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

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2012 by Columbia University
Sponsor:
Information provided by (Responsible Party):
Suzanne Lentzsch, MD, Columbia University
ClinicalTrials.gov Identifier:
NCT01731886
First received: November 19, 2012
Last updated: NA
Last verified: November 2012
History: No changes posted
  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: Lenalidomide and dexamethasone for four 28-day cycles with or without autologous peripheral blood stem cell transplant.
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:
  • 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:
  • 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: 114
Study Start Date: August 2012
Estimated Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm A
Lenalidomide and dexamethasone for four 28-day cycles followed by autologous peripheral blood stem cell transplant followed by maintenance.
Procedure: Lenalidomide and dexamethasone for four 28-day cycles with or without autologous peripheral blood stem cell transplant.
Other Names:
  • Drug: Lenalidomide
  • -Lenalidomide (25 mg daily) is taken orally (by mouth) in the morning on days 1 through 21 of each cycle.
  • Other Names:
  • -CC-5013
  • -Revlimid
  • Drug: Dexamethasone
  • -Dexamethasone (40 mg daily) is also taken orally (by mouth) on days 1, 8, 15, and 22 of each cycle.
Active Comparator: Arm B
Lenalidomide and dexamethasone for six to eight 28-day cycles followed by maintenance.
Procedure: Lenalidomide and dexamethasone for four 28-day cycles with or without autologous peripheral blood stem cell transplant.
Other Names:
  • Drug: Lenalidomide
  • -Lenalidomide (25 mg daily) is taken orally (by mouth) in the morning on days 1 through 21 of each cycle.
  • Other Names:
  • -CC-5013
  • -Revlimid
  • Drug: Dexamethasone
  • -Dexamethasone (40 mg daily) is also taken orally (by mouth) on days 1, 8, 15, and 22 of each cycle.

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:

  • Subjects must have 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. (See Appendix E)
  • Bone marrow plasmacytosis with > or = 10% plasma cells, or sheets of plasma cells or a biopsy-proven plasmacytoma which must be obtained up to 6 weeks prior to registration.
  • 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 which must be obtained within 4 weeks prior to registration. If both serum and urine monoclonal components are present, both must be followed in order to evaluate response.

Serum free light chains (FLC) should be measured with each SPEP and is recommended to monitor for subjects with light chain disease. Non-secretory MM subjects will be included if they have measurable parameters to follow, e.g. extramedullary plasmocytoma or measurable bone marrow infiltration, or FLC level ≥ 10 mg/dL (≥ 100 mg/L) provided serum FLC ratio is abnormal.29 Both SPEP and UPEP must be performed within 28 days prior to registration. For subjects presenting with aggressive disease or requiring immediate intervention, up to two weeks or two pulses of high dose dexamethasone (40 mg x 4 days = 1 pulse) is allowed, prior to the start of study treatment. If dexamethasone is given at reduced dose, the total allowed dose is 320 mg prior to enrollment. Prior systemic glucocorticosteroid use for the treatment of non-malignant disorders is permitted; concurrent use after subject is on study treatment of non-malignant disorders is permitted; concurrent use for non-malignant disorders after a subject is on study treatment is permitted, but should be restricted to the equivalent of prednisone 10mg per day. Prior or concurrent topical or localized glucocorticosteroid therapy to treat non-malignant comorbid disorders is permitted.

Subjects should not have received any radiation for the preceding 4 weeks before entry onto the study. Exception: local radiation therapy for symptomatic bone lesions (eg, uncontrolled pain or high risk of pathologic fracture), superior or inferior vena cava syndrome, spinal cord compression or extramedullary soft tissue lesions, as clinically indicated to relieve severe symptoms. Subjects with prior solitary plasmacytoma treated with radiation therapy with curative intent are eligible if the disease has now progressed to active multiple myeloma meeting all the eligibility criteria for this protocol.

