- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01954784
Lenalidomide After Donor Stem Cell Transplant and Bortezomib in Treating Patients With High Risk Multiple Myeloma
A Study of Low-dose Lenalidomide After Non-myeloablative Allogeneic Stem Cell Transplant With Bortezomib as GVHD Prophylaxis in High Risk Multiple Myeloma
Study Overview
Status
Conditions
Detailed Description
PRIMARY OBJECTIVES:
I. Identify the maximal tolerated dose (MTD) and safety of lenalidomide up to 10mg following non-myeloablative allogeneic stem cell transplant for multiple myeloma.
SECONDARY OBJECTIVES:
I. Assess safety and tolerability of weekly bortezomib following non-myeloablative allogeneic stem cell transplant.
II. Obtain estimates of non-relapse mortality. III. Obtain estimates of acute and chronic graft-versus-host disease (GVHD). IV. Obtain estimates of 1 year relapse and survival.
OUTLINE: This is a dose-escalation study of lenalidomide.
PREPARATIVE REGIMEN: Patients receive fludarabine phosphate on days -5 to -3 and undergo total body irradiation (TBI) on day -1.
TRANSPLANT: Patients undergo allogeneic hematopoietic stem cell transplant (SCT) on day 0.
GVHD PROPHYLAXIS: Patients receive standard GVHD prophylaxis comprising cyclosporine orally (PO) twice daily (BID) beginning on day -1 with taper beginning on day 100, mycophenolate mofetil PO BID on days 1-56, and bortezomib subcutaneously (SC) weekly from day 1 to day 91.
MAINTENANCE THERAPY: Beginning on day 100, patients receive lenalidomide PO daily on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up monthly for 1 year post-transplant.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
Ohio
-
Cleveland, Ohio, United States, 44195
- Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Symptomatic multiple myeloma by International Myeloma Working Group (IMWG) criteria according to the most recent updated version (International Myeloma Workshop [IMW] meeting in Paris 2011)
- Must have received at least 3 of the following classes of anti-myeloma agents either alone or in combination: glucocorticoids, immunomodulatory drugs including thalidomide, proteasome inhibitors, alkylating chemotherapy, or anthracyclines
Must meet any of these criteria for high risk disease:
- Relapse or progressive disease according to uniform response criteria within 2 years after starting first-line therapy or within 2 years after autologous stem cell transplant
- Failure to achieve partial response (PR) within 6 months of staring first-line therapy
- Presence of high risk cytogenetic features (t(14;16), t(14;20), deletion 17p)
- Chromosome 14 translocations other than to chromosome 11
- Chromosome 1p deletion and 1q amplification
- MyPRS gene expression score equal or higher than 45.2
- High risk 70 gene expression profile (MyPRS GEP70TM)
- Any other high risk genetic profile that is determined by future IMWG consensus or by internal myeloma panel consensus; for the latter, any additional criteria will be submitted as an addendum
- Diagnosis with multiple myeloma between the ages of 18-50
- Must have achieved at least a minor response to any previous regimen according to adapted European Group for Blood and Marrow Transplantation (EBMT) criteria
- Must have suitable matched sibling or matched unrelated donor for stem cell source
- Must be transplant-eligible per institution guidelines
- Must have estimated glomerular filtration rate (eGFR) by Modification of Diet in Renal Disease (MDRD) formula or Cockroft-Gault formula of 50mL/min or higher
- All study participants must be registered into the mandatory Revlimid REMS® program, and be willing and able to comply with the requirements of Revlimid REMS®
- Females of childbearing potential must have negative serum or urine pregnancy test and use acceptable birth control methods
- Able to take aspirin daily as prophylactic anticoagulation (patients intolerant to acetylsalicylic acid [ASA] may use warfarin or low molecular weight heparin)
Exclusion Criteria:
Participants must not:
- Have known hypersensitivity to thalidomide or lenalidomide
- Have progressive disease at the time of transplant
- Uncontrolled concurrent significant medical or psychological co-morbidity
- Grade 3 peripheral neuropathy
- Known seropositive for or active viral infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV); patients who are seropositive because of hepatitis B virus vaccine are eligible
- Be females who are pregnant
- Recent (within 3 years) history of other malignancies, excluding basal cell carcinoma or squamous cell carcinoma of the skin
- Be currently enrolled in another investigational treatment protocol
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Treatment (nonmyeloablative alloHSCT, lenalidomide)
PREPARATIVE REGIMEN: Patients receive fludarabine phosphate on days -5 to -3 and undergo TBI on day -1. TRANSPLANT: Patients undergo allogeneic hematopoietic SCT on day 0. GVHD PROPHYLAXIS: Patients receive standard GVHD prophylaxis comprising cyclosporine PO BID beginning on day -1 with taper beginning on day 100, mycophenolate mofetil PO BID on days 1-56, and bortezomib SC weekly from day 1 to day 91. MAINTENANCE THERAPY: Beginning on day 100, patients receive lenalidomide PO daily on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. |
