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Multiple Myeloma

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Dexamethasone

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Initial autologous transplant followed by a second autologous transplant and lenalidomide maintenance

Initial autologous transplant followed by lenalidomide, bortezomib and dexamethasone (RVD) consolidation and lenalidomide maintenance

Initial autologous transplant followed by lenalidomide maintenance

All patients will undergo a first autologous peripheral blood stem cell (PBSC) transplant with high-dose melphalan (200 mg/m\^2 IV) given on Day -2. Upon recovery from the first transplant patients will receive a second autologous PBSC transplant with the same conditioning regimen as the first transplant. All patients will also receive maintenance lenalidomide which will start after the second transplant. Maintenance therapy with lenalidomide will start at 10 mg daily for 3 months and increase to 15 mg daily. The duration of maintenance will be three years in all treatment arms.

All patients will undergo a first autologous peripheral blood stem cell (PBSC) transplant with high-dose melphalan (200 mg/m\^2 IV) given on Day -2. Upon recovery from the first transplant patients will receive consolidation therapy with RVD (lenalidomide 15 mg/day on Days 1-14, dexamethasone 40mg on Days 1, 8 and 15, and bortezomib 1.3mg/m2 on Days 1, 4, 8 and 11 of every 21 day cycle, patients will receive four cycles). All patients will also receive maintenance lenalidomide which will start after consolidation therapy. Maintenance therapy with lenalidomide will start at 10 mg daily for 3 months and increase to 15 mg daily. The duration of maintenance will be three years in all treatment arms.

lenalidomide, bortezomib and dexamethasone

All patients will undergo a first autologous peripheral blood stem cell (PBSC) transplant with high-dose melphalan (200 mg/m\^2 IV) given on Day -2. Upon recovery from the first transplant patients will receive maintenance with lenalidomide (15 mg daily). Maintenance lenalidomide will start after the first autologous transplant. Maintenance therapy with lenalidomide will start at 10 mg daily for 3 months and increase to 15 mg daily. The duration of maintenance will be three years in all treatment arms.

Mary Horowitz, MD

The study is designed as a Phase III, multicenter trial of tandem autologous transplants plus maintenance therapy versus the strategy of single autologous transplant plus consolidation therapy with lenalidomide, bortezomib and dexamethasone (RVD) followed by maintenance therapy or single autologous transplant plus maintenance therapy as part of upfront treatment of multiple myeloma (MM). Lenalidomide will be used as maintenance therapy for three years in all arms.

The primary objective of the randomized trial is to compare three-year progression-free survival (PFS) between the three treatment arms as a pairwise comparison. Mobilization therapy will not be specified for the study. Randomization to three treatment arms will be done prior to the first transplants. All patients will undergo a first autologous peripheral blood stem cell (PBSC) transplant with high-dose melphalan (200 mg/m\^2 IV) given on Day -2. Upon recovery from the first transplant patients will receive either a second autologous PBSC transplant with the same conditioning regimen as the first transplant or consolidation therapy with RVD (lenalidomide 15 mg/day on Days 1-14, dexamethasone 40 mg on Days 1, 8 and 15, and bortezomib 1.3mg/m\^2 on Days 1, 4, 8 and 11 of every 21 day cycle, patients will receive four cycles) or maintenance with lenalidomide (15 mg daily). All patients will also receive maintenance lenalidomide which will start after the second transplant, after the first autologous transplant or after consolidation therapy depending on the treatment arm. Maintenance therapy with lenalidomide will start at 10 mg daily for three months and increase to 15 mg daily. The duration of maintenance will be three years in all treatment arms.

Stem Cell Transplant With Lenalidomide Maintenance in Patients With Multiple Myeloma (BMT CTN 0702)

A Trial of Single Autologous Transplant With or Without Consolidation Therapy Versus Tandem Autologous Transplant With Lenalidomide Maintenance for Patients With Multiple Myeloma (BMT CTN 0702)

Results will be published in a manuscript and supporting information submitted to NIH BioLINCC (including data dictionaries, case report forms, data submission documentation, documentation for outcomes dataset, etc where indicated).

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 of a few participants, the Kaplan-Meier estimator was used to estimate progression-free survival at 38 months post-randomization.

Disease Progression is defined as progression of multiple myeloma, including one or more of the following:

* A reappearance of serum monoclonal paraprotein, with a level of at least 0.5 g/dL
* 24-hour urine protein electrophoresis with at least 200 mg paraprotein/24 hours
* Abnormal free light chain levels of \>10 mg/dl, only in patients without measurable paraprotein in the serum and urine
* At least 10% plasma cells in a bone marrow aspirate or on 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 any other cause

To account for loss to follow-up of a few participants, the cumulative incidence of TRM at 38 months post-randomization was estimated using the Aalen-Johansen estimator, treating death prior to disease progression as a competing risk.

Overall survival is defined as survival of death from any cause. To account for loss to follow-up of a few participants, the Kaplan-Meier estimator was used to estimate overall survival at 38 months post-randomization.

