Stem Cell Transplantation in Individuals With Multiple Myeloma (BMT CTN 0102)

• Sponsor: National Heart, Lung, and Blood Institute (NHLBI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00075829
• Collaborator: Blood and Marrow Transplant Clinical Trials Network (Other), National Cancer Institute (NCI) (NIH), National Marrow Donor Program (Other)
• Enrollment: 710
• Locations: 36
• Arms: 3
• Duration (Months): 111
• Patients Per Site: 19.7
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The study is designed as a Phase III, multi-center trial of tandem autologous transplants versus the strategy of autologous followed by Human Leukocyte Antigen (HLA)-matched sibling non-myeloablative allogeneic transplant. Study subjects will be biologically assigned to the appropriate arm depending on the availability of an HLA-matched sibling. There is a nested randomized phase III trial of observation versus maintenance therapy following the second autologous transplant for patients on the tandem autologous transplant arm.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma	Procedure: One Autologous Transplant; Procedure: Non-Myeloablative Allogeneic Transplant; Procedure: Second Autologous Transplant; Drug: Thalidomide; Drug: Dexamethasone; Behavioral: Observation	Phase 3

Detailed Description

Multiple myeloma (MM), characterized by malignant plasma cell proliferation, bone destruction, and immunodeficiency, is a disease with a median age at diagnosis of approximately 65 years. It is responsible for about 1 percent of all cancer-related deaths in Western Countries. Conventional treatments with chemotherapy and radiation therapy are non-curative but improve quality of life and duration of survival. Attempts to cure myeloma through high-dose therapy followed by autografting or allografting have largely failed due to a combination of relapsed disease or transplant related mortality (TRM). High-dose therapy with autologous transplantation is safe and has low TRM (less than 5%), but is associated with a continuing and nearly universal risk of disease progression and relapse. Even so, autologous transplantation is superior to continued conventional chemotherapy. Recent data indicate that tandem autologous transplants are superior to a single procedure. Even with this approach, patients remain at risk of relapse and additional approaches are needed.

DESIGN NARRATIVE:

The overall study design is that of biologic assignment, based on the availability of an HLA-matched sibling, to one of two treatment strategies for MM patients. Patients without an HLA-matched sibling will undergo tandem autologous transplants. Patients with an HLA-matched sibling will undergo an autologous transplant followed by a non-myeloablative allogeneic transplant. In addition, the tandem autologous transplant recipients will be randomized to either observation or one year of maintenance therapy to begin following the second autologous transplant. The large number of MM patients without an HLA-matched sibling enables us to evaluate the role of maintenance therapy following tandem autologous transplants.

