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

NCT ID: NCT01731886

Last Updated: 2020-02-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-09-30
• Study Completion Date: 2017-04-11

Brief Summary

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 the subjects respond to each study treatment combination, and what side effects are caused by each combination.

Detailed Description

Multiple myeloma is a malignant plasma cell proliferative disorder responsible for 11, 000 deaths each year in the United States. Approximately one third of myeloma patients develop hypercalcemia and about two thirds present with anemia. As the second most common hematologic malignancy, myeloma remains incurable. In the last forty years, options for therapy have included melphalan-prednisone, anthracyclines, and vinca alkaloids; however, relapse with those regimens continues to be inevitable with a median survival of 3 years.

Conditions

Multiple Myeloma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm A

Subjects will receive the current standard of care treatment. Lenalidomide and dexamethasone for four 28-day cycles followed by steam cell collection and autologous peripheral blood stem cell transplant. After 90 days, start the maintenance phase (lenalidomide days 1-21 every 28 days for two years or until your disease progresses).

Group Type: ACTIVE_COMPARATOR

Autologous peripheral blood stem cell transplant

Intervention Type: PROCEDURE

Subjects deemed suitable by the principal investigator will undergo autologous peripheral blood stem cell transplantation on day 0.

Lenalidomide

Intervention Type: DRUG

Administered orally at a dose 25 mg daily on days 1-21 of each 28-day cycle.

Dexamethasone

Intervention Type: DRUG

Administered orally at a dose of 40 mg daily on days 1, 8, 15, 22 of each cycle.

Stem cell collection

Intervention Type: PROCEDURE

Peripheral stem cell collection will be performed at marrow recovery, usually when white blood cell (WBC) is \>2500 x 109 cells/liter; platelet count is \>20 x 103/mm3.

Melphalan

Intervention Type: DRUG

Subjects undergoing autologous peripheral blood stem cell transplant will receive melphalan 200 mg/m2 intravenously on days -2 and -1 or only on day -2.

G-CSF

Intervention Type: DRUG

Subjects will receive G-CSF subcutaneously daily beginning on day 5 and until blood counts recover.

Cyclophosphamide

Intervention Type: DRUG

Subjects may receive up to the maximum recommended high-dose of cyclophosphamide at 4 gm/m2 intravenously.

Mesna

Intervention Type: DRUG

Mesna will be provided with the cyclophosphamide.

Arm B

Subjects will receive the new treatment that will be compared with the standard of care. Lenalidomide and dexamethasone for eight 28-day cycles. After four cycles your stem cells will be collected (stem cell collection). After an additional four cycles of lenalidomide (a total of 8 cycles), start the maintenance phase (lenalidomide days 1-21 every 28 days for two years or until your disease progresses).

Group Type: ACTIVE_COMPARATOR

Lenalidomide

Intervention Type: DRUG

Administered orally at a dose 25 mg daily on days 1-21 of each 28-day cycle.

Dexamethasone

Intervention Type: DRUG

Administered orally at a dose of 40 mg daily on days 1, 8, 15, 22 of each cycle.

Stem cell collection

Intervention Type: PROCEDURE

Peripheral stem cell collection will be performed at marrow recovery, usually when white blood cell (WBC) is \>2500 x 109 cells/liter; platelet count is \>20 x 103/mm3.

Cyclophosphamide

Intervention Type: DRUG

Subjects may receive up to the maximum recommended high-dose of cyclophosphamide at 4 gm/m2 intravenously.

Mesna

Intervention Type: DRUG

Mesna will be provided with the cyclophosphamide.

Interventions

Autologous peripheral blood stem cell transplant

Subjects deemed suitable by the principal investigator will undergo autologous peripheral blood stem cell transplantation on day 0.

Intervention Type: PROCEDURE

Lenalidomide

Administered orally at a dose 25 mg daily on days 1-21 of each 28-day cycle.

Intervention Type: DRUG

Dexamethasone

Administered orally at a dose of 40 mg daily on days 1, 8, 15, 22 of each cycle.

Intervention Type: DRUG

Stem cell collection

Peripheral stem cell collection will be performed at marrow recovery, usually when white blood cell (WBC) is \>2500 x 109 cells/liter; platelet count is \>20 x 103/mm3.

Intervention Type: PROCEDURE

Melphalan

Subjects undergoing autologous peripheral blood stem cell transplant will receive melphalan 200 mg/m2 intravenously on days -2 and -1 or only on day -2.

Intervention Type: DRUG

G-CSF

Subjects will receive G-CSF subcutaneously daily beginning on day 5 and until blood counts recover.

Intervention Type: DRUG

Cyclophosphamide

Subjects may receive up to the maximum recommended high-dose of cyclophosphamide at 4 gm/m2 intravenously.

Intervention Type: DRUG

Mesna

Mesna will be provided with the cyclophosphamide.

Intervention Type: DRUG

Other Intervention Names

CC-5013; Revlimid; Decadron; Hexadrol; Dexameth; Dexone; DXM; Stem Cell Mobilization; Evomela; Granulocyte-colony stimulating factor (CSF); Filgrastim; Cytophosphane; Mesnex

Eligibility 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 Immunoglobulin G (IgG) or .5 g/dL Immunoglobulin A (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.
• Eastern Cooperative Oncology Group (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
• Aspartate aminotransferase (AST)(SGOT) / alanine aminotransferase (ALT)(SGPT) < or = 2.5 X upper limit of normal (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 milli-international units per millilitre (mIU/mL) within 10 - 14 days prior to and again within 24 hours of prescribing lenalidomide and must either commit to continued abstinence or 2 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. International Normalized Ratio (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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Columbia University

OTHER

Sponsor Role: lead

Responsible Party

Suzanne Lentzsch, MD

Associate Clinical Professor of Clinical Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Suzanne Lentzsch, MD

Role: PRINCIPAL_INVESTIGATOR

Columbia University

Locations

Columbia University

New York, New York, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

AAAJ2355

Identifier Type: -

Identifier Source: org_study_id

NCT00777881

Identifier Type: -

Identifier Source: nct_alias