Celgene High Risk Multiple Myeloma (MM) Revlimid Induction and Maintenance Therapy
This study has been completed.
Information provided by (Responsible Party):
Cristina Gasparetto, Duke University Medical Center
First received: June 3, 2008
Last updated: August 14, 2014
Last verified: August 2014
The purpose of this study is to evaluate the effectiveness of induction therapy with lenalidomide and low dose dexamethasone followed by sequential low dose bortezomib followed by low dose Melphalan and Prednisone, then followed by low dose lenalidomide for multiple cycles in subjects with high risk Multiple Myeloma (MM). The primary objective is to evaluate the efficacy as measured by the progression free survival (PFS) at 2 years of low dose sequential therapy following four cycles of induction therapy with lenalidomide/low-dose dexamethasone in subjects with symptomatic high risk multiple myeloma, who have received no prior treatment. A total of 35 subjects were estimated to be accrued to this Phase II trial over a period of subjects who are still progression-free at 2 years. Two years will be as measured from date of registration to the trial. Progression will include disease progression (DP) as well as death due to any cause. Data will be analyzed and reported by the PI after 1 and 2 years of initiation of the study. All subsequent data collected may be analyzed and reported in a follow-up clinical report. The PI and independent reviewers will meet to review the efficacy and safety data and determine a risk/benefit analysis in this subject population.
Drug: Lenalidomide Induction
Drug: Sequential Maintenance Therapy
||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
||Lenalidomide and Low Dose Dexamethasone Induction Therapy Followed by Low Dose Melphalan, Prednisone, Lenalidomide and Bortezomib Sequential Maintenance Therapy for Newly Diagnosed High-risk Multiple Myeloma
Primary Outcome Measures:
- Progression Free Survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
Progression free survival (PFS) is defined for all subjects as the time from the date of initiation of treatment to the date of first documentation of relapse, progression, or death due to any cause. Full restaging was performed at 6, 12, 18, 24, 36, 48, 60, 72 months). PFS survival will be estimated and plotted with the Kaplan-Meier method. The median will be calculated with 95% confidence intervals.
Secondary Outcome Measures:
- Time to Response [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
Time to response will be measured in the population of subjects with a confirmed response as the time from the date of initiation of treatment to the date of the first documentation of a confirmed response. Full restaging was performed at 6, 12, 18, 24, 36, 48, 60, 72 months). Time to response will be estimated and plotted with the Kaplan-Meier method. The median will be calculated with 95% confidence intervals.
- Overall Survival [ Time Frame: 6 years ] [ Designated as safety issue: No ]
Overall survival is defined as the time from the date of initiation of treatment to the date of death due to any cause. Overall response rate will be estimated with its 80% confidence interval, and the numbers of subjects achieving a sustained complete response (sCR), complete response (CR), very good partial response (VGPR), partial response (PR), or stable disease (SD) will be tabulated. Overall survival will be estimated and plotted with the Kaplan-Meier method. The median will be calculated with 95% confidence intervals.
- Time to Progression [ Time Frame: 6 years ] [ Designated as safety issue: Yes ]
Time to progression (TTP) is defined for all patients as the time from initiation of treatment to disease progression with deaths owing to causes other than progression not counted as events, but censored (Durie et al., 2006).
- Duration of Response [ Time Frame: 6 years ] [ Designated as safety issue: No ]
The duration of response, defined only among the responders, is measured from start of achieving Partial Response (PR) [first observation of PR before confirmation] to the time of disease progression, with deaths owing to causes other than progression not counted as events, but censored (Durie et al., 2006). Duration of response will be estimated and plotted with the Kaplan-Meier method. The median will be calculated with 95% confidence intervals.
| Study Start Date:
| Study Completion Date:
| Primary Completion Date:
||December 2012 (Final data collection date for primary outcome measure)
Experimental: High-risk Multiple Myeloma
Lenalidomide Induction (with Low Dose Dexamethasone) Therapy Followed by Low Dose Melphalan, Prednisone, Lenalidomide and Bortezomib Sequential Maintenance Therapy
Drug: Lenalidomide Induction
Induction: Lenalidomide 25 mg daily on Days 1-21 followed by 7 day rest and Dexamethasone 40 mg by mouth (po) daily on Days 1, 8, 15 and 22 every 28 days for 4 cycles.
Other Name: Lenalidomide
Drug: Sequential Maintenance Therapy
Subjects who achieve >partial response (PR) following induction therapy will receive repeating triplet cycles of alternating low dose therapy until progression, poor tolerance or toxicity. Subjects who complete 24 months of maintenance will be removed from study unless they achieved > stable disease (SD) from maintenance (per discussion with physician):
- 325 mg aspirin for deep vein thrombosis (DVT) prophylaxis
- Cycle 1, 4, 7, etc. - bortezomib 1.3 mg/m2 on day 1 and 8 of a 28-day cycle
- Cycle 2, 5, 8 etc. - Melphalan 6 mg/m2 by mouth (po) daily on Days 1-7
- Prednisone 60 mg /m2 po daily on Days 1-7 of a 28-day cycle
- Cycle 3, 6, 9, etc. Lenalidomide 10 mg po daily on Days 1-21 of a 28 day cycle.
