimum cell dose of 2.0 x 10^6 CD34+ cells/kg patient actual body weight per transplantation with high-dose melphalan of 200mg/m^2 at the schedule and timing according to institutional practices. Leukapheresis: Blood samples will be collected through a catheter in the neck or chest and leukapheresis will be performed using standard clinical procedures. Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy. Myeloma vaccine: The target dose is 3 x 10^6 fusion cells per vaccine. A minimum of 3 x 10^6 total fusion cells will be required to proceed with vaccine administration. Patients will receive the DC/MM fusion vaccine on day 1 of cycles 2, 3, and 4 of lenalidomide maintenance. GM-CSF: 100 ug GM-CSF will be given for a total of 4 days of each cycle.	Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will receive maintenance lenalidomide with or without GM-CSF. Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell preparations will be generated. Myeloma cells will be isolated and frozen for subsequent vaccine generation for patients randomized to the vaccine arm (randomization occurs after transplant and recovery). Autologous Stem Cell Transplant: Patients will receive an autologous graft with a minimum cell dose of 2.0 x 10^6 CD34+ cells/kg patient actual body weight per autologous transplantation. Melphalan: Autologous hematopoietic cell transplant will be done with high-dose melphalan of 200mg/m^2 at the schedule and timing according to institutional practices. Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy. GM-CSF: 100 ug GM-CSF will be given subcutaneously in the upper thigh and daily for a total of 4 days of each cycle.
Measure Participants	68	72
Number (95% Confidence Interval) [percentage of participants]	79.3 116.6%	88.2 238.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lenalidomide, Vaccine, and GM-CSF, Lenalidomide With or Without GM-CSF
	Comments	The null hypothesis is that there is no difference of Progression-Free Survival between vaccine vs. non- vaccine arms.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.168
	Comments	Statistical significance was determined using a pre-specified threshold of 0.05
	Method	Log Rank
	Comments

7. Secondary Outcome

Title	Percentage of Participants With Progression-Free Survival in Pairwise Analysis
Description	This is the pairwise comparison for percentage of participants with Progression-Free Survival. Death or disease progression will be considered as events for this endpoint. The time to event will be calculated as time from randomization to disease progression, death, initiation of non-protocol anti-myeloma therapy, loss to follow-up or the end of the study, whichever comes first. The Kaplan-Meier estimator will be constructed for each treatment arm. Progression-free survival was compared between the vaccine arm, lenalidomide/GM-CSF arm and lenalidomide alone arm.
Time Frame	2 year

Outcome Measure Data

Analysis Population Description
The randomized participants are included in the analysis

Arm/Group Title	Lenalidomide, Vaccine, and GM-CSF	Lenalidomide and GM-CSF	Maintenance Lenalidomide
Arm/Group Description	Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will undergo leukapheresis and then will receive maintenance lenalidomide with myeloma vaccine and GM-CSF. Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell will be isolated and frozen for subsequent vaccine generation. Autologous Stem Cell Transplant: Patients will receive an autologous graft of a minimum cell dose of 2.0 x 10^6 CD34+ cells/kg patient actual body weight per transplantation with high-dose melphalan of 200mg/m^2 at the schedule and timing according to institutional practices. Leukapheresis: Blood samples will be collected through a catheter in the neck or chest and leukapheresis will be performed using standard clinical procedures. Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy. Myeloma vaccine: The target dose is 3 x 10^6 fusion cells per vaccine. A minimum of 3 x 10^6 total fusion cells will be required to proceed with vaccine administration. Patients will receive the DC/MM fusion vaccine on day 1 of cycles 2, 3, and 4 of lenalidomide maintenance. GM-CSF: 100 ug GM-CSF will be given for a total of 4 days of each cycle.	Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will receive maintenance lenalidomide with GM-CSF. Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell preparations will be generated. Myeloma cells will be isolated and frozen for subsequent vaccine generation for patients randomized to the vaccine arm (randomization occurs after transplant and recovery). Autologous Stem Cell Transplant: Patients will receive an autologous graft with a minimum cell dose of 2.0 x 10^6 CD34+ cells/kg patient actual body weight per autologous transplantation. Melphalan: Autologous hematopoietic cell transplant will be done with high-dose melphalan of 200mg/m^2 at the schedule and timing according to institutional practices. Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy. GM-CSF: 100 ug GM-CSF will be given subcutaneously in the upper thigh and daily for a total of 4 days of each cycle.	Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will receive maintenance lenalidomide. Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell preparations will be generated. Myeloma cells will be isolated and frozen for subsequent vaccine generation for patients randomized to the vaccine arm (randomization occurs after transplant and recovery). Autologous Stem Cell Transplant: Patients will receive an autologous graft with a minimum cell dose of 2.0 x 10^6 CD34+ cells/kg patient actual body weight per autologous transplantation. Melphalan: Autologous hematopoietic cell transplant will be done with high-dose melphalan of 200mg/m^2 at the schedule and timing according to institutional practices. Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy.
Measure Participants	68	37	35
Number (95% Confidence Interval) [percentage of participants]	79.3 116.6%	91.3 246.8%	84.9 242.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lenalidomide, Vaccine, and GM-CSF, Lenalidomide With or Without GM-CSF
	Comments	The null hypothesis is that there is no difference of Progression-Free Survival between the vaccine arm and lenalidomide/GM-CSF arm.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.120
	Comments	Statistical significance was determined using a pre-specified threshold of 0.05
	Method	Log Rank
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Lenalidomide, Vaccine, and GM-CSF, Maintenance Lenalidomide
	Comments	The null hypothesis is that there is no difference of Progression-Free Survival between the vaccine arm and lenalidomide alone arm.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.519
	Comments	Statistical significance was determined using a pre-specified threshold of 0.05
	Method	Log Rank
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Lenalidomide With or Without GM-CSF, Maintenance Lenalidomide
	Comments	The null hypothesis is that there is no difference of Progression-Free Survival between the lenalidomide/GM-CSF arm and lenalidomide alone arm.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.387
	Comments	Statistical significance was determined using a pre-specified threshold of 0.05
	Method	Log Rank
	Comments

