Continued, Long-Term Follow-Up and Lenalidomide Maintenance Therapy for Patients on BMT CTN 0702 Protocol (BMT CTN 07LT)

• Sponsor: National Heart, Lung, and Blood Institute (NHLBI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT02322320
• Collaborator: Blood and Marrow Transplant Clinical Trials Network (Other), National Cancer Institute (NCI) (NIH), National Marrow Donor Program (Other)
• Enrollment: 273
• Locations: 42
• Arms: 3
• Actual Duration (Months): 51.2
• Patients Per Site: 6.5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This study is designed to compare long-term outcomes among patients randomized on the BMT CTN 0702 protocol (NCT01109004), "A Trial of Single Autologous Transplant with or without Consolidation Therapy versus Tandem Autologous Transplant with Lenalidomide Maintenance for Patients with Multiple Myeloma". It is hypothesized that use of novel anti-myeloma agents will improve long-term progression-free survival (PFS) after high-dose melphalan followed by autologous hematopoietic cell transplantation (HCT) as compared to a second autologous transplantation.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma	Drug: Lenalidomide	Phase 3

Detailed Description

This study is designed to compare long-term outcomes among patients randomized on the BMT CTN 0702 protocol (NCT01109004). All patients who consent will be followed for death, progression, Second Primary Malignancies (SPMs), and Quality of Life (QOL). Patients who do not consent to the long-term follow-up mechanism or who have experienced progression on the BMT CTN 0702 study will be followed through the standard Center for International Blood and Marrow Transplant Research (CIBMTR) long-term follow-up mechanism. Additionally, patients who are eligible and are willing to continue with lenalidomide as maintenance therapy will be provided lenalidomide free of charge. These patients will continue to receive lenalidomide as maintenance therapy until disease progression or discontinuation due to toxicity, death, or withdrawal from the study. The endpoints assessed will include progression-free survival (PFS), overall survival (OS), event-free survival (EFS), incidence of second primary malignancies (SPM) and health quality of life (QOL).

Study Design

• Study Type: Interventional
• Actual Enrollment: 273 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Continued, Long-Term Follow-Up and Lenalidomide Maintenance Therapy for Patients on BMT CTN 0702 Protocol (BMT CTN #07LT)
• Actual Study Start Date: Mar 1, 2015
• Actual Primary Completion Date: Jun 7, 2019
• Actual Study Completion Date: Jun 7, 2019

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Tandem Auto Transplant Initial autologous transplant followed by a second autologous transplant and lenalidomide maintenance	Drug: Lenalidomide; In BMT CTN 0702, maintenance therapy with lenalidomide started at 10 mg daily for three months and increased to 15 mg daily. The duration of maintenance was three years in all treatment arms. Lenalidomide will be administered initially at the patient's last documented dose prior to discontinuation of BMT CTN 0702 lenalidomide maintenance therapy. Cycle duration is 28 days. Patients will continue lenalidomide until disease progression, or discontinuation due to toxicity, death, or withdrawal from the study.; Other Names: Revlimid™
Active Comparator: RVD Consolidation Initial autologous transplant followed by lenalidomide, bortezomib and dexamethasone (RVD) consolidation and lenalidomide maintenance	Drug: Lenalidomide; In BMT CTN 0702, maintenance therapy with lenalidomide started at 10 mg daily for three months and increased to 15 mg daily. The duration of maintenance was three years in all treatment arms. Lenalidomide will be administered initially at the patient's last documented dose prior to discontinuation of BMT CTN 0702 lenalidomide maintenance therapy. Cycle duration is 28 days. Patients will continue lenalidomide until disease progression, or discontinuation due to toxicity, death, or withdrawal from the study.; Other Names: Revlimid™
Active Comparator: Lenalidomide Maintenance Initial autologous transplant followed by lenalidomide maintenance	Drug: Lenalidomide; In BMT CTN 0702, maintenance therapy with lenalidomide started at 10 mg daily for three months and increased to 15 mg daily. The duration of maintenance was three years in all treatment arms. Lenalidomide will be administered initially at the patient's last documented dose prior to discontinuation of BMT CTN 0702 lenalidomide maintenance therapy. Cycle duration is 28 days. Patients will continue lenalidomide until disease progression, or discontinuation due to toxicity, death, or withdrawal from the study.; Other Names: Revlimid™

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Progression-free Survival (PFS) [5 years post-randomization in BMT CTN 0702]

   This analysis includes all randomized subjects from the BMT CTN 0702 protocol classified according to their randomized treatment assignment (intention-to-treat). Progression-free survival is defined as survival without disease progression or initiation of non-protocol anti-myeloma therapy. To account for loss to follow-up, the Kaplan-Meier estimator was used to estimate progression-free survival during the 5 year post-randomization follow-up period.

Secondary Outcome Measures

1. Percentage of Participants With Overall Survival (OS) [5 years post-randomization in BMT CTN 0702]

   This analysis includes all randomized subjects from the BMT CTN 0702 protocol classified according to their randomized treatment assignment (intention-to-treat). Overall survival is defined as survival of death from any cause. To account for loss to follow-up, the Kaplan-Meier estimator was used to estimate overall survival during the 5 year post-randomization follow-up period.

2. Percentage of Participants With Event-free Survival (EFS) [5 years post-randomization in BMT CTN 0702]

   This analysis includes all randomized subjects from the BMT CTN 0702 protocol classified according to their randomized treatment assignment (intention-to-treat). Event-free survival is defined as survival without disease progression, second primary malignancy, and death. To account for loss to follow-up, the Kaplan-Meier estimator was used to estimate event-free survival during the 5 year post-randomization follow-up period.