Study Design

• Study Type: Interventional
• Actual Enrollment: 710 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Trial of Tandem Autologous Stem Cell Transplants +/- Post Second Autologous Transplant Maintenance Therapy vs Single Autologous Stem Cell Transplant Followed by Matched Sibling Non-myeloablative Allogeneic Stem Cell Transplant for Patients With Multiple Myeloma (BMT CTN #0102)
• Study Start Date: Dec 1, 2003
• Actual Primary Completion Date: Jun 1, 2012
• Actual Study Completion Date: Mar 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Auto transplants plus Therapy One autologous transplant along with a second autologous transplant will be preformed followed by one year of Dexamethasone and Thalidomide maintenance therapy.	Procedure: One Autologous Transplant; Melphalan will be administered at a dose of 200 mg/m2. Melphalan will be given in one dose infused on Day -2. Melphalan dose is based on ideal body weight (IBW) for patients who weigh 100-120% of their IBW. All patients will receive an autologous graft with a minimum cell dose of 2.0 x 106 CD34+ cells/kg patient weight. Patients will receive ~5 ug/kg/day of Granulocyte-Colony Stimulating Factor (G-CSF) subcutaneously from Day 5 post-transplant until absolute neutrophil count (ANC) > 500/mm3 for two days.; Procedure: Second Autologous Transplant; Upon recovery from the first autograft, but at least 60 days (preferably between 60-120 days) after the first autograft, patients without an HLA-matched sibling donor will receive a second autograft, also conditioned with melphalan 200 mg/m2.; Drug: Thalidomide; Patients will be initiated on a starting dose of 50 mg/day. The dose will be increased weekly by 50 mg as tolerated to achieve a target dose of 200 mg/day. Patients will be treated for 12 months with thalidomide.; Other Names: Thalomid™ ; Drug: Dexamethasone; Patients will receive dexamethasone at a dose of 40 mg per day during Days 1-4 of each month for 12 months. The first dose of dexamethasone to be given the same day the patient starts thalidomide.; Other Names: Decadron, DexPak
Active Comparator: Auto transplants One autologous transplant along with a second autologous transplant will be preformed followed by one year of observation.	Procedure: One Autologous Transplant; Melphalan will be administered at a dose of 200 mg/m2. Melphalan will be given in one dose infused on Day -2. Melphalan dose is based on ideal body weight (IBW) for patients who weigh 100-120% of their IBW. All patients will receive an autologous graft with a minimum cell dose of 2.0 x 106 CD34+ cells/kg patient weight. Patients will receive ~5 ug/kg/day of Granulocyte-Colony Stimulating Factor (G-CSF) subcutaneously from Day 5 post-transplant until absolute neutrophil count (ANC) > 500/mm3 for two days.; Procedure: Second Autologous Transplant; Upon recovery from the first autograft, but at least 60 days (preferably between 60-120 days) after the first autograft, patients without an HLA-matched sibling donor will receive a second autograft, also conditioned with melphalan 200 mg/m2.; Behavioral: Observation; One year of observation post-transplants.
Active Comparator: Auto and Allo transplants One autologous transplant and one non-myeloablative allogeneic transplant will be preformed and followed by one year of observation.	Procedure: One Autologous Transplant; Melphalan will be administered at a dose of 200 mg/m2. Melphalan will be given in one dose infused on Day -2. Melphalan dose is based on ideal body weight (IBW) for patients who weigh 100-120% of their IBW. All patients will receive an autologous graft with a minimum cell dose of 2.0 x 106 CD34+ cells/kg patient weight. Patients will receive ~5 ug/kg/day of Granulocyte-Colony Stimulating Factor (G-CSF) subcutaneously from Day 5 post-transplant until absolute neutrophil count (ANC) > 500/mm3 for two days.; Procedure: Non-Myeloablative Allogeneic Transplant; Upon recovery and at least Day 60 post-autograft, patients with an available 6/6 HLA matched sibling will receive an allograft after non-myeloablative conditioning. Day 0 patients will receive Total Body Irradiation (TBI) 2.0 Gy from a linear accelerator ≤ 20 cGy/min, followed by allogeneic peripheral blood stem cell (PBSC) infusion. Commence cyclosporine (CSA) on Day -3 at 5 mg/kg bid PO for a daily dose of 10 mg/kg/day through Day +84 based on actual body weight. Starting on Day 84, patients in partial or complete response with the absence of graph versus host disease (GVHD) will have CSA tapered so the patient will be off CSA by Day 180. Oral administration of Mycophenolate Mofetil will be at a daily dose of 30 mg/kg/day from the evening of Day 0 until Day 27 post-transplant.; Behavioral: Observation; One year of observation post-transplants.

Outcome Measures

Primary Outcome Measures

1. Progression-Free Survival (PFS) [Year 3]

   Patients are considered a failure for this endpoint if they die or if they progress or relapse.

Secondary Outcome Measures

1. Overall Survival (OS) for Standard Risk [Years 1, 2, and 3]

   The event is death from any cause, patients alive at the time of last observation are considered censored.

2. Overall Survival (OS) for High Risk [Year 3]

   The event is death from any cause, patients alive at the time of last observation are considered censored.

3. Cumulative Incidence of Progression/Relapse [Year 3]

   Patients are considered experiencing an event when they progress. Deaths without progression are considered as a competing risk. Patients initiating non-protocol anti-myeloma therapy are considered to have progressed on this protocol.