8. Secondary Outcome

Title	Percentage of Participants With Overall Survival
Description	Death from any cause is considered as events for this endpoint. The time to event is calculated as time from randomization to death, loss to follow-up or the end of the study, whichever comes first. Patients alive at the time of last observation are considered censored. The Kaplan-Meier estimator will be constructed for each treatment arm. Overall survival are compared between the vaccine and the combined non-vaccine arms from time of randomization.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description
The randomized participants are included in the analysis

Arm/Group Title	Lenalidomide, Vaccine, and GM-CSF	Lenalidomide With or Without GM-CSF
Arm/Group Description	Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will undergo leukapheresis and then will receive maintenance lenalidomide with myeloma vaccine and GM-CSF. Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell will be isolated and frozen for subsequent vaccine generation. Autologous Stem Cell Transplant: Patients will receive an autologous graft of a minimum cell dose of 2.0 x 10^6 CD34+ cells/kg patient actual body weight per transplantation with high-dose melphalan of 200mg/m^2 at the schedule and timing according to institutional practices. Leukapheresis: Blood samples will be collected through a catheter in the neck or chest and leukapheresis will be performed using standard clinical procedures. Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy. Myeloma vaccine: The target dose is 3 x 10^6 fusion cells per vaccine. A minimum of 3 x 10^6 total fusion cells will be required to proceed with vaccine administration. Patients will receive the DC/MM fusion vaccine on day 1 of cycles 2, 3, and 4 of lenalidomide maintenance. GM-CSF: 100 ug GM-CSF will be given for a total of 4 days of each cycle.	Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will receive maintenance lenalidomide with or without GM-CSF. Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell preparations will be generated. Myeloma cells will be isolated and frozen for subsequent vaccine generation for patients randomized to the vaccine arm (randomization occurs after transplant and recovery). Autologous Stem Cell Transplant: Patients will receive an autologous graft with a minimum cell dose of 2.0 x 10^6 CD34+ cells/kg patient actual body weight per autologous transplantation. Melphalan: Autologous hematopoietic cell transplant will be done with high-dose melphalan of 200mg/m^2 at the schedule and timing according to institutional practices. Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy. GM-CSF: 100 ug GM-CSF will be given subcutaneously in the upper thigh and daily for a total of 4 days of each cycle.
Measure Participants	68	72
Number (95% Confidence Interval) [percentage of participants]	97 142.6%	98.5 266.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lenalidomide, Vaccine, and GM-CSF, Lenalidomide With or Without GM-CSF
	Comments	The null hypothesis is that there is no difference of overall Survival between vaccine vs. non- vaccine arms.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.563
	Comments	Statistical significance was determined using a pre-specified threshold of 0.05
	Method	Log Rank
	Comments

9. Secondary Outcome

Title	Percentage of Participants With Overall Survival in Pairwise Analysis
Description	This is the pairwise comparison for percentage of participants with Overall Survival. Death from any cause is considered as events for this endpoint. The time to event is calculated as time from randomization to death, loss to follow-up or the end of the study, whichever comes first. Patients alive at the time of last observation are considered censored. The Kaplan-Meier estimator will be constructed for each treatment arm. Overall survival are compared between the vaccine arm, lenalidomide/GM-CSF arm and lenalidomide alone arm from time of randomization.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description
The randomized participants are included in the analysis