TRM is defined as death prior to progression of multiple myeloma. To account for loss to follow-up of a few participants, the cumulative incidence of TRM at 38 months post-randomization was estimated using the Aalen-Johansen estimator, treating disease progression as a competing risk.

The number of participants with very good partial response (VGPR) or better \[complete response (CR), near CR (nCR), and stringent CR (sCR)\] according to the International Uniform Response Criteria will be calculated. The "Worse than VGPR" group includes PR, stable disease, and progressive disease.

sCR requires, in addition to CR: Normal free light chain ratio (FLC), Absence of clonal cells in bone marrow CR requires, in addition to nCR: Absence of the original monoclonal paraprotein (PPN), Disappearance of soft tissue plasmacytomas nCR is defined as: \< 5% plasma cells in a bone marrow aspirate, No increase in lytic bone lesions VGPR requires: Serum or urine PPN not detectable on electrophoresis OR \>=90% reduction in serum PPN plus urine PPN \<100 mg/24hrs, \>= 50% reduction in the level of serum monoclonal PPN or reduction in 24 hour urinary monoclonal PPN either \>= 90% or to \<200 mg/24 hours in light chain disease, \>= 50% reduction in the size of soft tissue plasmacytomas

The Functional Assessment of Cancer Therapy-General (FACT-G) is a quality of life instrument that assesses the effects of cancer therapy on a patient's physical, social/family, emotional, and functional well-being. The assessment has 27 questions, each scored on a Likert scale from 0-4. The overall score is computed by adding scores of the questions and falls in the range 0-108, with higher scores indicating higher levels of overall well-being.

The Functional Assessment of Cancer Therapy-Bone Marrow Transplant scale (FACT-BMT) is a quality of life instrument that assesses the effects of bone marrow transplantation (BMT) on a patient's physical, social/family, emotional, and functional well-being while taking into consideration BMT-specific concerns. The assessment has 37 questions, each scored on a Likert scale from 0-4. The overall score is computed by adding scores of the questions and falls in the range 0-148, with higher scores indicating higher levels of overall well-being.

The Functional Assessment of Cancer Therapy (FACT) Trial Outcome Index is a quality of life instrument that assesses the impact of bone marrow transplantation (BMT) on a patient's physical and functional well-being while taking into consideration BMT-specific concerns. The assessment has 24 questions, each scored on a Likert scale from 0-4. The overall score is computed by adding scores of the questions and falls in the range 0-96, with higher scores indicating higher levels of overall well-being.

The Medical Outcome Study (MOS) SF-36 Physical Component Summary is a subscale of the SF-36 intended to measure physical well-being. It is scored on a scale of 0-100, with higher scores indicating higher levels of well-being.

The Medical Outcome Study (MOS) SF-36 Mental Component Summary is a subscale of the SF-36 intended to measure mental well-being. It is scored on a scale of 0-100, with higher scores indicating higher levels of well-being.

Blood and Marrow Transplant Clinical Trials Network

National Cancer Institute (NCI)

National Heart, Lung, and Blood Institute (NHLBI)

Initial autologous transplant followed by a second autologous transplant and lenalidomide maintenance

Lenalidomide: All patients will undergo a first autologous peripheral blood stem cell (PBSC) transplant with high-dose melphalan (200 mg/m\^2 IV) given on Day -2. Upon recovery from the first transplant patients will receive a second autologous PBSC transplant with the same conditioning regimen as the first transplant. All patients will also receive maintenance lenalidomide which will start after the second transplant. Maintenance therapy with lenalidomide will start at 10 mg daily for 3 months and increase to 15 mg daily. The duration of maintenance will be three years in all treatment arms.

Tandem Auto Transplant

Initial autologous transplant followed by lenalidomide, bortezomib and dexamethasone (RVD) consolidation and lenalidomide maintenance

lenalidomide, bortezomib and dexamethasone: All patients will undergo a first autologous peripheral blood stem cell (PBSC) transplant with high-dose melphalan (200 mg/m\^2 IV) given on Day -2. Upon recovery from the first transplant patients will receive consolidation therapy with RVD (lenalidomide 15 mg/day on Days 1-14, dexamethasone 40mg on Days 1, 8 and 15, and bortezomib 1.3mg/m2 on Days 1, 4, 8 and 11 of every 21 day cycle, patients will receive four cycles). All patients will also receive maintenance lenalidomide which will start after consolidation therapy. Maintenance therapy with lenalidomide will start at 10 mg daily for 3 months and increase to 15 mg daily. The duration of maintenance will be three years in all treatment arms.

RVD Consolidation

Initial autologous transplant followed by lenalidomide maintenance

Lenalidomide: All patients will undergo a first autologous peripheral blood stem cell (PBSC) transplant with high-dose melphalan (200 mg/m\^2 IV) given on Day -2. Upon recovery from the first transplant patients will receive maintenance with lenalidomide (15 mg daily). Maintenance lenalidomide will start after the first autologous transplant. Maintenance therapy with lenalidomide will start at 10 mg daily for 3 months and increase to 15 mg daily. The duration of maintenance will be three years in all treatment arms.