- Lenalidomide (Revlimid)
- Bortezomib (Velcade)
|Ages Eligible for Study:
||18 Years and older
|Genders Eligible for Study:
|Accepts Healthy Volunteers:
- Understand and voluntarily sign an informed consent form.
- Age 18 years or older at the time of signing the consent.
- Able to adhere to the study visit schedule and other protocol requirements.
Multiple myeloma (MM) diagnosed according to the following standard criteria:
- Monoclonal plasma cells in bone marrow ≥10% and/or presence of biopsy-proven plasmacytoma
- Monoclonal protein present in serum and/or urine Myeloma-related organ dysfunction (1 or more) (C) Calcium elevation in blood (serum calcium >10.5 mg/L or ULN) (R) Renal insufficiency (SCr >2 mg/dL) (A) Anemia (hemoglobin <10 g/dL or 2g <normal) (B) Lytic bone lesions or osteoporosis
- Measurable disease requiring systemic therapy.
High risk multiple myeloma defined by the presence of one or more of the following:
- Deletion of chromosome 13 by metaphase analysis (standard cytogenetics)
- deletion of 17p13 (p53) by Fluorescence in situ hybridization (FISH) or metaphase analysis
- t(4;14) by FISH
- t(14;16) by FISH
- t(8;14) by FISH
- t(14;20) by FISH
- hypodiploidy detected by FISH or metaphase analysis
- any complex cytogenetic abnormality detected by metaphase analysis, with the exception of hyperdiploidy
- No previous treatment with systemic therapy or radiation therapy lasting more than 4 weeks duration.
- At least 7 days since date of last radiation or systemic treatment for MM.
- Eastern Cooperative Oncology Group (ECOG) performance status of < or =2 at study entry.(0=Fully active; 1=Restricted but ambulatory; 2=Ambulatory but unable to work)
- All study participants must be registered into the mandatory RevAssist® program, and willing and able to comply with the requirements.
- Females of childbearing potential (FCBP) must have negative pregnancy test with a sensitivity of >/=50 milli-International unit (mIU)/mL within 10-14 days prior to and within 24 hours of prescribing lenalidomide and must use 2 acceptable methods of birth control, one highly effective method and one other effective method AT THE SAME TIME, >4 weeks before 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 even if he has had a successful vasectomy, if partner is FCBP.
- Disease free of prior malignancies for >5 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma "insitu" of the cervix or breast
- Able to take 325 mg aspirin daily as prophylactic anticoagulation for the duration of protocol therapy.
- Receive concomitant therapy with bisphosphonates if bony lesions are present at time of enrollment.
- Any serious medical condition, laboratory abnormality, or psychiatric illness to prevent the subject from signing the consent.
- Pregnant or breast feeding females.
- Any condition which places the subject at unacceptable risk or confounds the ability to interpret data from the study.
Abnormal laboratory test results within these ranges:
- Absolute neutrophil count < 1.0 x 109/L
- Platelet count < 50 x 109/L (Subjects with severe pancytopenia (not meeting the above criteria) due to myeloma involvement of > 70% bone marrow are eligible)
- Serum creatinine > 2.5 mg/dL or ≥ 3.0 mg/dL if due to multiple myeloma.
- Total bilirubin > 2.0 mg/dl
- History of allergy to any of the study medications, their analogues, or excipients in the various formulations
- Concurrent use of other anti-cancer agents or treatments.
- Known HIV positivity
- Known Active Hepatitis A, B or C
- Erythema nodosum characterized by a desquamating rash while taking thalidomide or similar drug.
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: NCT00691704
|Duke University Medical Center
|Durham, North Carolina, United States, 27710 |
||Cristina Gasparetto, MD
||David Hurd, MD
||Wake Forest School of Medicine
||Peter M Voorhees, MD
||UNC Hospitals, University of North Carolina - Chapel Hill
||Jeffrey A. Zonder, MD
||Karmanos Cancer Center, Wayne State University
||Cristina Gasparetto, Associate Professor of Medicine, Duke University Medical Center
History of Changes
|Other Study ID Numbers:
|Study First Received:
||June 3, 2008
|Results First Received:
||March 4, 2014
||August 14, 2014
||United States: Institutional Review Board
Keywords provided by Duke University:
Additional relevant MeSH terms:
ClinicalTrials.gov processed this record on May 01, 2016
Neoplasms, Plasma Cell
Blood Protein Disorders
Immune System Diseases
Neoplasms by Histologic Type
Angiogenesis Modulating Agents
Antineoplastic Agents, Alkylating
Antineoplastic Agents, Hormonal