Arm/Group Title	Lenalidomide, Vaccine, and GM-CSF	Lenalidomide and GM-CSF	Maintenance Lenalidomide
Arm/Group Description	Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will undergo leukapheresis and then will receive maintenance lenalidomide with myeloma vaccine and GM-CSF. Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell will be isolated and frozen for subsequent vaccine generation. Autologous Stem Cell Transplant: Patients will receive an autologous graft of a minimum cell dose of 2.0 x 10^6 CD34+ cells/kg patient actual body weight per transplantation with high-dose melphalan of 200mg/m^2 at the schedule and timing according to institutional practices. Leukapheresis: Blood samples will be collected through a catheter in the neck or chest and leukapheresis will be performed using standard clinical procedures. Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy. Myeloma vaccine: The target dose is 3 x 10^6 fusion cells per vaccine. A minimum of 3 x 10^6 total fusion cells will be required to proceed with vaccine administration. Patients will receive the DC/MM fusion vaccine on day 1 of cycles 2, 3, and 4 of lenalidomide maintenance. GM-CSF: 100 ug GM-CSF will be given for a total of 4 days of each cycle.	Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will receive maintenance lenalidomide with GM-CSF. Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell preparations will be generated. Myeloma cells will be isolated and frozen for subsequent vaccine generation for patients randomized to the vaccine arm (randomization occurs after transplant and recovery). Autologous Stem Cell Transplant: Patients will receive an autologous graft with a minimum cell dose of 2.0 x 10^6 CD34+ cells/kg patient actual body weight per autologous transplantation. Melphalan: Autologous hematopoietic cell transplant will be done with high-dose melphalan of 200mg/m^2 at the schedule and timing according to institutional practices. Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy. GM-CSF: 100 ug GM-CSF will be given subcutaneously in the upper thigh and daily for a total of 4 days of each cycle.	Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will receive maintenance lenalidomide. Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell preparations will be generated. Myeloma cells will be isolated and frozen for subsequent vaccine generation for patients randomized to the vaccine arm (randomization occurs after transplant and recovery). Autologous Stem Cell Transplant: Patients will receive an autologous graft with a minimum cell dose of 2.0 x 10^6 CD34+ cells/kg patient actual body weight per autologous transplantation. Melphalan: Autologous hematopoietic cell transplant will be done with high-dose melphalan of 200mg/m^2 at the schedule and timing according to institutional practices. Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy.
Measure Participants	68	37	35
Number (95% Confidence Interval) [percentage of participants]	97 142.6%	100 270.3%	96.9 276.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lenalidomide, Vaccine, and GM-CSF, Lenalidomide With or Without GM-CSF
	Comments	The null hypothesis is that there is no difference of overall Survival between the vaccine arm and lenalidomide/GM-CSF arm.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.308
	Comments	Statistical significance was determined using a pre-specified threshold of 0.05
	Method	Log Rank
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Lenalidomide, Vaccine, and GM-CSF, Maintenance Lenalidomide
	Comments	The null hypothesis is that there is no difference of overall Survival between the vaccine arm and lenalidomide alone arm.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.990
	Comments	Statistical significance was determined using a pre-specified threshold of 0.05
	Method	Log Rank
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Lenalidomide With or Without GM-CSF, Maintenance Lenalidomide
	Comments	The null hypothesis is that there is no difference of overall Survival between the lenalidomide/GM-CSF arm and lenalidomide alone arm.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.303
	Comments	Statistical significance was determined using a pre-specified threshold of 0.05
	Method	Log Rank
	Comments

10. Secondary Outcome

Title	Number of Grade ≥ 3 Toxicities
Description	Toxicities are evaluated using NCI CTCAE version 4.0 at pre-maintenance initiation and during maintenance therapy monthly for the first 4 cycles and then at cycles 6, 9, 15, 21, 24, which correspond to Day 1, 29, 57, 85, 141, 225, 393, 561, and 645 post maintenance initiation. All Grade ≥ 3 toxicities will be tabulated for treatment arms. Toxicities are categorized by organ system according to the CTCAE. Toxicities that involve multiple questions per organ system are combined in one category.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description
The randomized participants are included in the analysis