4. Cumulative Incidence of Treatment Related Mortality (TRM) [Year 3]

   TRM is defined as death occurring in a patient from causes other than relapse or progression.

5. Interval From First to Second Transplantation [Year 1]

   Upon recovery from the first autograft, but at least 60 days (preferably between 60-120 days) after the first autograft, patients will receive a second transplant according to treatment assignments.

6. Incidences of Graft Versus Host Disease (GVHD) [Day 100]

   Incidence and severity of GVHD will be scored according to the BMT clinical trials network Manual of Procedures.

7. Incidences of Chronic GVHD [Years 1 and 2]

   Incidence and severity of chronic GVHD will be scored according to the BMT clinical trials network Manual of Procedures.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Meeting the Durie and Salmon criteria for initial diagnosis of MM

• Stage II or III MM at diagnosis or anytime thereafter

• Symptomatic MM requiring treatment at diagnosis or anytime thereafter

• Received at least three cycles of initial systemic therapy and are within 2-10 months of initiation of the initial therapy (this time frame excludes the time for mobilization therapy)

• If receiving chemotherapy-based mobilization regimens, must be able to receive high-dose melphalan between 2 and 8 weeks after the initiation of mobilization therapy whether delivered at the transplant center or at a referring center

• Adequate organ function as measured by:

1. Cardiac: Left ventricular ejection fraction at rest greater than 40%

2. Hepatic: Bilirubin less than 2 times the upper limit of normal and alanine transaminase (ALT) and aspartate transaminase (AST) less than 3 times the upper limit of normal

3. Renal: Creatinine clearance greater than 40 ml/min (measured or calculated/estimated)

4. Pulmonary: Carbon monoxide diffusion (DLCO), Volume forcibly exhaled in one second (FEV1), and Forced Vital Capacity (FVC) greater than 50% of predicted value (corrected for hemoglobin), or O2 saturation greater than 92% of room air

• An adequate autologous graft defined as a cryopreserved PBSC graft containing at least 4.0 x 106 CD34+ cells/kg patient weight; if prior to enrollment it is known that a patient will be on the auto-allo arm (i.e., a consenting, eligible HLA-matched sibling donor is available), the required autograft must contain at least 2.0 x 10^{6 CD34+ cells/kg patient weight; the graft may not be CD34+ selected or otherwise manipulated to remove tumor or other cells; the graft can be collected at the transplanting institution or by a referring center; for patients without an HLA-matched sibling donor, the autograft must be stored so that there are two products each containing at least 2 x 10}6 CD34+ cells/kg patient weight

Exclusion Criteria:

• Never advanced beyond Stage I MM since diagnosis

• 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)

• Plasma cell leukemia

• Karnofsky performance score less than 70%, unless approved by the Medical Monitor or one of the Protocol Chairs

• Uncontrolled hypertension

• Uncontrolled bacterial, viral, or fungal infections (currently taking medication and progression of clinical symptoms)

• Prior malignancies except resected basal cell carcinoma or treated cervical carcinoma in situ; cancer treated with curative intent less than 5 years previously will not be allowed unless approved by the Medical Monitor or one of the Protocol Chairs; cancer treated with curative intent more than 5 years previously will be allowed

• Pregnant or breastfeeding

• Seropositive for the human immunodeficiency virus (HIV)

• Unwilling to use contraceptive techniques during and for 12 months following treatment