3. Percentage of Participants With Secondary Primary Malignancies (SPM) [5 years post-randomization in BMT CTN 0702]

   This analysis includes all randomized subjects from the BMT CTN 0702 protocol classified according to their randomized treatment assignment (intention-to-treat). SPM is defined as development of any second malignancy, excluding non-melanoma skin cancers. To account for loss to follow-up, the Aalen-Johansen estimator was used to estimate the cumulative incidence of SPM during the 5 year post-randomization follow-up period. The development of any SPMs excludes non-melanoma skin cancers. Death without SPMs will be considered a competing risk for this event. The cumulative incidence of SPMs will be compared between treatment arms.

4. Percentage of Participants With Disease Progression [5 years post-randomization in BMT CTN 0702]

   This analysis includes all randomized subjects from BMT CTN 0702, classified by their treatment assignment (intention-to-treat). Disease progression is defined as progression of multiple myeloma, including one or more of the following: Reappearance of serum monoclonal paraprotein at a level >= 0.5 g/dL 24-hour urine protein electrophoresis of at least 200mg paraprotein/24 hours Abnormal free light chain levels of >10 mg/dl, only in patients without measurable paraprotein in serum and urine At least 10% plasma cells in a bone marrow aspirate or trephine biopsy Definite increase in the size of existing bone lesions or soft tissue plasmacytomas Development of new bone lesions or soft tissue plasmacytomas Development of hypercalcemia (corrected serum Ca >11.5 mg/dL or >2.8 mmol/L) not attributable to other causes To account for loss to follow-up, the Aalen-Johansen estimator was used to estimate the cumulative incidence of progression during the follow-up period.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

Patients fulfilling the following criteria will be eligible to provide continued long-term follow-up data as part of this study:

1. Enrolled and randomized on the BMT CTN 0702 protocol.

2. Alive at the completion of BMT CTN 0702 protocol specified follow-up defined as 4 years post-randomization.

3. Patients without evidence of disease progression at the completion of BMT CTN 0702 protocol specified follow up.

4. Signed Informed Consent Form.

5. Patients with the ability to speak English or Spanish are eligible to participate in the HQL component of this trial.

Inclusion Criteria for Optional Long-term Lenalidomide Maintenance Therapy:

Patients fulfilling the following criteria will be eligible to provide continued long-term follow-up data AND receive long-term lenalidomide maintenance therapy as part of this study:

1. Enrolled and randomized to BMT CTN 0702.

2. Completion of 3 years of maintenance therapy on BMT CTN 0702.

3. Registered in the mandatory Revlimid REMS® program (formerly the RevAssist® for Study Participants (RASP) program), and be willing and able to comply with the requirements of the Revlimid REMS® program, including counseling, pregnancy testing, and phone surveys.

4. Signed informed consent form.

5. Patients with the ability to speak English or Spanish are eligible to participate in the HQL component of this trial.

Exclusion Criteria:

Patients who meet any of the following criteria will be ineligible to receive long-term lenalidomide maintenance therapy as part of this study:

1. Patients who have evidence of disease progression prior to enrollment.

2. Patients who were discontinued from BMT CTN 0702 lenalidomide maintenance therapy, for any reason, prior to the completion of the 3 years of 0702 maintenance.

3. Female patients who are pregnant (positive - Beta Human Chorionic Gonadotropin) or breastfeeding.

4. Females of childbearing potential (FCBP) or men who have sexual contact with FCBP unwilling to use contraceptive techniques during the length of lenalidomide maintenance therapy.

5. Patients who experienced thromboembolic events while on full anticoagulation during prior therapy with lenalidomide.

6. Patients unwilling to take Deep Vein Thrombosis (DVT) prophylaxis.

7. Patients who developed a second primary malignancy, excluding non-melanoma skin cancers after initiation of lenalidomide maintenance therapy on BMT CTN 0702.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Arizona Cancer Center	Tucson	Arizona	United States	85724
2	City of Hope National Medical Center	Duarte	California	United States	91010-3000
3	University of California, San Diego Medical Center	La Jolla	California	United States	92093
4	Stanford Hospital and Clinics	Stanford	California	United States	94305
5	Colorado Blood Cancer Institute	Denver	Colorado	United States	80218
6	University of Florida College of Medicine	Gainesville	Florida	United States	32610
7	University of Miami	Miami	Florida	United States	33624
8	H. Lee Moffitt Cancer Center	Tampa	Florida	United States	33624
9	BMT Group of Georgia (Northside Hospital)	Atlanta	Georgia	United States	30342
10	Rush University Medical Center	Chicago	Illinois	United States	60612
11	University of Kansas Hospital	Kansas City	Kansas	United States	66160
12	Louisiana State University Health Sciences Center	Shreveport	Louisiana	United States	71130
13	DFCI, Brigham and Womens Hospital	Boston	Massachusetts	United States	02114
14	University of Michigan Medical Center	Ann Arbor	Michigan	United States	48105-2967
15	Karmanos Cancer Institute/BMT	Detroit	Michigan	United States	48201
16	University of Minnesota	Minneapolis	Minnesota	United States	55455
17	Washington University, Barnes Jewish Hospital	Saint Louis	Missouri	United States	63110
18	University of Nebraska Medical Center	Omaha	Nebraska	United States	68198-7680
19	Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
20	Roswell Park Cancer Center	Buffalo	New York	United States	14263
21	North Shore University Hospital	Lake Success	New York	United States	11042
22	Mount Sinai Medical Center	New York	New York	United States	10029
23	Memorial Sloan-Kettering Cancer Center	New York	New York	United States	10174
24	University of North Carolina Hospital at Chapel Hill	Chapel Hill	North Carolina	United States	27599-7305
25	Duke University Medical Center	Durham	North Carolina	United States	27705
26	Wake Forest University Health Sciences	Winston-Salem	North Carolina	United States	27157
27	Jewish Hospital BMT Program	Cincinnati	Ohio	United States	45236
28	University Hospitals of Cleveland/Case Western	Cleveland	Ohio	United States	44106-5061
29	Ohio State/Arthur G. James Cancer Hospital	Columbus	Ohio	United States	43210
30	University of Oklahoma Medical Center	Oklahoma City	Oklahoma	United States	73104
31	Oregon Health & Science University	Portland	Oregon	United States	97239-3098
32	Penn State College of Medicine, The Milton S. Hershey Medical Center	Hershey	Pennsylvania	United States	17033
33	University of Pennsylvania Cancer Center	Philadelphia	Pennsylvania	United States	19104
34	Sarah Cannon Blood & Marrow Transplant Program	Nashville	Tennessee	United States	37203
35	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37232-8210
36	University of Texas Southwestern Medical Center	Dallas	Texas	United States	75390
37	University of Texas/MD Anderson CRC	Houston	Texas	United States	77030
38	Texas Transplant Institute	San Antonio	Texas	United States	78229
39	Fred Hutchinson Cancer Research Center	Seattle	Washington	United States	98109-1024
40	West Virginia University Hospital	Morgantown	West Virginia	United States	26506
41	University of Wisconsin Hospital & Clinics	Madison	Wisconsin	United States	53792-5156
42	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)

