Lenalidomide (Revlimid®) Plus Low-dose Dexamethasone (Ld x 4 Cycles) Then Stem Cell Collection Followed by Randomization to Continued Ld or Stem Cell Transplantation (SCT) Plus Maintenance L

NCT ID: NCT00807599

Last Updated: 2019-03-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 67 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-12-10
• Study Completion Date: 2018-07-31

Brief Summary

The purpose of this study is to compare the effects, good and bad, of two ways to treat patients with standard-risk symptomatic multiple myeloma. Patients with standard-risk myeloma have myeloma with specific features: levels of 2 blood tests have to be in a specific range and there can be no myeloma tumors found outside of the bones or bone marrow, the areas where myeloma is usually discovered. In past clinical studies, patients with standard-risk myeloma have done well with intensive therapy in the form of stem cell transplant. But multiple myeloma is not curable and, although it may respond to standard treatments including stem cell transplant, myeloma always recurs.

Conditions

Multiple Myeloma

Study Design

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

Study Groups

Stem cell transplant x 1 or x 2

All patients on this study start with the same treatment, lenalidomide and dexamethasone by mouth. After patients have received 4 cycles of lenalidomide and dexamethasone and are within 2 weeks of completing stem cell collection, they are randomized (like the toss of a coin) to either :

• stem cell transplant right after collection
• continue lenalidomide and dexamethasone, saving stem cell transplant for a later time.

Group Type: EXPERIMENTAL

Stem cell transplant x 1 or x 2

Intervention Type: PROCEDURE

After 4 cycles of Ld, eligible patients will undergo stem cell mobilization and collection with standard-of-care cyclophosphamide and Neupogen (G-CSF) or with plerixafor G-CSF. Mobilization with cyclophosphamide is preferred, but plerixafor is also allowed. Ld will be held for at least 2 weeks prior to stem cell mobilization.

On the SCT arm, patients not achieving VGPR by 3 months after the 1st SCT will undergo a 2nd SCT. All patients, after one or two SCT, will receive maintenance L.

Continue lenalidomide and dexamethasone

All patients on this study start with the same treatment, lenalidomide and dexamethasone by mouth. After patients have received 4 cycles of lenalidomide and dexamethasone and are within 2 weeks of completing stem cell collection, they are randomized (like the toss of a coin) to either :

stem cell transplant right after collection

• continue lenalidomide and dexamethasone
• saving stem cell transplant for a later time.

Group Type: EXPERIMENTAL

lenalidomide and dexamethasone

Intervention Type: DRUG

Patients will then be randomized to continued Ld or high-dose melphalan with SCT. On the SCT arm patients not achieving VGPR by 3 months after the 1st SCT will undergo a 2nd SCT. All patients after one or two SCT, will receive maintenance L.

Interventions

Stem cell transplant x 1 or x 2

After 4 cycles of Ld, eligible patients will undergo stem cell mobilization and collection with standard-of-care cyclophosphamide and Neupogen (G-CSF) or with plerixafor G-CSF. Mobilization with cyclophosphamide is preferred, but plerixafor is also allowed. Ld will be held for at least 2 weeks prior to stem cell mobilization.

On the SCT arm, patients not achieving VGPR by 3 months after the 1st SCT will undergo a 2nd SCT. All patients, after one or two SCT, will receive maintenance L.

Intervention Type: PROCEDURE

lenalidomide and dexamethasone

Patients will then be randomized to continued Ld or high-dose melphalan with SCT. On the SCT arm patients not achieving VGPR by 3 months after the 1st SCT will undergo a 2nd SCT. All patients after one or two SCT, will receive maintenance L.

Intervention Type: DRUG

Other Intervention Names

In the initial 4 cycles of therapy, pts will receive oral lenalidomide at the; starting dose of 25mg on days 1-21 every 28 days (1 cycle) with dose; adjustments for creatinine clearance (CRCL) & dose reductions for toxicity.; Pts will receive low-dose oral dexamethasone at 40mg weekly on days 1, 8, 15 &; 22 of each 28-day cycle with dose reductions as below for toxicity (the weekly; dose could be split over 2 days in the week i.e. 20mg on days 1, 4, 8, 11, 15,; 18, 22, & 25 for better tolerance). For SCT, pts are adm to hosp. High-dose; melphalan is admin in a single dose on day -2 or split dose on days -3 & -2,; through a cvc. Melphalan doseadjustments are made for age & CRCL,. Pts with; CRCL,> 51ml/min receive melphalan at 200mg/m2. Pts with CRCL < 51ml/min; (to be evaluated within 2 weeks of SCT) will receive 140mg/m2. Pts > 70 years; old receive 140mg/m2 also. Each SCT in a tandem SCT is a clinically discrete; event & these rules of dose adjustment apply to each SCT. It is possible,; that pts will get different doses of melphalan in tandem SCT; In the initial 4 cycles of therapy, pts will receive oral lenalidomide at the; starting dose of 25mg on days 1-21 every 28 days (one cycle) with dose; adjustments for creatinine clearance and dose reductions. Pts will receive; low-dose oral dexamethasone at 40mg weekly on days 1, 8, 15 & 22 of each; 28-day cycle with dose reductions (the weekly dose could be split over 2 days; in the week i.e. 20mg on days 1, 4, 8, 11, 15, 18, 22, & 25 for better; tolerance). For continued Ld, pts will resume Ld at the last dose tolerated; during the initial 4 cycles, with prophylactics & dose reductions as indicated.; Lenalidomide will be continued until progression of disease, if as tolerated.; Low-dose dexamethasone will be continued for 1 year (from the start of initial; treatment), as tolerated. Dose adjustments will follow guidelines. Pts will; be seen every 3 months by their physician & their disease will be reassessed.; Pts will also have a CBC & pregnancy test performed monthly.