• Prior allograft or prior autograft

• Received mid-intensity melphalan (more than 50 mg IV) as part of prior therapy

• Prior organ transplant requiring immunosuppressive therapy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35294
2	City of Hope Samaritan	Phoenix	Arizona	United States	85006
3	City of Hope National Medical Center	Duarte	California	United States	91010-3000
4	Scripps Clinic/Green Hospital	La Jolla	California	United States	92037-1027
5	UCSD Medical Center	La Jolla	California	United States	92093
6	Stanford Hospital and Clinics	Stanford	California	United States	94305
7	Colorado Blood Cancer Institute	Denver	Colorado	United States	80218
8	University of Florida College of Medicine (Shands)	Gainesville	Florida	United States	32610-100277
9	Emory University	Atlanta	Georgia	United States	30322
10	BMT Group of Georgia/Northside Hospital	Atlanta	Georgia	United States	30342
11	Loyola University	Maywood	Illinois	United States	60156
12	IBMT (Indiana Blood and Marrow Transplant) at St Francis Franciscan Health	Indianapolis	Indiana	United States	46237
13	Wichita CCOP	Wichita	Kansas	United States	67214
14	Tufts - New England Medical Center	Boston	Massachusetts	United States	02111
15	DFCI/Brigham & Women's	Boston	Massachusetts	United States	02114
16	University of Michigan Medical Center	Ann Arbor	Michigan	United States	48109-0942
17	University of Minnesota	Minneapolis	Minnesota	United States	55455
18	University of Nebraska Medical Center	Omaha	Nebraska	United States	68198
19	Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
20	Memorial Sloan-Kettering Cancer Center	New York	New York	United States	10021
21	Duke University Medical Center	Durham	North Carolina	United States	27710
22	Jewish Hospital BMT Program	Cincinnati	Ohio	United States	45236
23	University Hospitals of Cleveland/Case Western	Cleveland	Ohio	United States	44106
24	University of Oklahoma Medical Center	Oklahoma City	Oklahoma	United States	73104
25	Oregon Health Sciences University (A)	Portland	Oregon	United States	97239-3098
26	University of Pennsylvania Cancer Center	Philadelphia	Pennsylvania	United States	19104
27	Fox Chase - Temple University - BMT Program	Philadelphia	Pennsylvania	United States	19111-2442
28	Vanderbilt University	Nashville	Tennessee	United States	37232
29	Baylor College of Medicine/The Methodist Hospital	Houston	Texas	United States	77030
30	University of Texas/MD Anderson Cancer Research Center	Houston	Texas	United States	77030
31	Texas Transplant Institute	San Antonio	Texas	United States	78229
32	Utah BMT/Univ of Utah Med School	Salt Lake City	Utah	United States	84132
33	Virginia Commonwealth University MCV Hospitals	Richmond	Virginia	United States	23298
34	Fred Hutchinson Cancer Research Center	Seattle	Washington	United States	98109-1024
35	University of Wisconsin Hospitals & Clinics	Madison	Wisconsin	United States	53792-6164
36	Medical College of Wisconsin	Milwaukee	Wisconsin	United States	53226

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, Statistical Analysis Plan, and Informed Consent Form - May 15, 2006

More Information

Additional Information:

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

Publications

None provided.

• Responsible Party: National Heart, Lung, and Blood Institute (NHLBI)
• ClinicalTrials.gov Identifier: NCT00075829
• Other Study ID Numbers: BMTCTN0102; BMT CTN 0102; SUMC-79730; 417; NCT00321607; NCT00386568
• First Posted: Jan 13, 2004
• Last Update Posted: Nov 1, 2021
• Last Verified: Aug 1, 2017

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by National Heart, Lung, and Blood Institute (NHLBI): Stage II Multiple Myeloma; Stage III Multiple Myeloma; Refractory Plasma Cell Neoplasm
• Additional relevant MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell; Thalidomide; Dexamethasone

Study Results

Participant Flow

Recruitment Details	Participants were enrolled between December 2003 and March 2007 from 37 different transplant centers.