• Study Protocol - Apr 28, 2016
• Statistical Analysis Plan - May 15, 2019

More Information

Additional Information:

• Blood and Marrow Transplant Clinical Trials Network
• National Marrow Donor Program

Publications

None provided.

• Responsible Party: National Heart, Lung, and Blood Institute (NHLBI)
• ClinicalTrials.gov Identifier: NCT02322320
• Other Study ID Numbers: BMTCTN07LT; U01HL069294-05
• First Posted: Dec 23, 2014
• Last Update Posted: May 11, 2020
• Last Verified: Sep 1, 2019

• 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; Progression; Long-term; Anti-Myeloma Agents; Hematologic Disorders
• Additional relevant MeSH terms: Multiple Myeloma; Lenalidomide

Study Results

Participant Flow

Arm/Group Title	Tandem Auto Transplant	RVD Consolidation	Lenalidomide Maintenance
Arm/Group Description	Initial autologous transplant followed by a second autologous transplant and lenalidomide maintenance Lenalidomide: In BMT CTN 0702, maintenance therapy with lenalidomide started at 10 mg daily for three months and increased to 15 mg daily. The duration of maintenance was three years in all treatment arms. Lenalidomide will be administered initially at the patient's last documented dose prior to discontinuation of BMT CTN 0702 lenalidomide maintenance therapy. Cycle duration is 28 days. Patients will continue lenalidomide until disease progression, or discontinuation due to toxicity, death, or withdrawal from the study.	Initial autologous transplant followed by lenalidomide, bortezomib and dexamethasone (RVD) consolidation and lenalidomide maintenance Lenalidomide: In BMT CTN 0702, maintenance therapy with lenalidomide started at 10 mg daily for three months and increased to 15 mg daily. The duration of maintenance was three years in all treatment arms. Lenalidomide will be administered initially at the patient's last documented dose prior to discontinuation of BMT CTN 0702 lenalidomide maintenance therapy. Cycle duration is 28 days. Patients will continue lenalidomide until disease progression, or discontinuation due to toxicity, death, or withdrawal from the study.	Initial autologous transplant followed by lenalidomide maintenance Lenalidomide: In BMT CTN 0702, maintenance therapy with lenalidomide started at 10 mg daily for three months and increased to 15 mg daily. The duration of maintenance was three years in all treatment arms. Lenalidomide will be administered initially at the patient's last documented dose prior to discontinuation of BMT CTN 0702 lenalidomide maintenance therapy. Cycle duration is 28 days. Patients will continue lenalidomide until disease progression, or discontinuation due to toxicity, death, or withdrawal from the study.
Period Title: Overall Study
STARTED	98	86	89
COMPLETED	98	86	89
NOT COMPLETED	0	0	0