Eligibility Criteria

Inclusion Criteria

• Age ≥ 18 and ≤ 75
• Histologic and serologic findings from MSKCC confirming the diagnosis of multiple myeloma. Standard diagnostic criteria for multiple myeloma will be used, as per the revised International Myeloma Working Group diagnostic criteria.
• Patients must have symptomatic multiple myeloma without advanced organ damage (such as multiple fractures or advanced bone disease causing immobilization, renal failure, spinal cord compression, or organ compromise due to soft tissue plasmacytoma). If immediate therapy with radiation and high-dose steroids (eg, for cord compression) or with bortezomib-based therapy (eg, for renal failure) is required, the patient is not eligible for this trial.
• Patients may have received 1 cycle of prior therapy with dexamethasone for multiple myeloma.
• Adequate organ function is required, defined as follows:
• ANC ≥ 1,500/μl and platelets ≥ 100,000/μl (unless low ANC and platelets are due to multiple myeloma)
• Serum bilirubin ≤ 2.0 mg/dl
• AST, ALT and alkaline phosphatase < 3 times the upper limit of laboratory normal
• Adequate renal function as assessed by calculated creatinine using Cockcroft-Gault estimation of CrCl (see Appendix I): Subjects must have calculated creatinine clearance ≥ 30ml/min by Cockcroft-Gault formula
• Performance status (ECOG) ≤ 2 (Appendix E).
• Eligible for SCT with LVEF ≥ 50% by MUGA or ECHO, and diffusing capacity > 50% predicted by pulmonary function testing
• Ability to understand the investigational nature of this study and to give informed consent
• All study participants must be registered into the mandatory Revlimid REMS® program, and be willing and able to comply with the requirements the of Revlimid REMS® program
• 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 prior to prescribing lenalidomide for cycle 1 (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 not to father a child and agree to use a latex condom during sexual contact with females of child bearing potential even if they have had a successful vasectomy. See Appendix C: Risks of Fetal Exposure, Pregnancy Testing Guidelines and Acceptable Birth Control Methods.
• Able to take aspirin 325mg or 81mg daily as prophylactic anticoagulation (patients intolerant to ASA may use Coumadin or low molecular weight heparin).

Exclusion Criteria

• Prior treatment for myeloma except for one cycle of dexamethasone
• History of thromboembolic disease within the past 6 months regardless of anticoagulation
• Myocardial infarction within 6 months prior to enrollment, or New York Hospital Association (NYHA) Class III or IV heart failure (see APPENDIX F), uncontrolled angina, severe uncontrolled ventricular arrhythmias, electrocardiographic evidence of acute ischemia or active conduction system abnormalities.
• Pregnant or breast-feeding women are excluded due to the potential teratogenicity of lenalidomide.
• Concurrent active malignancy other than non-melanoma skin cancers or carcinoma-insitu of the cervix, or presence of myelodysplastic or myeloproliferative disease. Patients with prior malignancies with a disease-free interval of ≥ 5 years are eligible.
• Patients who have had prior malignancies within the past 5 years but are considered to be "cured" with a low likelihood of recurrence may be eligible at the discretion of the Principal Investigator.
• Active hepatitis B or C infection
• HIV 1 or 2 positivity
• Any other medical condition or laboratory evaluation that, in the treating physician's or principal investigator's opinion, makes the patient unsuitable to participate in this clinical trial

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Tufts Medical Center

OTHER

Sponsor Role: collaborator

Lahey Clinic

OTHER

Sponsor Role: collaborator

Memorial Sloan Kettering Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Hani Hassoun, MD

Role: PRINCIPAL_INVESTIGATOR

Memorial Sloan Kettering Cancer Center

Locations

Memoral Sloan Kettering Cancer Center

Basking Ridge, New Jersey, United States

Memorial Sloan-Kettering Cancer Center @ Suffolk

Commack, New York, United States

Memorial Sloan Kettering West Harrison

Harrison, New York, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Memorial Sloan Kettering at Mercy Medical Center

Rockville Centre, New York, United States

Memoral Sloan Kettering Cancer Center at Phelps

Sleepy Hollow, New York, United States

Memorial Sloan Kettering Cancer Center at Phelps Memorial Hospital Center

Sleepy Hollow, New York, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

http://www.mskcc.org

Memorial Sloan Kettering Cancer Center

Other Identifiers

08-121

Identifier Type: -

Identifier Source: org_study_id