Given PO
Other Names:
Correlative studies
Other Names:
Undergo TBI
Other Names:
Given PO
Other Names:
Given PO
Other Names:
Given SC
Other Names:
Undergo nonmyeloablative allogeneic hematopoietic SCT
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
MTD of lenalidomide defined as one dose level below the dose in which 2 or more patients at a specified dose level experience dose limiting toxicity (DLT) according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (v. 4.0)
Time Frame: Day 128 post-transplant
|
Day 128 post-transplant
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Safety assessed by evaluating the incidence of toxicity according to CTCAE v. 4.0
Time Frame: Up to day 100
|
Up to day 100
|
Incidence of acute GVHD according to Center for International Blood and Marrow Transplant Research (CIBMTR)
Time Frame: 1 year
|
1 year
|
Incidence of chronic GVHD according to National Institutes of Health (NIH)
Time Frame: 1 year
|
1 year
|
Time to deaths without relapse/recurrence
Time Frame: 1 year
|
1 year
|
Progression-free survival
Time Frame: From study entry to progression as defined by international response criteria or death of any cause, whichever comes first, assessed at 1 year
|
From study entry to progression as defined by international response criteria or death of any cause, whichever comes first, assessed at 1 year
|
Overall survival
Time Frame: From study entry to death from any cause, assessed at 1 year
|
From study entry to death from any cause, assessed at 1 year
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Hien K Liu, MD, Case Comprehensive Cancer Center
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Cardiovascular Diseases
- Vascular Diseases
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Immunoproliferative Disorders
- Hematologic Diseases
- Hemorrhagic Disorders
- Hemostatic Disorders
- Paraproteinemias
- Blood Protein Disorders
- Multiple Myeloma
- Neoplasms, Plasma Cell
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Enzyme Inhibitors
- Antirheumatic Agents
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Angiogenesis Inhibitors
- Angiogenesis Modulating Agents
- Growth Substances
- Growth Inhibitors
- Dermatologic Agents
- Anti-Bacterial Agents
- Antibiotics, Antineoplastic
- Antifungal Agents
- Antitubercular Agents
- Antibiotics, Antitubercular
- Calcineurin Inhibitors
- Lenalidomide
- Bortezomib
- Fludarabine
- Fludarabine phosphate
- Mycophenolic Acid
- Cyclosporine
- Cyclosporins
Other Study ID Numbers
- CASE1A13 (Other Identifier: Case Comprehensive Cancer Center)
- P30CA043703 (U.S. NIH Grant/Contract)
- NCI-2013-01777 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Stage I Multiple Myeloma
-
Fred Hutchinson Cancer Research Center/University...National Cancer Institute (NCI)CompletedStage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
-
Mayo ClinicCompletedMultiple Myeloma | Stage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
-
National Cancer Institute (NCI)TerminatedStage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
-
National Cancer Institute (NCI)CompletedStage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
-
City of Hope Medical CenterCompletedStage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
-
University of WashingtonNational Cancer Institute (NCI)TerminatedStage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
-
Fred Hutchinson Cancer CenterNational Cancer Institute (NCI)CompletedStage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
-
Barbara Ann Karmanos Cancer InstituteNational Cancer Institute (NCI)TerminatedStage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
-
National Cancer Institute (NCI)CompletedStage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
-
Lawson Health Research InstituteThe Ottawa Hospital; Hamilton Health Sciences Corporation; Dalhousie University; Niagara Health SystemActive, not recruitingMultiple Myeloma in Relapse | Multiple Myeloma With Failed Remission | Multiple Myeloma Stage I | Multiple Myeloma Progression | Multiple Myeloma Stage II | Multiple Myeloma Stage IIICanada
Clinical Trials on lenalidomide
-
Sidney Kimmel Comprehensive Cancer Center at Johns...TerminatedMyelodysplastic SyndromeUnited States
-
Grupo Español de Linfomas y Transplante Autólogo...Celgene Corporation; Dynamic Science S.L.; Thermo Fisher Scientific, IncCompleted
-
Celgene CorporationICON Clinical ResearchCompletedMyelodysplastic SyndromesGermany, Israel, United Kingdom, Spain, Belgium, Italy, France, Netherlands, Sweden
-
Boston VA Research Institute, Inc.Celgene Corporation; Edward Hines Jr. VA Hospital; Michael E. DeBakey VA Medical... and other collaboratorsCompletedMultiple MyelomaUnited States
-
Swiss Group for Clinical Cancer ResearchTerminatedLymphomaSwitzerland, Norway, Sweden
-
Dana-Farber Cancer InstituteBeth Israel Deaconess Medical Center; Genentech, Inc.; Brigham and Women's Hospital and other collaboratorsTerminatedWaldenstrom's MacroglobulinemiaUnited States
-
University Hospital, ToulouseCelgene Corporation; Janssen-Cilag Ltd.Completed
-
CelgeneCompletedRelapsed or Refractory Chronic Lymphocytic LeukemiaUnited States, Canada, United Kingdom, France, Germany, Spain, Italy, Sweden
-
Groupe Francophone des MyelodysplasiesUnknownMyelodysplastic SyndromesFrance