Baseline Characteristics

Arm/Group Title	Tandem Auto Transplant	RVD Consolidation	Lenalidomide Maintenance	Total
Arm/Group Description	Initial autologous transplant followed by a second autologous transplant and lenalidomide maintenance Lenalidomide: In BMT CTN 0702, maintenance therapy with lenalidomide started at 10 mg daily for three months and increased to 15 mg daily. The duration of maintenance was three years in all treatment arms. Lenalidomide will be administered initially at the patient's last documented dose prior to discontinuation of BMT CTN 0702 lenalidomide maintenance therapy. Cycle duration is 28 days. Patients will continue lenalidomide until disease progression, or discontinuation due to toxicity, death, or withdrawal from the study.	Initial autologous transplant followed by lenalidomide, bortezomib and dexamethasone (RVD) consolidation and lenalidomide maintenance Lenalidomide: In BMT CTN 0702, maintenance therapy with lenalidomide started at 10 mg daily for three months and increased to 15 mg daily. The duration of maintenance was three years in all treatment arms. Lenalidomide will be administered initially at the patient's last documented dose prior to discontinuation of BMT CTN 0702 lenalidomide maintenance therapy. Cycle duration is 28 days. Patients will continue lenalidomide until disease progression, or discontinuation due to toxicity, death, or withdrawal from the study.	Initial autologous transplant followed by lenalidomide maintenance Lenalidomide: In BMT CTN 0702, maintenance therapy with lenalidomide started at 10 mg daily for three months and increased to 15 mg daily. The duration of maintenance was three years in all treatment arms. Lenalidomide will be administered initially at the patient's last documented dose prior to discontinuation of BMT CTN 0702 lenalidomide maintenance therapy. Cycle duration is 28 days. Patients will continue lenalidomide until disease progression, or discontinuation due to toxicity, death, or withdrawal from the study.	Total of all reporting groups
Overall Participants	98	86	89	273
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	55	56	57	56
Sex: Female, Male (Count of Participants)
Female	40 40.8%	31 36%	34 38.2%	105 38.5%
Male	58 59.2%	55 64%	55 61.8%	168 61.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	11 11.2%	5 5.8%	2 2.2%	18 6.6%
Not Hispanic or Latino	81 82.7%	77 89.5%	84 94.4%	242 88.6%
Unknown or Not Reported	6 6.1%	4 4.7%	3 3.4%	13 4.8%
Race/Ethnicity, Customized (Count of Participants)
Asian	2 2%	5 5.8%	4 4.5%	11 4%
Black or African American	22 22.4%	10 11.6%	16 18%	48 17.6%
White	68 69.4%	69 80.2%	68 76.4%	205 75.1%
Multiracial	2 2%	0 0%	1 1.1%	3 1.1%
Other	1 1%	0 0%	0 0%	1 0.4%
Unknown or Not Reported	3 3.1%	2 2.3%	0 0%	5 1.8%
Karnofsky Performance Score (KPS) (Count of Participants)
90-100	78 79.6%	60 69.8%	63 70.8%	201 73.6%
70-80	20 20.4%	26 30.2%	26 29.2%	72 26.4%
Diseae Risk at BMT CTN 0702 Enrollment (Count of Participants)
Standard	73 74.5%	65 75.6%	72 80.9%	210 76.9%
High	25 25.5%	21 24.4%	17 19.1%	63 23.1%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Progression-free Survival (PFS)
Description	This analysis includes all randomized subjects from the BMT CTN 0702 protocol classified according to their randomized treatment assignment (intention-to-treat). Progression-free survival is defined as survival without disease progression or initiation of non-protocol anti-myeloma therapy. To account for loss to follow-up, the Kaplan-Meier estimator was used to estimate progression-free survival during the 5 year post-randomization follow-up period.
Time Frame	5 years post-randomization in BMT CTN 0702

Outcome Measure Data

Analysis Population Description

All 754 randomized BMT CTN 0702 participants are included in this analysis

Arm/Group Title	Tandem Auto Transplant	RVD Consolidation	Lenalidomide Maintenance
Arm/Group Description	Initial autologous transplant followed by a second autologous transplant and lenalidomide maintenance Lenalidomide: In BMT CTN 0702, maintenance therapy with lenalidomide started at 10 mg daily for three months and increased to 15 mg daily. The duration of maintenance was three years in all treatment arms. Lenalidomide will be administered initially at the patient's last documented dose prior to discontinuation of BMT CTN 0702 lenalidomide maintenance therapy. Cycle duration is 28 days. Patients will continue lenalidomide until disease progression, or discontinuation due to toxicity, death, or withdrawal from the study.	Initial autologous transplant followed by lenalidomide, bortezomib and dexamethasone (RVD) consolidation and lenalidomide maintenance Lenalidomide: In BMT CTN 0702, maintenance therapy with lenalidomide started at 10 mg daily for three months and increased to 15 mg daily. The duration of maintenance was three years in all treatment arms. Lenalidomide will be administered initially at the patient's last documented dose prior to discontinuation of BMT CTN 0702 lenalidomide maintenance therapy. Cycle duration is 28 days. Patients will continue lenalidomide until disease progression, or discontinuation due to toxicity, death, or withdrawal from the study.	Initial autologous transplant followed by lenalidomide maintenance Lenalidomide: In BMT CTN 0702, maintenance therapy with lenalidomide started at 10 mg daily for three months and increased to 15 mg daily. The duration of maintenance was three years in all treatment arms. Lenalidomide will be administered initially at the patient's last documented dose prior to discontinuation of BMT CTN 0702 lenalidomide maintenance therapy. Cycle duration is 28 days. Patients will continue lenalidomide until disease progression, or discontinuation due to toxicity, death, or withdrawal from the study.
Measure Participants	247	254	257
Number (95% Confidence Interval) [percentage of participants]	47.7 48.7%	44.1 51.3%	45.0 50.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tandem Auto Transplant, RVD Consolidation
	Comments	The null hypothesis is that the percentages of participants with PFS at 5 years post-randomization in BMT CTN 0702 are equal for those assigned to Tandem auto transplant and RVD consolidation therapy.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.60
	Comments	The primary analysis involved pairwise comparisons of PFS between the three treatment arms. To control the familywise type I error rate at 0.05, two-sided testing was performed at a Bonferroni-adjusted significance level of 0.0167 = 0.05 / 3.
	Method	Log Rank
	Comments	The log rank test was stratified on risk status at BMT CTN 0702 enrollment (high risk vs. standard risk)

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Tandem Auto Transplant, Lenalidomide Maintenance
	Comments	The null hypothesis is that the percentages of participants with PFS at 5 years post-randomization in BMT CTN 0702 are equal for those assigned to Tandem auto transplant and Lenalidomide maintenance therapy.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.35
	Comments	The primary analysis involved pairwise comparisons of PFS between the three treatment arms. To control the familywise type I error rate at 0.05, two-sided testing was performed at a Bonferroni-adjusted significance level of 0.0167 = 0.05 / 3.
	Method	Log Rank
	Comments	The log rank test was stratified on risk status at BMT CTN 0702 enrollment (high risk vs. standard risk)