Arm/Group Title	Lenalidomide, Vaccine, and GM-CSF	Lenalidomide and GM-CSF	Maintenance Lenalidomide
Arm/Group Description	Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will undergo leukapheresis and then will receive maintenance lenalidomide with myeloma vaccine and GM-CSF. Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell will be isolated and frozen for subsequent vaccine generation. Autologous Stem Cell Transplant: Patients will receive an autologous graft of a minimum cell dose of 2.0 x 10^6 CD34+ cells/kg patient actual body weight per transplantation with high-dose melphalan of 200mg/m^2 at the schedule and timing according to institutional practices. Leukapheresis: Blood samples will be collected through a catheter in the neck or chest and leukapheresis will be performed using standard clinical procedures. Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy. Myeloma vaccine: The target dose is 3 x 10^6 fusion cells per vaccine. A minimum of 3 x 10^6 total fusion cells will be required to proceed with vaccine administration. Patients will receive the DC/MM fusion vaccine on day 1 of cycles 2, 3, and 4 of lenalidomide maintenance. GM-CSF: 100 ug GM-CSF will be given for a total of 4 days of each cycle.	Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will receive maintenance lenalidomide with GM-CSF. Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell preparations will be generated. Myeloma cells will be isolated and frozen for subsequent vaccine generation for patients randomized to the vaccine arm (randomization occurs after transplant and recovery). Autologous Stem Cell Transplant: Patients will receive an autologous graft with a minimum cell dose of 2.0 x 10^6 CD34+ cells/kg patient actual body weight per autologous transplantation. Melphalan: Autologous hematopoietic cell transplant will be done with high-dose melphalan of 200mg/m^2 at the schedule and timing according to institutional practices. Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy. GM-CSF: 100 ug GM-CSF will be given subcutaneously in the upper thigh and daily for a total of 4 days of each cycle.	Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will receive maintenance lenalidomide. Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell preparations will be generated. Myeloma cells will be isolated and frozen for subsequent vaccine generation for patients randomized to the vaccine arm (randomization occurs after transplant and recovery). Autologous Stem Cell Transplant: Patients will receive an autologous graft with a minimum cell dose of 2.0 x 10^6 CD34+ cells/kg patient actual body weight per autologous transplantation. Melphalan: Autologous hematopoietic cell transplant will be done with high-dose melphalan of 200mg/m^2 at the schedule and timing according to institutional practices. Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy.
Measure Participants	68	37	35
Auditory Disorders	1	0	0
Blood and Lymphatic Disorders	81	40	38
Cardiovascular Disorders	4	3	2
GI Disorders	15	4	2
General Disorders	5	2	2
Hepatobiliary/Pancreas Disorders	4	1	1
Immune System Disorders	2	0	0
Investigations	2	0	1
Metabolism and Nutrition Disorders	7	1	3
Musculoskeletal and Connective Tissue Disorders	1	1	2
Nervous System Disorders	14	5	1
Renal Disorders	1	0	2
Respiratory, Thoracic and Mediastinal Disorders	5	1	2
Skin and Subcutaneous Tissue Disorders	4	5	7
Vascular Disorders	6	11	3
Abnormal Liver Symptoms	0	1	0

11. Secondary Outcome

Title	Participants With Grade ≥ 3 Toxicities
Description	Toxicities are evaluated using NCI CTCAE version 4.0 at pre-maintenance initiation and during maintenance therapy monthly for the first 4 cycles and then at cycles 6, 9, 15, 21, 24, which correspond to Day 1, 29, 57, 85, 141, 225, 393, 561, and 645 post maintenance initiation. The number of participants experiencing Grade ≥ 3 toxicity are displayed for the vaccine and non-vaccine arms separately. The proportion of participants experiencing Grade ≥ 3 toxicity are compared between the vaccine and non-vaccine arms combined.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description
The randomized participants are included in the analysis

Arm/Group Title	Lenalidomide, Vaccine, and GM-CSF	Lenalidomide With or Without GM-CSF
Arm/Group Description	Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will undergo leukapheresis and then will receive maintenance lenalidomide with myeloma vaccine and GM-CSF. Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell will be isolated and frozen for subsequent vaccine generation. Autologous Stem Cell Transplant: Patients will receive an autologous graft of a minimum cell dose of 2.0 x 10^6 CD34+ cells/kg patient actual body weight per transplantation with high-dose melphalan of 200mg/m^2 at the schedule and timing according to institutional practices. Leukapheresis: Blood samples will be collected through a catheter in the neck or chest and leukapheresis will be performed using standard clinical procedures. Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy. Myeloma vaccine: The target dose is 3 x 10^6 fusion cells per vaccine. A minimum of 3 x 10^6 total fusion cells will be required to proceed with vaccine administration. Patients will receive the DC/MM fusion vaccine on day 1 of cycles 2, 3, and 4 of lenalidomide maintenance. GM-CSF: 100 ug GM-CSF will be given for a total of 4 days of each cycle.	Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will receive maintenance lenalidomide with or without GM-CSF. Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell preparations will be generated. Myeloma cells will be isolated and frozen for subsequent vaccine generation for patients randomized to the vaccine arm (randomization occurs after transplant and recovery). Autologous Stem Cell Transplant: Patients will receive an autologous graft with a minimum cell dose of 2.0 x 10^6 CD34+ cells/kg patient actual body weight per autologous transplantation. Melphalan: Autologous hematopoietic cell transplant will be done with high-dose melphalan of 200mg/m^2 at the schedule and timing according to institutional practices. Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy. GM-CSF: 100 ug GM-CSF will be given subcutaneously in the upper thigh and daily for a total of 4 days of each cycle.
Measure Participants	68	72
Count of Participants [Participants]	53 77.9%	49 132.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lenalidomide, Vaccine, and GM-CSF, Lenalidomide With or Without GM-CSF
	Comments	The null hypothesis is that there is no difference of proportions of patients With Grade ≥ 3 Toxicities between vaccine vs. non- vaccine arms.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.189
	Comments	Statistical significance was determined using a pre-specified threshold of 0.05
	Method	Chi-squared
	Comments