Arm/Group Title	Auto-Auto Standard Risk	Auto-Allo Standard Risk	Auto-Auto High Risk	Auto-Allo High Risk
Arm/Group Description	Tandem autologous transplant plus thalidomide/dexamethasone (Thal-Dex) or observation (Obs) for standard risk patients PFS and OS did not differ between the Thal-Dex and the Obs arms and were thus pooled for analysis.	Autologous transplant plus non-myeloablative allogeneic transplant for standard risk patients	Tandem autologous transplant plus thalidomide/dexamethasone (Thal-Dex) or observation (Obs) for high risk patients PFS and OS did not differ between the Thal-Dex and the Obs arms and were thus pooled for analysis.	Autologous transplant plus non-myeloablative allogeneic transplant for high risk patients
Period Title: Overall Study
STARTED	436	189	48	37
COMPLETED	178	71	14	13
NOT COMPLETED	258	118	34	24

Baseline Characteristics

Arm/Group Title	Auto-Auto Standard Risk	Auto-Allo Standard Risk	Auto-Auto High Risk	Auto-Allo High Risk	Total
Arm/Group Description	Tandem autologous transplant plus thalidomide/dexamethasone (Thal-Dex) or observation (Obs) for standard risk patients PFS and OS did not differ between the Thal-Dex and the Obs arms and were thus pooled for analysis.	Autologous transplant plus non-myeloablative allogeneic transplant for standard risk patients	Tandem autologous transplant plus thalidomide/dexamethasone (Thal-Dex) or observation (Obs) for high risk patients PFS and OS did not differ between the Thal-Dex and the Obs arms and were thus pooled for analysis.	Autologous transplant plus non-myeloablative allogeneic transplant for high risk patients	Total of all reporting groups
Overall Participants	436	189	48	37	710
Age (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	55	53	57	51	53.2
Sex: Female, Male (Count of Participants)
Female	176 40.4%	78 41.3%	21 43.8%	16 43.2%	291 41%
Male	260 59.6%	111 58.7%	27 56.3%	21 56.8%	419 59%
Race/Ethnicity, Customized (participants) [Number]
African American	77 17.7%	18 9.5%	8 16.7%	3 8.1%	106 14.9%
Caucasian	335 76.8%	161 85.2%	38 79.2%	33 89.2%	567 79.9%
Other	24 5.5%	10 5.3%	2 4.2%	1 2.7%	37 5.2%
Karnofsky Performance score (participants) [Number]
100 - 90	344 78.9%	148 78.3%	27 56.3%	26 70.3%	545 76.8%
< 90	92 21.1%	41 21.7%	21 43.8%	11 29.7%	165 23.2%
β-2 Microglobulin (mg/L) [Median (Full Range) ]
Median (Full Range) [mg/L]	2.0	2.0	4.4	3.7	3.025
Durie-Salmon (participants) [Number]
Stages I-II	142 32.6%	59 31.2%	10 20.8%	9 24.3%	220 31%
Stage III	294 67.4%	130 68.8%	38 79.2%	28 75.7%	490 69%
Interval from diagnosis to transplantation (months) [Median (Full Range) ]
Median (Full Range) [months]	7	7	7	7	7
Disease status (participants) [Number]
CR	41 9.4%	24 12.7%	1 2.1%	3 8.1%	69 9.7%
Near CR	65 14.9%	22 11.6%	1 2.1%	2 5.4%	90 12.7%
Very Good PR	79 18.1%	32 16.9%	1 2.1%	7 18.9%	119 16.8%
PR	158 36.2%	76 40.2%	21 43.8%	14 37.8%	269 37.9%
MR	31 7.1%	17 9%	10 20.8%	3 8.1%	61 8.6%
SD	21 4.8%	6 3.2%	6 12.5%	4 10.8%	37 5.2%
Not Evaluable	30 6.9%	12 6.3%	8 16.7%	4 10.8%	54 7.6%
Unknown	11 2.5%	0 0%	0 0%	0 0%	11 1.5%

Outcome Measures

1. Primary Outcome

Title	Progression-Free Survival (PFS)
Description	Patients are considered a failure for this endpoint if they die or if they progress or relapse.
Time Frame	Year 3

