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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Blood and Marrow Transplant Clinical Trials Network
Information provided by (Responsible Party):
National Heart, Lung, and Blood Institute (NHLBI)
ClinicalTrials.gov Identifier:
NCT01109004
First received: April 21, 2010
Last updated: December 6, 2013
Last verified: December 2013
  Purpose

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.


Condition Intervention Phase
Multiple Myeloma
Drug: Lenalidomide
Drug: lenalidomide, bortezomib and dexamethasone
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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)

Resource links provided by NLM:


Further study details as provided by National Heart, Lung, and Blood Institute (NHLBI):

Primary Outcome Measures:
  • Three-year progression-free survival (PFS) [ Time Frame: Measured at 3 years ] [ Designated as safety issue: Yes ]
    The primary objective of the randomized trial is to compare PFS between the two single transplant arms and between each single transplant arm and the tandem transplant arm.


Secondary Outcome Measures:
  • Current myeloma-stable survival [ Time Frame: Measured at 4 years post-randomization ] [ Designated as safety issue: Yes ]
  • Three-year overall survival [ Time Frame: Measured at 4 years post-randomization ] [ Designated as safety issue: Yes ]
  • Incidence of progression [ Time Frame: Measured at 4 years post-randomization ] [ Designated as safety issue: Yes ]
  • Incidence of toxicities [ Time Frame: Measured at 4 years post-randomization ] [ Designated as safety issue: Yes ]
  • Incidence of infections [ Time Frame: Measured at 4 years post-randomization ] [ Designated as safety issue: Yes ]
  • Treatment related mortality [ Time Frame: Measured at 4 years post-randomization ] [ Designated as safety issue: Yes ]
  • Non-compliance with medication [ Time Frame: Measured at 4 years post-randomization ] [ Designated as safety issue: Yes ]
  • Quality of life [ Time Frame: Measured at 4 years post-randomization ] [ Designated as safety issue: No ]

Estimated Enrollment: 750
Study Start Date: May 2010
Estimated Study Completion Date: May 2020
Estimated Primary Completion Date: May 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Tandem auto transplant
Initial autologous transplant followed by a second autologous transplant and lenalidomide maintenance
Drug: 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.
Active Comparator: RVD consolidation
Initial autologous transplant followed by lenalidomide, bortezomib and dexamethasone (RVD) consolidation and lenalidomide maintenance
Drug: 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.
Active Comparator: Lenalidomide maintenance
Initial autologous transplant followed by lenalidomide maintenance
Drug: 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.

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   up to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients meeting the criteria for symptomatic multiple myeloma (MM).
  • Patients who are 70 years of age, or younger, at time of enrollment.
  • Patients who have received at least two cycles of any regimen as initial systemic therapy and are within 2 - 12 months of the first dose of initial therapy.
  • Cardiac function: left ventricular ejection fraction at rest greater than 40 percent.
  • Hepatic: bilirubin less than 1.5x the upper limit of normal and ALT and AST less than 2.5x the upper limit of normal. (Patients who have been diagnosed with Gilbert's Disease are allowed to exceed the defined bilirubin value of 1.5x the upper limit of normal.)
  • Renal: Creatinine clearance of grater than or equal to 40 mL/min, estimated or calculated.
  • Pulmonary: DLCO, FEV1, FVC grater than 50 percent of predicted value (corrected for hemoglobin).
  • Patients with an adequate autologous graft defined as a cryopreserved PBSC graft containing greater than or equal to 4 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. The autograft must be stored so that there are two products each containing at least 2 x 10^6 CD34+ cells/kg patient weight.
  • Signed informed consent form.

Exclusion Criteria:

  • Patients who never fulfill the criteria for symptomatic MM.
  • Patients with purely non-secretory MM [absence of a monoclonal protein (M protein) in serum as measured by electrophoresis and immunofixation and the absence of Bence Jones protein in the urine defined by use of conventional electrophoresis and immunofixation techniques]. Patients with light chain MM detected in the serum by free light chain assay are eligible.
  • Patients with plasma cell leukemia.
  • Karnofsky performance score less than 70 percent.
  • Patients with greater than grade 2 sensory neuropathy (CTCAE).
  • Patients with uncontrolled bacterial, viral or fungal infections (currently taking medication and progression of clinical symptoms).
  • Patients seropositive for the human immunodeficiency virus (HIV).
  • Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at Screening has to be documented by the investigator as not medically relevant.
  • Patient has hypersensitivity to bortezomib, boron or mannitol.
  • Patient has received other investigational drugs with 14 days before enrollment.
  • Patients with 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 Protocol Officer or one of the Protocol Chairs. Cancer treated with curative intent greater than 5 years previously is allowed.
  • Female patients who are pregnant (positive B-HCG) or breastfeeding.
  • 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.
  • Prior allograft or prior autograft.
  • Patients who have received mid-intensity melphalan (greater than 50 mg IV) as part of prior therapy.
  • Patients unable or unwilling to provide informed consent.
  • Prior organ transplant requiring immunosuppressive therapy.
  • Patients with disease progression prior to enrollment.
  • Patients who have received lenalidomide as initial therapy for MM and have experienced toxicities resulting in treatment discontinuation.
  • Patients who experienced thromboembolic events while on full anticoagulation during prior therapy with lenalidomide or thalidomide.
  • Patients unwilling to take DVT prophylaxis.
  • Patients who cannot undergo an intervention in any treatment arm due to a priori denial of medical costs coverage by third party payers.
  • Patients unable to unwilling to return to the transplant center for their assigned treatments.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01109004

  Show 55 Study Locations
Sponsors and Collaborators
Blood and Marrow Transplant Clinical Trials Network
Investigators
Study Chair: Amrita Krishnan, MD City of Hope National Medical Center
Study Chair: George Somlo, MD City of Hope National Medical Center
Study Chair: Edward Stadtmauer, MD University of Pennsylvania
  More Information

Additional Information:
No publications provided

Responsible Party: National Heart, Lung, and Blood Institute (NHLBI)
ClinicalTrials.gov Identifier: NCT01109004     History of Changes
Other Study ID Numbers: 690
Study First Received: April 21, 2010
Last Updated: December 6, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by National Heart, Lung, and Blood Institute (NHLBI):
Symptomatic multiple myeloma

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone acetate
Dexamethasone
Dexamethasone 21-phosphate
Bortezomib
Lenalidomide
Thalidomide
BB 1101
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents
Gastrointestinal Agents

ClinicalTrials.gov processed this record on August 27, 2014