Lenalidomide and Dexamethasone With/Without Stem Cell Transplant in Patients With Multiple Myeloma

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Suzanne Lentzsch, MD, Columbia University
ClinicalTrials.gov Identifier:
NCT01731886
First received: November 19, 2012
Last updated: August 7, 2015
Last verified: August 2015
  Purpose

The study is being done to compare the combination of lenalidomide and dexamethasone followed by autologous peripheral blood stem cell transplant (PBSCT) and lenalidomide and dexamethasone without PBSCT in patients with untreated multiple myeloma. This comparison will include how many subjects respond to each study treatment combination, how long their responses last, whether they live longer, and what side effects are caused by each combination.


Condition Intervention Phase
Multiple Myeloma
Procedure: Autologous peripheral blood stem cell transplant
Drug: Lenalidomide
Drug: Dexamethasone
Procedure: Stem Cell Mobilization
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized Clinical Trial of Lenalidomide (CC-5013) and Dexamethasone With and Without Autologous Peripheral Blood Stem Cell Transplant in Patients With Newly Diagnosed Multiple Myeloma

Resource links provided by NLM:


Further study details as provided by Columbia University:

Primary Outcome Measures:
  • Prevalence of complete response rate [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
    The primary objective of this study is to determine the complete response rate of lenalidomide and low-dose dexamethasone versus that of lenalidomide and low-dose dexamethasone followed by autologous peripheral blood stem cell transplant in patients with newly diagnosed multiple myeloma


Secondary Outcome Measures:
  • Prevalence of overall survival [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
    To compare overall survival and time to progression in subjects receiving autologous peripheral blood stem cell transplant after undergoing induction therapy with lenalidomide and dexamethasone versus in those receiving only lenalidomide and dexamethasone, followed by lenalidomide maintenance in both arms.


Estimated Enrollment: 60
Study Start Date: September 2012
Estimated Study Completion Date: February 2017
Estimated Primary Completion Date: February 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm A
Lenalidomide and dexamethasone for four 28-day cycles, and stem cell mobilization, followed by autologous peripheral blood stem cell transplant followed by maintenance.
Procedure: Autologous peripheral blood stem cell transplant
Subjects deemed suitable by the principal investigator will receive melphalan 200 mg/m2 intravenously on days -2 and -1 or only on day -2, and will undergo autologous peripheral blood stem cell transplantation on day 0. Subjects will receive G-CSF subcutaneously daily beginning on day 5 and until blood counts recover.
Drug: Lenalidomide
ARM A Administered orally at a dose 25 mg daily on days 1-21 of each cycle. ARM B Administered orally at a dose 25 mg daily on days 1-21 of each cycle for 8 cycles. After cycle four, subjects will have peripheral stem cell collection. The final four cycles of lenalidomide and dexamethasone will be started within 4 weeks after stem cell collection.
Other Name: CC-5013, Revlimid
Drug: Dexamethasone
Administered orally at a dose of 40 mg daily on days 1, 8, 15, 22 of each cycle.
Other Name: Decadron, Hexadrol, Dexameth, Dexone, DXM
Procedure: Stem Cell Mobilization
Subjects may receive up to the maximum recommended high-dose of cyclophosphamide at 4 gm/m2 intravenously with mesna at a total of 2.4 gm/m2 intravenously or orally divided over 3 doses. Subjects then will receive mobilization using daily filgrastim (G-CSF) at 10 mcg/kg subcutaneously starting 24 hours after cyclophosphamide is completed and until stem cell collection. The use of AMD3100 (Plerixafor) is permitted. Peripheral stem cell collection will be performed at marrow recovery, usually when WBC is >2500 x 109 cells/liter; platelet count is >20 x 103/mm3.
Active Comparator: Arm B
Lenalidomide and dexamethasone for six to eight 28-day cycles, and stem cell mobilization, followed by maintenance.
Drug: Lenalidomide
ARM A Administered orally at a dose 25 mg daily on days 1-21 of each cycle. ARM B Administered orally at a dose 25 mg daily on days 1-21 of each cycle for 8 cycles. After cycle four, subjects will have peripheral stem cell collection. The final four cycles of lenalidomide and dexamethasone will be started within 4 weeks after stem cell collection.
Other Name: CC-5013, Revlimid
Drug: Dexamethasone
Administered orally at a dose of 40 mg daily on days 1, 8, 15, 22 of each cycle.
Other Name: Decadron, Hexadrol, Dexameth, Dexone, DXM
Procedure: Stem Cell Mobilization
Subjects may receive up to the maximum recommended high-dose of cyclophosphamide at 4 gm/m2 intravenously with mesna at a total of 2.4 gm/m2 intravenously or orally divided over 3 doses. Subjects then will receive mobilization using daily filgrastim (G-CSF) at 10 mcg/kg subcutaneously starting 24 hours after cyclophosphamide is completed and until stem cell collection. The use of AMD3100 (Plerixafor) is permitted. Peripheral stem cell collection will be performed at marrow recovery, usually when WBC is >2500 x 109 cells/liter; platelet count is >20 x 103/mm3.