12. Secondary Outcome

Title	Number of Grade 2 and 3 Infections
Description	Grade 2 and 3 infections, as defined by the BMT CTN Technical MOP, occurring after randomization will be reported. The incidence of definite and probable viral, fungal and bacterial infections will be tabulated for each patient.
Time Frame	2years

Outcome Measure Data

Analysis Population Description
The randomized participants are included in the analysis

Arm/Group Title	Lenalidomide, Vaccine, and GM-CSF	Lenalidomide and GM-CSF	Maintenance Lenalidomide
Arm/Group Description	Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will undergo leukapheresis and then will receive maintenance lenalidomide with myeloma vaccine and GM-CSF. Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell will be isolated and frozen for subsequent vaccine generation. Autologous Stem Cell Transplant: Patients will receive an autologous graft of a minimum cell dose of 2.0 x 10^6 CD34+ cells/kg patient actual body weight per transplantation with high-dose melphalan of 200mg/m^2 at the schedule and timing according to institutional practices. Leukapheresis: Blood samples will be collected through a catheter in the neck or chest and leukapheresis will be performed using standard clinical procedures. Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy. Myeloma vaccine: The target dose is 3 x 10^6 fusion cells per vaccine. A minimum of 3 x 10^6 total fusion cells will be required to proceed with vaccine administration. Patients will receive the DC/MM fusion vaccine on day 1 of cycles 2, 3, and 4 of lenalidomide maintenance. GM-CSF: 100 ug GM-CSF will be given for a total of 4 days of each cycle.	Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will receive maintenance lenalidomide with GM-CSF. Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell preparations will be generated. Myeloma cells will be isolated and frozen for subsequent vaccine generation for patients randomized to the vaccine arm (randomization occurs after transplant and recovery). Autologous Stem Cell Transplant: Patients will receive an autologous graft with a minimum cell dose of 2.0 x 10^6 CD34+ cells/kg patient actual body weight per autologous transplantation. Melphalan: Autologous hematopoietic cell transplant will be done with high-dose melphalan of 200mg/m^2 at the schedule and timing according to institutional practices. Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy. GM-CSF: 100 ug GM-CSF will be given subcutaneously in the upper thigh and daily for a total of 4 days of each cycle.	Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will receive maintenance lenalidomide. Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell preparations will be generated. Myeloma cells will be isolated and frozen for subsequent vaccine generation for patients randomized to the vaccine arm (randomization occurs after transplant and recovery). Autologous Stem Cell Transplant: Patients will receive an autologous graft with a minimum cell dose of 2.0 x 10^6 CD34+ cells/kg patient actual body weight per autologous transplantation. Melphalan: Autologous hematopoietic cell transplant will be done with high-dose melphalan of 200mg/m^2 at the schedule and timing according to institutional practices. Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy.
Measure Participants	68	37	35
Bacterial	10	3	6
Viral	14	6	14
Fungal	0	0	0
Other	1	0	1

13. Secondary Outcome

Title	Percentage of Participants With Grade 2 and 3 Infections
Description	Grade 2 and 3 infections, as defined by the BMT CTN Technical MOP, are reported on the study. The cumulative incidence of infections post randomization, treating death as a competing risk, were compared between the vaccine and the combined non-vaccine groups using the Gray's test.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description
The randomized participants are included in the analysis

Arm/Group Title	Lenalidomide, Vaccine, and GM-CSF	Lenalidomide With or Without GM-CSF
Arm/Group Description	Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will undergo leukapheresis and then will receive maintenance lenalidomide with myeloma vaccine and GM-CSF. Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell will be isolated and frozen for subsequent vaccine generation. Autologous Stem Cell Transplant: Patients will receive an autologous graft of a minimum cell dose of 2.0 x 10^6 CD34+ cells/kg patient actual body weight per transplantation with high-dose melphalan of 200mg/m^2 at the schedule and timing according to institutional practices. Leukapheresis: Blood samples will be collected through a catheter in the neck or chest and leukapheresis will be performed using standard clinical procedures. Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy. Myeloma vaccine: The target dose is 3 x 10^6 fusion cells per vaccine. A minimum of 3 x 10^6 total fusion cells will be required to proceed with vaccine administration. Patients will receive the DC/MM fusion vaccine on day 1 of cycles 2, 3, and 4 of lenalidomide maintenance. GM-CSF: 100 ug GM-CSF will be given for a total of 4 days of each cycle.	Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will receive maintenance lenalidomide with or without GM-CSF. Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell preparations will be generated. Myeloma cells will be isolated and frozen for subsequent vaccine generation for patients randomized to the vaccine arm (randomization occurs after transplant and recovery). Autologous Stem Cell Transplant: Patients will receive an autologous graft with a minimum cell dose of 2.0 x 10^6 CD34+ cells/kg patient actual body weight per autologous transplantation. Melphalan: Autologous hematopoietic cell transplant will be done with high-dose melphalan of 200mg/m^2 at the schedule and timing according to institutional practices. Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy. GM-CSF: 100 ug GM-CSF will be given subcutaneously in the upper thigh and daily for a total of 4 days of each cycle.
Measure Participants	68	72
Number (95% Confidence Interval) [percentage of participants]	26.6 39.1%	23.2 62.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lenalidomide, Vaccine, and GM-CSF, Lenalidomide With or Without GM-CSF
	Comments	The null hypothesis is that there is no difference of Participants with Grade 2 and 3 infections between vaccine vs. non- vaccine arms.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.82
	Comments	Statistical significance was determined using a pre-specified threshold of 0.05
	Method	Gray's test for cumulative Incidence
	Comments