  • Age >18 years.
  • Life expectancy of greater than 12 months.
  • ECOG performance status <2 (Karnofsky >60%) (See Appendix B).
  • Subjects must have adequate organ and marrow function as defined below, obtained within 4 weeks prior to registration:

Hgb > 9 g/dL (which may be supported by transfusion or growth factors) Absolute Neutrophil Count >1,500/ ml (use of growth factors to meet screening requirements is not permitted) Platelets >50,000/mm3 (administration of platelet transfusions during screening to meet eligibility criteria is not allowed. However, platelet transfusions may be administered as clinically indicated to subjects in both treatment arms who have begun lenalidomide therapy) Total Bilirubin <1.5 mg/dL AST(SGOT) / ALT(SGPT) <2.5 X institutional upper limit of normal Creatinine <2.0 mg/dL (subjects with creatinine > 2 should receive lenalidomide according to the dosing schedule (Appendix C).

Creatinine Clearance >50 ml/min (estimated). Subjects with creatinine clearance < 50 ml/min should receive lenalidomide according to the dosing schedule (Appendix C).

  • Ability to understand and the willingness to sign a written informed consent document. Subject must be informed of the investigational nature of this study.
  • Subjects with a history of prior malignancy are eligible provided there is no active malignancy and a low expectation of recurrence within 6 months.
  • Subjects 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.
  • Subjects who are 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.
  • All study participants must be registered into the mandatory RevAssist® program, and be willing and able to comply with the requirements of RevAssist®.
  • 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 (prescriptions must be filled within 7 days) and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking lenalidomide. FCBP must also agree to ongoing pregnancy testing. Males must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy. (See Appendix D: Risks of Fetal Exposure, Pregnancy Testing Guidelines and Acceptable Birth Control Methods)

Exclusion Criteria:

  • Patients who have had chemotherapy or radiotherapy for multiple myeloma prior to entering the study. Patients should not have received any radiation for the preceding 4 weeks before entry onto the study. Exception: local radiation therapy for symptomatic bone lesions (e.g., uncontrolled pain or high risk of pathologic fracture), superior or inferior vena cava syndrome, spinal cord compression or extramedullary soft tissue lesions, as clinically indicated to relieve severe symptoms. Patients with prior solitary plasmacytoma treated with radiation therapy with curative intent are eligible if the disease has now progressed to active multiple myeloma meeting all the eligibility criteria for this protocol.
  • Patients receiving any other investigational agents or therapy within 28 days of baseline.
  • Patients with known brain metastases will be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
  • Patients who are pregnant or breast feeding. Due to the potential teratogenic properties of lenalidomide, the use of this drug in patients that are pregnant is absolutely contraindicated. Further, all women of childbearing potentialFCBP and sexually active males must agree to avoid conception while participating in this study. Specifically, women of childbearing potentialFCBP must either agree to refrain from sexual intercourse or employ a dual method of contraception, one of which is highly effective (IUD, birth control pills, tubal ligation or partners vasectomy), and another additional method (condom, diaphragm, or cervical cap) for 4 weeks prior to receiving lenalidomide, and for four weeks after discontinuing this therapy. Sexually active males cannot participate unless they agree to use a condom (even if they have undergone a prior vasectomy) while having intercourse with a woman of child bearing potentialFCBP while taking lenalidomide and for four weeks after stopping treatment. Women of child bearing potentialFCBP (those who have not had a hysterectomy or the absence of menstrual periods for at least 24 consecutive months) must have a negative pregnancy test 10-14 days prior to the initiation of therapy and a repeat negative pregnancy test 24 hours prior to the initiation of lenalidomide.
  • Inability to comply with study and/or follow-up procedures.
  • Patients with a history of previous deep vein thrombosisDVT or pulmonary embolismPE must be on anticoagulation therapy with low molecular weight heparin or warfarin at therapeutic dosages (e.g. INR 2-3).
  • If a patient 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.
  • Patients with smoldering myeloma or monoclonal gammopathy of undetermined significance (MGUS) are not eligible.
  • Patients must not have active, uncontrolled infection.
  • Patients must not have active, uncontrolled seizure disorder. Patients must have had no seizures in the last 6 months.
  • Concurrent use of other anti-cancer agents or treatments.
  • Known positive for HIV or infectious hepatitis, type B or C.
  • Known hypersensitivity to thalidomide.
  • Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study.
  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

Contacts
Contact: Suzanne Lentzsch, MD (646)317-4805 sl3440@columbia.edu

Locations
United States, New York
Columbia University Recruiting
New York, New York, United States, 10032
Principal Investigator: Suzanne Lentzsch, MD         
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: November 19, 2012
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 November 20, 2014