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	RVD Consolidation, Lenalidomide Maintenance
	Comments	The null hypothesis is that the percentages of participants with PFS at 5 years post-randomization in BMT CTN 0702 are equal for those assigned to RVD consolidation and Lenalidomide maintenance therapy.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.68
	Comments	The primary analysis involved pairwise comparisons of PFS between the three treatment arms. To control the familywise type I error rate at 0.05, two-sided testing was performed at a Bonferroni-adjusted significance level of 0.0167 = 0.05 / 3.
	Method	Log Rank
	Comments	The log rank test was stratified on risk status at BMT CTN 0702 enrollment (high risk vs. standard risk)

2. Secondary Outcome

Title	Percentage of Participants With Overall Survival (OS)
Description	This analysis includes all randomized subjects from the BMT CTN 0702 protocol classified according to their randomized treatment assignment (intention-to-treat). Overall survival is defined as survival of death from any cause. To account for loss to follow-up, the Kaplan-Meier estimator was used to estimate overall survival during the 5 year post-randomization follow-up period.
Time Frame	5 years post-randomization in BMT CTN 0702

Outcome Measure Data

Analysis Population Description

All 754 randomized BMT CTN 0702 participants are included in this analysis

Arm/Group Title	Tandem Auto Transplant	RVD Consolidation	Lenalidomide Maintenance
Arm/Group Description	Initial autologous transplant followed by a second autologous transplant and lenalidomide maintenance Lenalidomide: In BMT CTN 0702, maintenance therapy with lenalidomide started at 10 mg daily for three months and increased to 15 mg daily. The duration of maintenance was three years in all treatment arms. Lenalidomide will be administered initially at the patient's last documented dose prior to discontinuation of BMT CTN 0702 lenalidomide maintenance therapy. Cycle duration is 28 days. Patients will continue lenalidomide until disease progression, or discontinuation due to toxicity, death, or withdrawal from the study.	Initial autologous transplant followed by lenalidomide, bortezomib and dexamethasone (RVD) consolidation and lenalidomide maintenance Lenalidomide: In BMT CTN 0702, maintenance therapy with lenalidomide started at 10 mg daily for three months and increased to 15 mg daily. The duration of maintenance was three years in all treatment arms. Lenalidomide will be administered initially at the patient's last documented dose prior to discontinuation of BMT CTN 0702 lenalidomide maintenance therapy. Cycle duration is 28 days. Patients will continue lenalidomide until disease progression, or discontinuation due to toxicity, death, or withdrawal from the study.	Initial autologous transplant followed by lenalidomide maintenance Lenalidomide: In BMT CTN 0702, maintenance therapy with lenalidomide started at 10 mg daily for three months and increased to 15 mg daily. The duration of maintenance was three years in all treatment arms. Lenalidomide will be administered initially at the patient's last documented dose prior to discontinuation of BMT CTN 0702 lenalidomide maintenance therapy. Cycle duration is 28 days. Patients will continue lenalidomide until disease progression, or discontinuation due to toxicity, death, or withdrawal from the study.
Measure Participants	247	254	257
Number (95% Confidence Interval) [percentage of participants]	74.7 76.2%	75.4 87.7%	76.4 85.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tandem Auto Transplant, RVD Consolidation
	Comments	The null hypothesis is that the percentages of participants with OS at 5 years post-randomization in BMT CTN 0702 are equal for those assigned to Tandem auto transplant and RVD consolidation therapy.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.57
	Comments	The analysis involved pairwise comparisons of OS between the three treatment arms. To control the familywise type I error rate at 0.05, two-sided testing was performed at a Bonferroni-adjusted significance level of 0.0167 = 0.05 / 3.
	Method	Log Rank
	Comments	The log rank test was stratified on risk status at BMT CTN 0702 enrollment (high risk vs. standard risk)

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Tandem Auto Transplant, Lenalidomide Maintenance
	Comments	The null hypothesis is that the percentages of participants with OS at 5 years post-randomization in BMT CTN 0702 are equal for those assigned to Tandem auto transplant and Lenalidomide maintenance therapy.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.38
	Comments	The analysis involved pairwise comparisons of OS between the three treatment arms. To control the familywise type I error rate at 0.05, two-sided testing was performed at a Bonferroni-adjusted significance level of 0.0167 = 0.05 / 3.
	Method	Log Rank
	Comments	The log rank test was stratified on risk status at BMT CTN 0702 enrollment (high risk vs. standard risk)

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	RVD Consolidation, Lenalidomide Maintenance
	Comments	The null hypothesis is that the percentages of participants with OS at 5 years post-randomization in BMT CTN 0702 are equal for those assigned to RVD consolidation and Lenalidomide maintenance therapy.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.77
	Comments	The analysis involved pairwise comparisons of OS between the three treatment arms. To control the familywise type I error rate at 0.05, two-sided testing was performed at a Bonferroni-adjusted significance level of 0.0167 = 0.05 / 3.
	Method	Log Rank
	Comments	The log rank test was stratified on risk status at BMT CTN 0702 enrollment (high risk vs. standard risk)

3. Secondary Outcome

Title	Percentage of Participants With Event-free Survival (EFS)
Description	This analysis includes all randomized subjects from the BMT CTN 0702 protocol classified according to their randomized treatment assignment (intention-to-treat). Event-free survival is defined as survival without disease progression, second primary malignancy, and death. To account for loss to follow-up, the Kaplan-Meier estimator was used to estimate event-free survival during the 5 year post-randomization follow-up period.
Time Frame	5 years post-randomization in BMT CTN 0702

