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

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by Memorial Sloan-Kettering Cancer Center
Sponsor:
Collaborators:
Tufts Medical Center
Lahey Clinic
Information provided by (Responsible Party):
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT00807599
First received: December 11, 2008
Last updated: June 12, 2014
Last verified: June 2014
  Purpose

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.


Condition Intervention Phase
Multiple Myeloma
Procedure: Stem cell transplant x 1 or x 2
Drug: lenalidomide and dexamethasone
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Clinical Trial for Untreated Patients With Multiple Myeloma Eligible for Stem Cell Transplant: 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

Resource links provided by NLM:


Further study details as provided by Memorial Sloan-Kettering Cancer Center:

Primary Outcome Measures:
  • To determine the progression free survival (PFS) rate at 2 years after enrollment in untreated patients with multiple myeloma. [ Time Frame: conclusion of study ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To assess the CR+VGPR rate at 2 and 3 years [ Time Frame: conclusion of study ] [ Designated as safety issue: No ]
  • To assess overall myeloma response rates at 2 and 3 years [ Time Frame: conclusion of study ] [ Designated as safety issue: No ]
  • To assess overall survival [ Time Frame: conclusion of study ] [ Designated as safety issue: No ]

Estimated Enrollment: 62
Study Start Date: December 2008
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Procedure: 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.

Other 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
Experimental: 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.
Drug: 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.
Other 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 (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

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age ≥ or = to 18 and < or = to 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 International Myeloma Foundation consensus guidelines.
  • 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 ≥ or = to 1,500/μl and platelets≥ or = to 100,000/μl (unless low ANC and platelets are due to multiple myeloma)
  • Serum bilirubin ≤ or = to 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) ≤ or = to 2 (Appendix E).
  • Eligible for SCT with LVEF > or = to 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 ≥ or = to 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
  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: NCT00807599

Contacts
Contact: Hani Hassoun, MD 212-639-3228
Contact: Heather Landau, MD 212-639-8808

Locations
United States, New Jersey
Memoral Sloan Kettering Cancer Center Recruiting
Basking Ridge, New Jersey, United States
Contact: Hani Hassoun, MD    212-639-3228      
United States, New York
Memorial Sloan-Kettering Cancer Center @ Suffolk Recruiting
Commack, New York, United States, 11725
Contact: Hani Hassoun, MD    212-639-3228      
Memorial Sloan-Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Hani Hassoun, MD    212-639-3228      
Contact: , MD         
Principal Investigator: Hani Hassoun, MD         
Memorial Sloan-Kettering at Mercy Medical Center Recruiting
Rockville Centre, New York, United States
Contact: Hani Hassoun, MD    212-639-3228      
Memoral Sloan Kettering Cancer Center at Phelps Recruiting
Sleepy Hollow, New York, United States, 10591
Contact: Hani Hassoun, MD    212-639-3228      
Memorial Sloan-Kettering Cancer Center at Phelps Memorial Hospital Center Recruiting
Sleepy Hollow, New York, United States, 10591
Contact: Hani Hassoun, MD    212-639-3228      
Sponsors and Collaborators
Memorial Sloan-Kettering Cancer Center
Tufts Medical Center
Lahey Clinic
Investigators
Principal Investigator: Hani Hassoun, MD Memorial Sloan-Kettering Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT00807599     History of Changes
Other Study ID Numbers: 08-121
Study First Received: December 11, 2008
Last Updated: June 12, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Memorial Sloan-Kettering Cancer Center:
CYCLOPHOSPHAMIDE (CYTOXAN)
DEXAMETHASONE
G-CSF
Lenalidomide
MELPHALAN
PEG-FILGRASTIM (NEULASTA)
08-121

Additional relevant MeSH terms:
Neoplasms, Plasma Cell
Multiple Myeloma
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Cyclophosphamide
Melphalan
Thalidomide
Lenalidomide
Dexamethasone
Dexamethasone acetate
Dexamethasone 21-phosphate
BB 1101
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents

ClinicalTrials.gov processed this record on July 23, 2014