Outcome Measure Data

Analysis Population Description

Patients that completed second transplant

Arm/Group Title	Auto-Auto Standard Risk	Auto-Allo Standard Risk	Auto-Auto High Risk	Auto-Allo High Risk
Arm/Group Description	Tandem autologous transplant plus thalidomide/dexamethasone or observation for standard risk patients	Autologous transplant plus non-myeloablative allogeneic transplant for standard risk patients	Tandem autologous transplant plus thalidomide/dexamethasone or observation for high risk patients	Autologous transplant plus non-myeloablative allogeneic transplant for high risk patients
Measure Participants	366	156	31	29
Number (95% Confidence Interval) [percentage of patients]	46	43	33	40

2. Secondary Outcome

Title	Overall Survival (OS) for Standard Risk
Description	The event is death from any cause, patients alive at the time of last observation are considered censored.
Time Frame	Years 1, 2, and 3

Outcome Measure Data

Analysis Population Description

Patients that completed second transplant

Arm/Group Title	Auto-Auto Standard Risk	Auto-Allo Standard Risk
Arm/Group Description	Tandem autologous transplant plus thalidomide/dexamethasone or observation for standard risk patients	Autologous transplant plus non-myeloablative allogeneic transplant for standard risk patients
Measure Participants	366	156
1 year	95	91
2 years	89	85
3 years	80	77

3. Secondary Outcome

Title	Overall Survival (OS) for High Risk
Description	The event is death from any cause, patients alive at the time of last observation are considered censored.
Time Frame	Year 3

Outcome Measure Data

Analysis Population Description

Patients that completed second transplant

Arm/Group Title	Auto-Auto High Risk	Auto-Allo High Risk
Arm/Group Description	Tandem autologous transplant plus thalidomide/dexamethasone or observation for high risk patients	Autologous transplant plus non-myeloablative allogeneic transplant for high risk patients
Measure Participants	31	29
Number (95% Confidence Interval) [percentage of participants]	67 15.4%	59 31.2%

4. Secondary Outcome

Title	Cumulative Incidence of Progression/Relapse
Description	Patients are considered experiencing an event when they progress. Deaths without progression are considered as a competing risk. Patients initiating non-protocol anti-myeloma therapy are considered to have progressed on this protocol.
Time Frame	Year 3

Outcome Measure Data

Analysis Population Description

Patients that completed second transplant

Arm/Group Title	Auto-Auto Standard Risk	Auto-Allo Standard Risk	Auto-Auto High Risk	Auto-Allo High Risk
Arm/Group Description	Tandem autologous transplant plus thalidomide/dexamethasone or observation for standard risk patients	Autologous transplant plus non-myeloablative allogeneic transplant for standard risk patients	Tandem autologous transplant plus thalidomide/dexamethasone or observation for high risk patients	Autologous transplant plus non-myeloablative allogeneic transplant for high risk patients
Measure Participants	366	156	31	29
Number (95% Confidence Interval) [percentage of patients]	50	46	57	38

5. Secondary Outcome

Title	Cumulative Incidence of Treatment Related Mortality (TRM)
Description	TRM is defined as death occurring in a patient from causes other than relapse or progression.
Time Frame	Year 3

Outcome Measure Data

Analysis Population Description

Patients that completed second transplant

Arm/Group Title	Auto-Auto Standard Risk	Auto-Allo Standard Risk	Auto-Auto High Risk	Auto-Allo High Risk
Arm/Group Description	Tandem autologous transplant plus thalidomide/dexamethasone or observation for standard risk patients	Autologous transplant plus non-myeloablative allogeneic transplant for standard risk patients	Tandem autologous transplant plus thalidomide/dexamethasone or observation for high risk patients	Autologous transplant plus non-myeloablative allogeneic transplant for high risk patients
Measure Participants	366	156	31	29
Number (95% Confidence Interval) [percentage of participants]	4 0.9%	11 5.8%	11 22.9%	22 59.5%

6. Secondary Outcome

Title	Interval From First to Second Transplantation
Description	Upon recovery from the first autograft, but at least 60 days (preferably between 60-120 days) after the first autograft, patients will receive a second transplant according to treatment assignments.
Time Frame	Year 1