Lenalidomide Maintenance

Total

Age, Continuous

Sex: Female, Male

Race/Ethnicity, Customized

KPS describes patient-perceived global quality of life and functioning on a scale of 0-100.

100: No evidence of disease; 90: Normal activity. Minor signs or symptoms of disease; 80: Normal activity with effort. Some signs or symptoms of disease; 70: Cares for self. Unable to continue normal activity; 60: Needs occasional assistance, but cares for most personal needs; 50: Needs considerable assistance and medical care; 40: Disabled. Needs special care and assistance; 30: Severely disabled. Hospital admission indicated; 20: Very sick. Active supportive therapy needed; 10: Moribund; 0: Dead

Karnofsky Performance Score (KPS)

Participants on this study will be stratified for the purposes of statistical analysis into high-risk and standard risk-groups. High-risk multiple myeloma is defined by the presence of high beta-2 microglobulin (\> 5.5mg/L) or the presence of cytogenetic abnormalities including t(4;14), t(14;20), t(14;16), deletion (17p) detected by FISH or standard cytogenetics, deletion 13 detected by standard cytogenetics only or aneuploidy. Participants without cytogenetic analysis available and beta-2 microglobulin ≤ 5.5mg/L or with deletion 13 detected by FISH will be classified as standard-risk disease.

Disease Risk

Initial therapy administered for the treatment of multiple myeloma

Initial Therapy

Time from Initial Therapy to Enrollment

Lines of therapy is defined as the number of different regimens received prior to study entry.

Number of Lines of Therapy

Disease Status at Enrollment

Adam Mendizabal, PhD

The null hypothesis is that the percentages of participants with PFS at 38 months post-randomization are equal for those receiving Tandem auto transplant and RVD consolidation therapy.

The null hypothesis is that the percentages of participants with PFS at 38 months post-randomization are equal for those receiving Tandem auto transplant and Lenalidomide maintenance therapy.

The null hypothesis is that the percentages of participants with PFS at 38 months post-randomization are equal for those receiving RVD consolidation and Lenalidomide maintenance therapy.

Percentage of Participants With Progression-free Survival (PFS)

The null hypothesis is that the percentages of participants with disease progression at 38 months post-randomization are equal for those receiving Tandem auto transplant and RVD consolidation therapy.

The null hypothesis is that the percentages of participants with disease progression at 38 months post-randomization are equal for those receiving Tandem auto transplant and Lenalidomide maintenance therapy.

The null hypothesis is that the percentages of participants with disease progression at 38 months post-randomization are equal for those receiving RVD consolidation and Lenalidomide maintenance therapy.

Percentage of Participants With Disease Progression

The null hypothesis is that the percentages of participants with OS at 38 months post-randomization are equal for those receiving Tandem auto transplant and RVD consolidation therapy.

The null hypothesis is that the percentages of participants with OS at 38 months post-randomization are equal for those receiving Tandem auto transplant and Lenalidomide maintenance therapy.

The null hypothesis is that the percentages of participants with OS at 38 months post-randomization are equal for those receiving RVD consolidation and Lenalidomide maintenance therapy.

Percentage of Participants With Overall Survival (OS)

The null hypothesis is that the percentages of participants with TRM at 38 months post-randomization are equal for those receiving Tandem auto transplant and RVD consolidation therapy.

The null hypothesis is that the percentages of participants with TRM at 38 months post-randomization are equal for those receiving Tandem auto transplant and Lenalidomide maintenance therapy.

The null hypothesis is that the percentages of participants with TRM at 38 months post-randomization are equal for those receiving RVD consolidation and Lenalidomide maintenance therapy.

Percentage of Participants With Treatment-related Mortality (TRM)

1 Year

2 Years

Only participants that were evaluable for disease response were analyzed at each time point. Those who had died or experienced disease progression were excluded.

Number of Participants With Treatment Response

Baseline

3 Years

Outcomes are analyzed from participants that were alive, progression-free, and completed assessments.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Stem Cell Transplant With Lenalidomide Maintenance in Patients With Multiple Myeloma (BMT CTN 0702)	NCT01109004	Multiple Myelom...	Lenalidomide lenalidomide, b... Lenalidomide	- 70 Years	National Heart, Lung, and Blood Institute (NHLBI)
Stem Cell Transplant With Lenalidomide Maintenance in Patients With Multiple Myeloma (BMT CTN 0702)	NCT01109004	Multiple Myelom...	Lenalidomide lenalidomide, b... Lenalidomide	- 70 Years	National Heart, Lung, and Blood Institute (NHLBI)
Stem Cell Transplant With Lenalidomide Maintenance in Patients With Multiple Myeloma (BMT CTN 0702)	NCT01109004	Multiple Myelom...	Lenalidomide lenalidomide, b... Lenalidomide	- 70 Years	National Heart, Lung, and Blood Institute (NHLBI)

Spots Global Cancer Trial Database for rvd consolidation