14. Secondary Outcome

Title	Percentage of Participants With Grade 2 and 3 Infections in Pairwise Analysis
Description	This is the pairwise comparison for percentage of participants with Grade 2 and 3 infections. Grade 2 and 3 infections, as defined by the BMT CTN Technical MOP, are reported on the study. The cumulative incidence of infections post randomization, treating death as a competing risk, were compared between the vaccine arm, lenalidomide/GM-CSF arm and lenalidomide alone arm using the Gray's test.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description
The randomized participants are included in the analysis

Arm/Group Title	Lenalidomide, Vaccine, and GM-CSF	Lenalidomide and GM-CSF	Maintenance Lenalidomide
Arm/Group Description	Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will undergo leukapheresis and then will receive maintenance lenalidomide with myeloma vaccine and GM-CSF. Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell will be isolated and frozen for subsequent vaccine generation. Autologous Stem Cell Transplant: Patients will receive an autologous graft of a minimum cell dose of 2.0 x 10^6 CD34+ cells/kg patient actual body weight per transplantation with high-dose melphalan of 200mg/m^2 at the schedule and timing according to institutional practices. Leukapheresis: Blood samples will be collected through a catheter in the neck or chest and leukapheresis will be performed using standard clinical procedures. Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy. Myeloma vaccine: The target dose is 3 x 10^6 fusion cells per vaccine. A minimum of 3 x 10^6 total fusion cells will be required to proceed with vaccine administration. Patients will receive the DC/MM fusion vaccine on day 1 of cycles 2, 3, and 4 of lenalidomide maintenance. GM-CSF: 100 ug GM-CSF will be given for a total of 4 days of each cycle.	Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will receive maintenance lenalidomide with GM-CSF. Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell preparations will be generated. Myeloma cells will be isolated and frozen for subsequent vaccine generation for patients randomized to the vaccine arm (randomization occurs after transplant and recovery). Autologous Stem Cell Transplant: Patients will receive an autologous graft with a minimum cell dose of 2.0 x 10^6 CD34+ cells/kg patient actual body weight per autologous transplantation. Melphalan: Autologous hematopoietic cell transplant will be done with high-dose melphalan of 200mg/m^2 at the schedule and timing according to institutional practices. Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy. GM-CSF: 100 ug GM-CSF will be given subcutaneously in the upper thigh and daily for a total of 4 days of each cycle.	Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will receive maintenance lenalidomide. Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell preparations will be generated. Myeloma cells will be isolated and frozen for subsequent vaccine generation for patients randomized to the vaccine arm (randomization occurs after transplant and recovery). Autologous Stem Cell Transplant: Patients will receive an autologous graft with a minimum cell dose of 2.0 x 10^6 CD34+ cells/kg patient actual body weight per autologous transplantation. Melphalan: Autologous hematopoietic cell transplant will be done with high-dose melphalan of 200mg/m^2 at the schedule and timing according to institutional practices. Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy.
Measure Participants	68	37	35
Number (95% Confidence Interval) [percentage of participants]	26.6 39.1%	14.2 38.4%	32.6 93.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lenalidomide, Vaccine, and GM-CSF, Lenalidomide With or Without GM-CSF
	Comments	The null hypothesis is that there is no difference of Participants with Grade 2 and 3 infections between the vaccine arm and lenalidomide/GM-CSF arm.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.21
	Comments	Statistical significance was determined using a pre-specified threshold of 0.05
	Method	Gray's test for cumulative Incidence
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Lenalidomide, Vaccine, and GM-CSF, Maintenance Lenalidomide
	Comments	The null hypothesis is that there is no difference of Participants with Grade 2 and 3 infections between the vaccine arm and lenalidomide alone arm.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.40
	Comments	Statistical significance was determined using a pre-specified threshold of 0.05
	Method	Gray's test for cumulative Incidence
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Lenalidomide With or Without GM-CSF, Maintenance Lenalidomide
	Comments	The null hypothesis is that there is no difference of Participants with Grade 2 and 3 infections between the lenalidomide/GM-CSF arm and lenalidomide alone arm.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.08
	Comments	Statistical significance was determined using a pre-specified threshold of 0.05
	Method	Gray's test for cumulative Incidence
	Comments

