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

Multiple Myeloma Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00777881
• Other study ID #: UPCI 07-134
• Status: Active, not recruiting
• Phase: Phase 4
• First received: October 21, 2008
• Last updated: March 24, 2015
• Start date: January 2008
• Est. completion date: January 2017

Study information

• Verified date: March 2015
• Source: University of Pittsburgh
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 114
• Est. completion date: January 2017
• Est. primary completion date: January 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria

• Patients 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 (SPEP) or > 200 mg of monoclonal light chain on a 24 hour urine protein electrophoresis (UPEP) 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 patients with light chain disease. Non-secretory MM patients 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.

• Both SPEP and UPEP must be performed within 28 days prior to registration.

• For patients 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 patient is on study treatment of non-malignant disorders is permitted; concurrent use for non-malignant disorders after a patient 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.

• 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.

• Age >18 years

• Life expectancy of greater than 12 months.

• ECOG performance status <2 (Karnofsky >60%).

• Patients 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. Patients with creatinine > 2 should receive lenalidomide according to the dosing schedule creatinine clearance >50 ml/min (estimated). Patients with creatinine clearance < 50 ml/min should receive lenalidomide according to the dosing schedule. Contact Transplant team from Hillman Cancer Center to check eligibility for transplant before randomization.

• Ability to understand and the willingness to sign a written informed consent document. Patient must be informed of the investigational nature of this study.

• Patients with a history of prior malignancy are eligible provided there is no active malignancy and a low expectation of recurrence within 6 months.

• Patients 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.

• Patients who are eligible for transplant with an age up to and including 75 years. Patients 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. Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy. See Appendix: 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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• Lenalidomide
• Lenalidomide (25 mg daily) is taken orally (by mouth) in the morning on days 1 through 21 of each cycle.
• Dexamethasone
• Dexamethasone (40 mg daily) is also taken orally (by mouth) on days 1, 8, 15, and 22 of each cycle.

Locations

Country	Name	City	State
United States	Hillman Cancer Center	Pittsburgh	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
University of Pittsburgh

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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		3 years	Yes