Outcome Measure Data

Analysis Population Description

Patients that completed second transplant

Arm/Group Title	Auto-Auto Standard Risk	Auto-Allo Standard Risk	Auto-Auto High Risk	Auto-Allo High Risk
Arm/Group Description	Tandem autologous transplant plus thalidomide/dexamethasone or observation for standard risk patients	Autologous transplant plus non-myeloablative allogeneic transplant for standard risk patients	Tandem autologous transplant plus thalidomide/dexamethasone or observation for high risk patients	Autologous transplant plus non-myeloablative allogeneic transplant for high risk patients
Measure Participants	366	156	31	29
Median (Full Range) [days]	98	105	101	111

7. Secondary Outcome

Title	Incidences of Graft Versus Host Disease (GVHD)
Description	Incidence and severity of GVHD will be scored according to the BMT clinical trials network Manual of Procedures.
Time Frame	Day 100

Outcome Measure Data

Analysis Population Description

GVHD was only assessed on the Auto-Allo arm for standard risk patients that completed second transplant

Arm/Group Title	Auto-Allo Standard Risk
Arm/Group Description	Autologous transplant plus non-myeloablative allogeneic transplant for standard risk patients
Measure Participants	156
Grades II-IV	26
Grades III-IV	9

8. Secondary Outcome

Title	Incidences of Chronic GVHD
Description	Incidence and severity of chronic GVHD will be scored according to the BMT clinical trials network Manual of Procedures.
Time Frame	Years 1 and 2

Outcome Measure Data

Analysis Population Description

GVHD was only assessed on the Auto-Allo arm for standard risk patients that completed second transplant

Arm/Group Title	Auto-Allo Standard Risk
Arm/Group Description	Autologous transplant plus non-myeloablative allogeneic transplant for standard risk patients
Measure Participants	156
1 year	47
2 years	54