15. Secondary Outcome

Title	Number of Participants With Minimal Residual Disease (MRD)
Description	Minimal residual disease (MRD) is defined as the presence of malignant plasma cells detected by multicolor flow cytometry among patients who are in complete remission. Multichannel flow cytometry will be used to establish MRD based on the presence of malignant plasma cells that are CD45 (-/dim), CD38+, CD138+, CD19-, CD56+ kappa or lambda restricted. The number of patients with MRD negative (MRD-) are described using frequencies at pre-randomization and 9th cycle post-randomization and compared between the vaccine arm with the no-vaccine arms combined.
Time Frame	Pre-randomization, Post-randomization at Cycle 9

Outcome Measure Data

Analysis Population Description
The randomized participants who had MRD assessment. Participants who did not have MRD assessment are not included in this analysis.

Arm/Group Title	Lenalidomide, Vaccine, and GM-CSF	Lenalidomide With or Without GM-CSF
Arm/Group Description	Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will undergo leukapheresis and then will receive maintenance lenalidomide with myeloma vaccine and GM-CSF. Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell will be isolated and frozen for subsequent vaccine generation. Autologous Stem Cell Transplant: Patients will receive an autologous graft of a minimum cell dose of 2.0 x 10^6 CD34+ cells/kg patient actual body weight per transplantation with high-dose melphalan of 200mg/m^2 at the schedule and timing according to institutional practices. Leukapheresis: Blood samples will be collected through a catheter in the neck or chest and leukapheresis will be performed using standard clinical procedures. Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy. Myeloma vaccine: The target dose is 3 x 10^6 fusion cells per vaccine. A minimum of 3 x 10^6 total fusion cells will be required to proceed with vaccine administration. Patients will receive the DC/MM fusion vaccine on day 1 of cycles 2, 3, and 4 of lenalidomide maintenance. GM-CSF: 100 ug GM-CSF will be given for a total of 4 days of each cycle.	Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will receive maintenance lenalidomide with or without GM-CSF. Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell preparations will be generated. Myeloma cells will be isolated and frozen for subsequent vaccine generation for patients randomized to the vaccine arm (randomization occurs after transplant and recovery). Autologous Stem Cell Transplant: Patients will receive an autologous graft with a minimum cell dose of 2.0 x 10^6 CD34+ cells/kg patient actual body weight per autologous transplantation. Melphalan: Autologous hematopoietic cell transplant will be done with high-dose melphalan of 200mg/m^2 at the schedule and timing according to institutional practices. Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy. GM-CSF: 100 ug GM-CSF will be given subcutaneously in the upper thigh and daily for a total of 4 days of each cycle.
Measure Participants	65	66
Pre-randomization	35 51.5%	31 83.8%
Post-randomization at Cycle 9	38 55.9%	41 110.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Lenalidomide, Vaccine, and GM-CSF, Lenalidomide With or Without GM-CSF
	Comments	The null hypothesis is that there is no difference of proportions of patients without Minimal Residual Disease between vaccine vs. non- vaccine arms
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.80
	Comments	Statistical significance was determined using a pre-specified threshold of 0.05.
	Method	Chi-squared
	Comments

Adverse Events

	Lenalidomide, Vaccine, and GM-CSF		Lenalidomide and GM-CSF		Maintenance Lenalidomide
Time Frame	2 years
Adverse Event Reporting Description