Detailed Description:

The trial will compare complete response rates and duration of complete response of patients receiving at least 6 to 8 cycles of therapy with lenalidomide plus low-dose dexamethasone and reached plateau of best response (Arm B) versus patients receiving 4 cycles of therapy with lenalidomide plus low-dose dexamethasone followed by autologous peripheral blood stem cell transplant conditioned with 200 mg/m2 melphalan (Arm A). Provide a brief abstract summarizing the specific aims, experimental design, methods and subject population.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically or cytologically confirmed Multiple Myeloma, Salmon-Durie Stage II or III or International Staging System II or III that has not been previously treated.
  • Bone marrow plasmacytosis with > or = 10% plasma cells, or sheets of plasma cells or a biopsy-proven plasmacytoma.
  • Measurable levels of monoclonal protein (M protein): 1 g/dL IgG or .5 g/dL IgA on serum protein electrophoresis or > 200 mg of monoclonal light chain on a 24 hour urine protein electrophoresis.
  • Age > or = 18 years.
  • Life expectancy of greater than 12 months.
  • ECOG performance status < or = 2 (Karnofsky > or = 60%).
  • Adequate organ and marrow function as defined below:

    • Hgb > or = 9 g/dL
    • Absolute Neutrophil Count > or = 1,500/ ml
    • Platelets > or = 50,000/mm3
    • Total Bilirubin < or = 1.5 mg/dL
    • AST(SGOT) / ALT(SGPT) < or = 2.5 X ULN
    • Creatinine < 2.0 mg/dL
    • Creatinine Clearance > or = 50 ml/min
  • Registered into the mandatory Revlimid REMS® program, and be willing and able to comply with the requirements of the REMS® program.
  • Females of reproductive potential must adhere to the scheduled pregnancy testing as required in the Revlimid REMS® program.
  • Ability to understand and the willingness to sign a written informed consent document.
  • Subjects with a history of prior malignancy are eligible provided there is no active malignancy and a low expectation of recurrence within 6 months.
  • Must be willing and able to take prophylaxis with either aspirin at 81 mg/day or alternative prophylaxis with either low molecular weight heparin or warfarin as recommended.
  • Eligible for transplant with an age up to and including 75 years.
  • Subjects in ARM A who are refusing transplant can go onto ARM B and will be evaluated separately.
  • Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 10 - 14 days prior to and again within 24 hours of prescribing lenalidomide and must either commit to continued abstinence or TWO acceptable methods of birth control. FCBP must also agree to ongoing pregnancy testing. Males must agree to use a latex condom.

Exclusion Criteria:

  • Have had chemotherapy or radiotherapy for multiple myeloma within 4 weeks of baseline.
  • Receiving any other investigational agents or therapy within 28 days of baseline.
  • Brain metastases.
  • Subjects who are pregnant or breast feeding.
  • History of previous deep vein thrombosis or pulmonary embolism must be on anticoagulation therapy with low molecular weight heparin or warfarin at therapeutic dosages (e.g. INR 2-3).
  • If a subject is on full-dose anticoagulants, the following criteria should be met for enrollment:

    • Must not have active bleeding or pathological conditions that carry high risk of bleeding (e.g. tumor involving major vessels, known varices).
    • Must not have thrombocytopenia requiring transfusion.
    • Must have a platelet count > 50,000.
    • Must have stable INR between 2-3.
  • Smoldering myeloma or monoclonal gammopathy of undetermined significance.
  • Active, uncontrolled infection.
  • Active, uncontrolled seizure disorder (seizures in the last 6 months).
  • Concurrent use of other anti-cancer agents or treatments.
  • Positive for HIV or infectious hepatitis, type B or C.
  • Hypersensitivity to thalidomide.
  • Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk.
  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: NCT01731886

Locations
United States, New York
Columbia University
New York, New York, United States, 10032
Sponsors and Collaborators
Columbia University
Investigators
Principal Investigator: Suzanne Lentzsch, MD Columbia University
  More Information

No publications provided

Responsible Party: Suzanne Lentzsch, MD, Associate Clinical Professor of Clinical Medicine, Columbia University
ClinicalTrials.gov Identifier: NCT01731886     History of Changes
Other Study ID Numbers: AAAJ2355
Study First Received: November 19, 2012
Last Updated: August 7, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Columbia University:
Stem cell transplant, plasma cell myeloma, multiple myeloma

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Blood Protein Disorders
Cardiovascular Diseases
Hematologic Diseases
Hemorrhagic Disorders
Hemostatic Disorders
Immune System Diseases
Immunoproliferative Disorders
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Paraproteinemias
Vascular Diseases
BB 1101
Dexamethasone
Dexamethasone 21-phosphate
Dexamethasone acetate
Lenalidomide
Thalidomide
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Anti-Bacterial Agents
Anti-Infective Agents
Anti-Inflammatory Agents
Antiemetics
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Autonomic Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on August 27, 2015