Outcome Measure Data

Analysis Population Description

All 754 randomized BMT CTN 0702 participants are included in this analysis

Arm/Group Title	Tandem Auto Transplant	RVD Consolidation	Lenalidomide Maintenance
Arm/Group Description	Initial autologous transplant followed by a second autologous transplant and lenalidomide maintenance Lenalidomide: In BMT CTN 0702, maintenance therapy with lenalidomide started at 10 mg daily for three months and increased to 15 mg daily. The duration of maintenance was three years in all treatment arms. Lenalidomide will be administered initially at the patient's last documented dose prior to discontinuation of BMT CTN 0702 lenalidomide maintenance therapy. Cycle duration is 28 days. Patients will continue lenalidomide until disease progression, or discontinuation due to toxicity, death, or withdrawal from the study.	Initial autologous transplant followed by lenalidomide, bortezomib and dexamethasone (RVD) consolidation and lenalidomide maintenance Lenalidomide: In BMT CTN 0702, maintenance therapy with lenalidomide started at 10 mg daily for three months and increased to 15 mg daily. The duration of maintenance was three years in all treatment arms. Lenalidomide will be administered initially at the patient's last documented dose prior to discontinuation of BMT CTN 0702 lenalidomide maintenance therapy. Cycle duration is 28 days. Patients will continue lenalidomide until disease progression, or discontinuation due to toxicity, death, or withdrawal from the study.	Initial autologous transplant followed by lenalidomide maintenance Lenalidomide: In BMT CTN 0702, maintenance therapy with lenalidomide started at 10 mg daily for three months and increased to 15 mg daily. The duration of maintenance was three years in all treatment arms. Lenalidomide will be administered initially at the patient's last documented dose prior to discontinuation of BMT CTN 0702 lenalidomide maintenance therapy. Cycle duration is 28 days. Patients will continue lenalidomide until disease progression, or discontinuation due to toxicity, death, or withdrawal from the study.
Measure Participants	247	254	257
Number (95% Confidence Interval) [percentage of participants]	44.2 45.1%	42.1 49%	42.4 47.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tandem Auto Transplant, RVD Consolidation
	Comments	The null hypothesis is that the percentages of participants with EFS at 5 years post-randomization in BMT CTN 0702 are equal for those assigned to Tandem auto transplant and RVD consolidation therapy.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.67
	Comments	The analysis involved pairwise comparisons of EFS between the three treatment arms. To control the familywise type I error rate at 0.05, two-sided testing was performed at a Bonferroni-adjusted significance level of 0.0167 = 0.05 / 3.
	Method	Log Rank
	Comments	The log rank test was stratified on risk status at BMT CTN 0702 enrollment (high risk vs. standard risk)

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Tandem Auto Transplant, Lenalidomide Maintenance
	Comments	The null hypothesis is that the percentages of participants with EFS at 5 years post-randomization in BMT CTN 0702 are equal for those assigned to Tandem auto transplant and Lenalidomide maintenance therapy.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.20
	Comments	The analysis involved pairwise comparisons of EFS between the three treatment arms. To control the familywise type I error rate at 0.05, two-sided testing was performed at a Bonferroni-adjusted significance level of 0.0167 = 0.05 / 3.
	Method	Log Rank
	Comments	The log rank test was stratified on risk status at BMT CTN 0702 enrollment (high risk vs. standard risk)

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	RVD Consolidation, Lenalidomide Maintenance
	Comments	The null hypothesis is that the percentages of participants with EFS at 5 years post-randomization in BMT CTN 0702 are equal for those assigned to RVD consolidation and Lenalidomide maintenance therapy.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.40
	Comments	The analysis involved pairwise comparisons of EFS between the three treatment arms. To control the familywise type I error rate at 0.05, two-sided testing was performed at a Bonferroni-adjusted significance level of 0.0167 = 0.05 / 3.
	Method	Log Rank
	Comments	The log rank test was stratified on risk status at BMT CTN 0702 enrollment (high risk vs. standard risk)

4. Secondary Outcome

Title	Percentage of Participants With Secondary Primary Malignancies (SPM)
Description	This analysis includes all randomized subjects from the BMT CTN 0702 protocol classified according to their randomized treatment assignment (intention-to-treat). SPM is defined as development of any second malignancy, excluding non-melanoma skin cancers. To account for loss to follow-up, the Aalen-Johansen estimator was used to estimate the cumulative incidence of SPM during the 5 year post-randomization follow-up period. The development of any SPMs excludes non-melanoma skin cancers. Death without SPMs will be considered a competing risk for this event. The cumulative incidence of SPMs will be compared between treatment arms.
Time Frame	5 years post-randomization in BMT CTN 0702