Arm/Group Title	Lenalidomide, Vaccine, and GM-CSF		Lenalidomide and GM-CSF		Maintenance Lenalidomide
Arm/Group Description	Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will undergo leukapheresis and then will receive maintenance lenalidomide with myeloma vaccine and GM-CSF. Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell will be isolated and frozen for subsequent vaccine generation. Autologous Stem Cell Transplant: Patients will receive an autologous graft of a minimum cell dose of 2.0 x 10^6 CD34+ cells/kg patient actual body weight per transplantation with high-dose melphalan of 200mg/m^2 at the schedule and timing according to institutional practices. Leukapheresis: Blood samples will be collected through a catheter in the neck or chest and leukapheresis will be performed using standard clinical procedures. Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy. Myeloma vaccine: The target dose is 3 x 10^6 fusion cells per vaccine. A minimum of 3 x 10^6 total fusion cells will be required to proceed with vaccine administration. Patients will receive the DC/MM fusion vaccine on day 1 of cycles 2, 3, and 4 of lenalidomide maintenance. GM-CSF: 100 ug GM-CSF will be given for a total of 4 days of each cycle.		Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will receive maintenance lenalidomide with GM-CSF. Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell preparations will be generated. Myeloma cells will be isolated and frozen for subsequent vaccine generation for patients randomized to the vaccine arm (randomization occurs after transplant and recovery). Autologous Stem Cell Transplant: Patients will receive an autologous graft with a minimum cell dose of 2.0 x 10^6 CD34+ cells/kg patient actual body weight per autologous transplantation. Melphalan: Autologous hematopoietic cell transplant will be done with high-dose melphalan of 200mg/m^2 at the schedule and timing according to institutional practices. Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy. GM-CSF: 100 ug GM-CSF will be given subcutaneously in the upper thigh and daily for a total of 4 days of each cycle.		Patients will undergo tumor cell collection and autologous stem cell transplant with melphalan. Patients will receive maintenance lenalidomide. Tumor Cell Collection: Patients will undergo aspiration of 30 mL of bone marrow from which myeloma cell preparations will be generated. Myeloma cells will be isolated and frozen for subsequent vaccine generation for patients randomized to the vaccine arm (randomization occurs after transplant and recovery). Autologous Stem Cell Transplant: Patients will receive an autologous graft with a minimum cell dose of 2.0 x 10^6 CD34+ cells/kg patient actual body weight per autologous transplantation. Melphalan: Autologous hematopoietic cell transplant will be done with high-dose melphalan of 200mg/m^2 at the schedule and timing according to institutional practices. Lenalidomide: Maintenance therapy with lenalidomide will begin between 90 and 100 days after stem cell infusion. Lenalidomide will be administered initially at a dose of 10 mg per day continuously. Cycle duration during maintenance therapy is 28 days. Patients will continue lenalidomide for two years from initiation of therapy.
All Cause Mortality
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/68 (4.4%)		0/37 (0%)		1/35 (2.9%)
Serious Adverse Events
	Lenalidomide, Vaccine, and GM-CSF		Lenalidomide and GM-CSF		Maintenance Lenalidomide
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/68 (2.9%)		3/37 (8.1%)		1/35 (2.9%)
Blood and lymphatic system disorders
NEUTROPENIC FEVER	1/68 (1.5%)	1	0/37 (0%)	0	0/35 (0%)	0
Cardiac disorders
ATRIAL FLUTTER	0/68 (0%)	0	0/37 (0%)	0	1/35 (2.9%)	1
CONGESTIVE HEART FAILURE	0/68 (0%)	0	1/37 (2.7%)	1	0/35 (0%)	0
Investigations
PROLONGED QTC	1/68 (1.5%)	1	0/37 (0%)	0	0/35 (0%)	0
ELEVATE LIVER ENZYMES	1/68 (1.5%)	1	0/37 (0%)	0	0/35 (0%)	0
LIVER FUNCTION TESTS INCREASED	0/68 (0%)	0	1/37 (2.7%)	1	0/35 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MELANOMA	0/68 (0%)	0	1/37 (2.7%)	1	0/35 (0%)	0
Nervous system disorders
SYNCOPE	1/68 (1.5%)	1	0/37 (0%)	0	0/35 (0%)	0
Other (Not Including Serious) Adverse Events
	Lenalidomide, Vaccine, and GM-CSF		Lenalidomide and GM-CSF		Maintenance Lenalidomide
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/68 (4.4%)		3/37 (8.1%)		3/35 (8.6%)
Cardiac disorders
ATRIAL FIBRILLATION	1/68 (1.5%)	1	0/37 (0%)	0	0/35 (0%)	0
Investigations
ELEVATED ALT	1/68 (1.5%)	1	0/37 (0%)	0	0/35 (0%)	0
INCREASED ALT > 3.0 X ULN	0/68 (0%)	0	0/37 (0%)	0	1/35 (2.9%)	1
ELEVATED LFT	0/68 (0%)	0	0/37 (0%)	0	1/35 (2.9%)	1
GRADE 2 TRANSAMINITIS	0/68 (0%)	0	1/37 (2.7%)	1	0/35 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
LENTIGO MALIGNA	1/68 (1.5%)	1	0/37 (0%)	0	0/35 (0%)	0
PROSTATE CANCER	0/68 (0%)	0	0/37 (0%)	0	1/35 (2.9%)	1
Vascular disorders
GRADE 2 DVT	0/68 (0%)	0	1/37 (2.7%)	1	0/35 (0%)	0
THROMBOEMBOLIC EVENT	0/68 (0%)	0	1/37 (2.7%)	1	0/35 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

Name/Title	Adam Mendizabal, PhD
Organization	The Emmes Company
Phone	301-284-1798
Email	amendizabal@emmes.com

Responsible Party:

National Heart, Lung, and Blood Institute (NHLBI)

ClinicalTrials.gov Identifier:

NCT02728102

Other Study ID Numbers:

BMT CTN 1401
U01HL069294

First Posted:

Apr 5, 2016

Last Update Posted:

Aug 3, 2022

Last Verified:

Jul 1, 2022