Adverse Events

Time Frame	3-years post-first transplant
Adverse Event Reporting Description	Serious adverse events are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected adverse events were required to be reported through the adverse event system per protocol.
Arm/Group Title	Auto-Auto Standard Risk		Auto-Allo Standard Risk		Auto-Auto High Risk		Auto-Allo High Risk
Arm/Group Description	Tandem autologous transplant plus thalidomide/dexamethasone or observation for standard risk patients		Autologous transplant plus non-myeloablative allogeneic transplant for standard risk patients		Tandem autologous transplant plus thalidomide/dexamethasone or observation for high risk patients		Autologous transplant plus non-myeloablative allogeneic transplant for high risk patients
All Cause Mortality
	Auto-Auto Standard Risk		Auto-Allo Standard Risk		Auto-Auto High Risk		Auto-Allo High Risk
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Auto-Auto Standard Risk		Auto-Allo Standard Risk		Auto-Auto High Risk		Auto-Allo High Risk
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	15/436 (3.4%)		10/189 (5.3%)		2/48 (4.2%)		5/37 (13.5%)
Blood and lymphatic system disorders
Thrombocytopenic purpura	0/436 (0%)		0/189 (0%)		0/48 (0%)		1/37 (2.7%)
Cardiac disorders
Myocardial infarction	1/436 (0.2%)		0/189 (0%)		0/48 (0%)		0/37 (0%)
Ear and labyrinth disorders
Deafness	1/436 (0.2%)		0/189 (0%)		0/48 (0%)		0/37 (0%)
Eye disorders
Diplopia	0/436 (0%)		1/189 (0.5%)		0/48 (0%)		0/37 (0%)
Gastrointestinal disorders
Diverticulum	0/436 (0%)		1/189 (0.5%)		0/48 (0%)		0/37 (0%)
General disorders
Accidental death	1/436 (0.2%)		0/189 (0%)		0/48 (0%)		0/37 (0%)
Mucosal inflammation	0/436 (0%)		0/189 (0%)		0/48 (0%)		1/37 (2.7%)
Non-cardiac chest pain	0/436 (0%)		1/189 (0.5%)		0/48 (0%)		0/37 (0%)
Hepatobiliary disorders
Cholecystitis	1/436 (0.2%)		0/189 (0%)		0/48 (0%)		0/37 (0%)
Immune system disorders
Anaphylactic reaction	0/436 (0%)		1/189 (0.5%)		0/48 (0%)		0/37 (0%)
Engraftment syndrome	1/436 (0.2%)		0/189 (0%)		0/48 (0%)		0/37 (0%)
Graft versus host disease	1/436 (0.2%)		0/189 (0%)		0/48 (0%)		1/37 (2.7%)
Infections and infestations
Appendicitis	0/436 (0%)		1/189 (0.5%)		0/48 (0%)		0/37 (0%)
Respiratory syncytial virus infection	1/436 (0.2%)		0/189 (0%)		0/48 (0%)		0/37 (0%)
Viral cardiomyopathy	1/436 (0.2%)		0/189 (0%)		0/48 (0%)		0/37 (0%)
Injury, poisoning and procedural complications
Delayed engraftment	0/436 (0%)		1/189 (0.5%)		0/48 (0%)		0/37 (0%)
Investigations
Fever	0/436 (0%)		0/189 (0%)		0/48 (0%)		1/37 (2.7%)
Liver function test abnormal	0/436 (0%)		1/189 (0.5%)		0/48 (0%)		0/37 (0%)
Musculoskeletal and connective tissue disorders
Muscle haemorrhage	0/436 (0%)		0/189 (0%)		1/48 (2.1%)		0/37 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma	1/436 (0.2%)		0/189 (0%)		0/48 (0%)		0/37 (0%)
Lymphoproliferative disorder	1/436 (0.2%)		0/189 (0%)		0/48 (0%)		0/37 (0%)
Metastasis	1/436 (0.2%)		0/189 (0%)		0/48 (0%)		0/37 (0%)
Myelodysplastic syndrome	1/436 (0.2%)		0/189 (0%)		0/48 (0%)		0/37 (0%)
Nervous system disorders
Cerebrovascular accident	0/436 (0%)		0/189 (0%)		0/48 (0%)		1/37 (2.7%)
Convulsion	0/436 (0%)		0/189 (0%)		0/48 (0%)		1/37 (2.7%)
Psychiatric disorders
Completed suicide	1/436 (0.2%)		0/189 (0%)		0/48 (0%)		0/37 (0%)
Renal and urinary disorders
Renal mass	1/436 (0.2%)		0/189 (0%)		0/48 (0%)		0/37 (0%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome	0/436 (0%)		1/189 (0.5%)		1/48 (2.1%)		0/37 (0%)
Organising pneumonia	1/436 (0.2%)		0/189 (0%)		0/48 (0%)		0/37 (0%)
Pneumonitis	0/436 (0%)		1/189 (0.5%)		0/48 (0%)		0/37 (0%)
Pulmonary embolism	1/436 (0.2%)		0/189 (0%)		0/48 (0%)		0/37 (0%)
Respiratory failure	0/436 (0%)		1/189 (0.5%)		0/48 (0%)		0/37 (0%)
Surgical and medical procedures
Cholecystectomy	0/436 (0%)		0/189 (0%)		0/48 (0%)		1/37 (2.7%)
Gallbladder operation	0/436 (0%)		1/189 (0.5%)		0/48 (0%)		0/37 (0%)
Other (Not Including Serious) Adverse Events
	Auto-Auto Standard Risk		Auto-Allo Standard Risk		Auto-Auto High Risk		Auto-Allo High Risk
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/436 (0.2%)		1/189 (0.5%)		0/48 (0%)		0/37 (0%)
Blood and lymphatic system disorders
Thrombocytopenia	1/436 (0.2%)	1	0/189 (0%)	0	0/48 (0%)	0	0/37 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Angiosarcoma	0/436 (0%)	0	1/189 (0.5%)	1	0/48 (0%)	1	0/37 (0%)	1

Limitations/Caveats

[Not Specified]

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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.