Outcome Measure Data

Analysis Population Description

All 754 randomized BMT CTN 0702 participants are included in this analysis

Arm/Group Title	Tandem Auto Transplant	RVD Consolidation	Lenalidomide Maintenance
Arm/Group Description	Initial autologous transplant followed by a second autologous transplant and lenalidomide maintenance Lenalidomide: In BMT CTN 0702, maintenance therapy with lenalidomide started at 10 mg daily for three months and increased to 15 mg daily. The duration of maintenance was three years in all treatment arms. Lenalidomide will be administered initially at the patient's last documented dose prior to discontinuation of BMT CTN 0702 lenalidomide maintenance therapy. Cycle duration is 28 days. Patients will continue lenalidomide until disease progression, or discontinuation due to toxicity, death, or withdrawal from the study.	Initial autologous transplant followed by lenalidomide, bortezomib and dexamethasone (RVD) consolidation and lenalidomide maintenance Lenalidomide: In BMT CTN 0702, maintenance therapy with lenalidomide started at 10 mg daily for three months and increased to 15 mg daily. The duration of maintenance was three years in all treatment arms. Lenalidomide will be administered initially at the patient's last documented dose prior to discontinuation of BMT CTN 0702 lenalidomide maintenance therapy. Cycle duration is 28 days. Patients will continue lenalidomide until disease progression, or discontinuation due to toxicity, death, or withdrawal from the study.	Initial autologous transplant followed by lenalidomide maintenance Lenalidomide: In BMT CTN 0702, maintenance therapy with lenalidomide started at 10 mg daily for three months and increased to 15 mg daily. The duration of maintenance was three years in all treatment arms. Lenalidomide will be administered initially at the patient's last documented dose prior to discontinuation of BMT CTN 0702 lenalidomide maintenance therapy. Cycle duration is 28 days. Patients will continue lenalidomide until disease progression, or discontinuation due to toxicity, death, or withdrawal from the study.
Measure Participants	247	254	257
Number (95% Confidence Interval) [percentage of participants]	10.8 11%	7.9 9.2%	7.2 8.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tandem Auto Transplant, RVD Consolidation
	Comments	The null hypothesis is that the percentages of participants with SPM at 5 years post-randomization in BMT CTN 0702 are equal for those assigned to Tandem auto transplant and RVD consolidation therapy.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.43
	Comments	The analysis involved pairwise comparisons of SPM between the three treatment arms. To control the familywise type I error rate at 0.05, two-sided testing was performed at a Bonferroni-adjusted significance level of 0.0167 = 0.05 / 3.
	Method	Gray's test
	Comments	Gray's test was stratified on risk status at BMT CTN 0702 enrollment (high risk vs. standard risk)

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Tandem Auto Transplant, Lenalidomide Maintenance
	Comments	The null hypothesis is that the percentages of participants with SPM at 5 years post-randomization in BMT CTN 0702 are equal for those assigned to Tandem auto transplant and Lenalidomide maintenance therapy.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.70
	Comments	The analysis involved pairwise comparisons of SPM between the three treatment arms. To control the familywise type I error rate at 0.05, two-sided testing was performed at a Bonferroni-adjusted significance level of 0.0167 = 0.05 / 3.
	Method	Gray's test
	Comments	Gray's test was stratified on risk status at BMT CTN 0702 enrollment (high risk vs. standard risk)

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	RVD Consolidation, Lenalidomide Maintenance
	Comments	The null hypothesis is that the percentages of participants with SPM at 5 years post-randomization in BMT CTN 0702 are equal for those assigned to RVD consolidation and Lenalidomide maintenance therapy.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.70
	Comments	The analysis involved pairwise comparisons of SPM between the three treatment arms. To control the familywise type I error rate at 0.05, two-sided testing was performed at a Bonferroni-adjusted significance level of 0.0167 = 0.05 / 3.
	Method	Gray's test
	Comments	Gray's test was stratified on risk status at BMT CTN 0702 enrollment (high risk vs. standard risk)

5. Secondary Outcome

Title	Percentage of Participants With Disease Progression
Description	This analysis includes all randomized subjects from BMT CTN 0702, classified by their treatment assignment (intention-to-treat). Disease progression is defined as progression of multiple myeloma, including one or more of the following: Reappearance of serum monoclonal paraprotein at a level >= 0.5 g/dL 24-hour urine protein electrophoresis of at least 200mg paraprotein/24 hours Abnormal free light chain levels of >10 mg/dl, only in patients without measurable paraprotein in serum and urine At least 10% plasma cells in a bone marrow aspirate or trephine biopsy Definite increase in the size of existing bone lesions or soft tissue plasmacytomas Development of new bone lesions or soft tissue plasmacytomas Development of hypercalcemia (corrected serum Ca >11.5 mg/dL or >2.8 mmol/L) not attributable to other causes To account for loss to follow-up, the Aalen-Johansen estimator was used to estimate the cumulative incidence of progression during the follow-up period.
Time Frame	5 years post-randomization in BMT CTN 0702

Outcome Measure Data

Analysis Population Description

All 754 randomized BMT CTN 0702 participants are included in this analysis

Arm/Group Title	Tandem Auto Transplant	RVD Consolidation	Lenalidomide Maintenance
Arm/Group Description	Initial autologous transplant followed by a second autologous transplant and lenalidomide maintenance Lenalidomide: In BMT CTN 0702, maintenance therapy with lenalidomide started at 10 mg daily for three months and increased to 15 mg daily. The duration of maintenance was three years in all treatment arms. Lenalidomide will be administered initially at the patient's last documented dose prior to discontinuation of BMT CTN 0702 lenalidomide maintenance therapy. Cycle duration is 28 days. Patients will continue lenalidomide until disease progression, or discontinuation due to toxicity, death, or withdrawal from the study.	Initial autologous transplant followed by lenalidomide, bortezomib and dexamethasone (RVD) consolidation and lenalidomide maintenance Lenalidomide: In BMT CTN 0702, maintenance therapy with lenalidomide started at 10 mg daily for three months and increased to 15 mg daily. The duration of maintenance was three years in all treatment arms. Lenalidomide will be administered initially at the patient's last documented dose prior to discontinuation of BMT CTN 0702 lenalidomide maintenance therapy. Cycle duration is 28 days. Patients will continue lenalidomide until disease progression, or discontinuation due to toxicity, death, or withdrawal from the study.	Initial autologous transplant followed by lenalidomide maintenance Lenalidomide: In BMT CTN 0702, maintenance therapy with lenalidomide started at 10 mg daily for three months and increased to 15 mg daily. The duration of maintenance was three years in all treatment arms. Lenalidomide will be administered initially at the patient's last documented dose prior to discontinuation of BMT CTN 0702 lenalidomide maintenance therapy. Cycle duration is 28 days. Patients will continue lenalidomide until disease progression, or discontinuation due to toxicity, death, or withdrawal from the study.
Measure Participants	247	254	257
Number (95% Confidence Interval) [percentage of participants]	48.8 49.8%	54.3 63.1%	54.2 60.9%

Adverse Events

Time Frame	22 months post-enrollment to BMT CTN 07LT
Arm/Group Title	Tandem Auto Transplant		RVD Consolidation		Lenalidomide Maintenance
Arm/Group Description	Initial autologous transplant followed by a second autologous transplant and lenalidomide maintenance Lenalidomide: In BMT CTN 0702, maintenance therapy with lenalidomide started at 10 mg daily for three months and increased to 15 mg daily. The duration of maintenance was three years in all treatment arms. Lenalidomide will be administered initially at the patient's last documented dose prior to discontinuation of BMT CTN 0702 lenalidomide maintenance therapy. Cycle duration is 28 days. Patients will continue lenalidomide until disease progression, or discontinuation due to toxicity, death, or withdrawal from the study.		Initial autologous transplant followed by lenalidomide, bortezomib and dexamethasone (RVD) consolidation and lenalidomide maintenance Lenalidomide: In BMT CTN 0702, maintenance therapy with lenalidomide started at 10 mg daily for three months and increased to 15 mg daily. The duration of maintenance was three years in all treatment arms. Lenalidomide will be administered initially at the patient's last documented dose prior to discontinuation of BMT CTN 0702 lenalidomide maintenance therapy. Cycle duration is 28 days. Patients will continue lenalidomide until disease progression, or discontinuation due to toxicity, death, or withdrawal from the study.		Initial autologous transplant followed by lenalidomide maintenance Lenalidomide: In BMT CTN 0702, maintenance therapy with lenalidomide started at 10 mg daily for three months and increased to 15 mg daily. The duration of maintenance was three years in all treatment arms. Lenalidomide will be administered initially at the patient's last documented dose prior to discontinuation of BMT CTN 0702 lenalidomide maintenance therapy. Cycle duration is 28 days. Patients will continue lenalidomide until disease progression, or discontinuation due to toxicity, death, or withdrawal from the study.
All Cause Mortality
	Tandem Auto Transplant		RVD Consolidation		Lenalidomide Maintenance
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/98 (4.1%)		4/86 (4.7%)		2/89 (2.2%)
Serious Adverse Events
	Tandem Auto Transplant		RVD Consolidation		Lenalidomide Maintenance
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/98 (6.1%)		10/86 (11.6%)		6/89 (6.7%)
Cardiac disorders
Atrial fibrillation	0/98 (0%)	0	0/86 (0%)	0	1/89 (1.1%)	1
Supraventricular tachycardia	1/98 (1%)	1	0/86 (0%)	0	0/89 (0%)	0
Gastrointestinal disorders
Small intestinal obstruction	0/98 (0%)	0	0/86 (0%)	0	1/89 (1.1%)	2
Hepatobiliary disorders
Cholecystitis	0/98 (0%)	0	0/86 (0%)	0	1/89 (1.1%)	1
Injury, poisoning and procedural complications
Cervical vertebral fracture	0/98 (0%)	0	1/86 (1.2%)	1	0/89 (0%)	0
Subdural haematoma	0/98 (0%)	0	1/86 (1.2%)	1	1/89 (1.1%)	1
Investigations
Liver function test increased	0/98 (0%)	0	1/86 (1.2%)	1	0/89 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute lymphocytic leukaemia	0/98 (0%)	0	1/86 (1.2%)	1	0/89 (0%)	0
Acute promyelocytic leukaemia	1/98 (1%)	1	0/86 (0%)	0	0/89 (0%)	0
B precursor type acute leukaemia	0/98 (0%)	0	0/86 (0%)	0	1/89 (1.1%)	1
B-cell type acute leukaemia	0/98 (0%)	0	0/86 (0%)	0	1/89 (1.1%)	1
Breast cancer	0/98 (0%)	0	1/86 (1.2%)	1	0/89 (0%)	0
Colon cancer metastatic	0/98 (0%)	0	1/86 (1.2%)	1	0/89 (0%)	0
Hodgkin's disease	0/98 (0%)	0	1/86 (1.2%)	1	1/89 (1.1%)	1
Invasive lobular breast carcinoma	1/98 (1%)	1	0/86 (0%)	0	0/89 (0%)	0
Malignant melanoma	0/98 (0%)	0	1/86 (1.2%)	1	0/89 (0%)	0
Myelodysplastic syndrome	1/98 (1%)	1	1/86 (1.2%)	1	0/89 (0%)	0
Oesophageal adenocarcinoma	1/98 (1%)	1	0/86 (0%)	0	0/89 (0%)	0
Renal cancer	0/98 (0%)	0	1/86 (1.2%)	1	0/89 (0%)	0
Renal cell carcinoma	0/98 (0%)	0	1/86 (1.2%)	1	0/89 (0%)	0
Nervous system disorders
Dizziness	0/98 (0%)	0	1/86 (1.2%)	1	0/89 (0%)	0
Syncope	0/98 (0%)	0	1/86 (1.2%)	1	0/89 (0%)	0
Respiratory, thoracic and mediastinal disorders
Hypoxia	0/98 (0%)	0	0/86 (0%)	0	1/89 (1.1%)	1
Vascular disorders
Deep vein thrombosis	1/98 (1%)	1	0/86 (0%)	0	0/89 (0%)	0
Hypotension	1/98 (1%)	1	0/86 (0%)	0	0/89 (0%)	0
Other (Not Including Serious) Adverse Events
	Tandem Auto Transplant		RVD Consolidation		Lenalidomide Maintenance
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/98 (0%)		0/86 (0%)		0/89 (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.