Lenalidomide After Donor Stem Cell Transplant and Bortezomib in Treating Patients With High Risk Multiple Myeloma

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2016 by Case Comprehensive Cancer Center
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
First received: September 27, 2013
Last updated: February 9, 2016
Last verified: February 2016
This phase I trial studies the side effects and best dose of lenalidomide after donor stem cell transplant and bortezomib in treating patients with high-risk multiple myeloma. Giving low doses of chemotherapy and total-body irradiation before a donor stem cell transplant helps stop the growth of cancer cells. It may also the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving a bortezomib at the time of transplant may stop this from happening. Biological therapies, such as lenalidomide, may stimulate the immune system in different ways and stop cancer cells from growing. Giving lenalidomide after donor stem cell transplant may be an effective treatment for multiple myeloma.

Condition Intervention Phase
Refractory Multiple Myeloma
Stage I Multiple Myeloma
Stage II Multiple Myeloma
Stage III Multiple Myeloma
Drug: fludarabine phosphate
Radiation: total-body irradiation
Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation
Drug: cyclosporine
Drug: mycophenolate mofetil
Drug: bortezomib
Drug: lenalidomide
Other: laboratory biomarker analysis
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Study of Low-dose Lenalidomide After Non-myeloablative Allogeneic Stem Cell Transplant With Bortezomib as GVHD Prophylaxis in High Risk Multiple Myeloma

Resource links provided by NLM:

Further study details as provided by Case Comprehensive Cancer Center:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Safety assessed by evaluating the incidence of toxicity according to CTCAE v. 4.0 [ Time Frame: Up to day 100 ] [ Designated as safety issue: Yes ]
  • Incidence of acute GVHD according to Center for International Blood and Marrow Transplant Research (CIBMTR) [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Incidence of chronic GVHD according to National Institutes of Health (NIH) [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Time to deaths without relapse/recurrence [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: From study entry to death from any cause, assessed at 1 year ] [ Designated as safety issue: No ]

Estimated Enrollment: 12
Study Start Date: October 2013
Estimated Primary Completion Date: September 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

Drug: fludarabine phosphate
Other Names:
  • 2-F-ara-AMP
  • Beneflur
  • Fludara
Radiation: total-body irradiation
Undergo TBI
Other Name: TBI
Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation
Undergo nonmyeloablative allogeneic hematopoietic SCT
Drug: cyclosporine
Given PO
Other Names:
  • ciclosporin
  • cyclosporin
  • cyclosporin A
  • CYSP
  • Sandimmune
Drug: mycophenolate mofetil
Given PO
Other Names:
  • Cellcept
  • MMF
Drug: bortezomib
Given SC
Other Names:
  • LDP 341
  • MLN341
Drug: lenalidomide
Given PO
Other Names:
  • CC-5013
  • IMiD-1
  • Revlimid
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:


I. Identify the maximal tolerated dose (MTD) and safety of lenalidomide up to 10mg following non-myeloablative allogeneic stem cell transplant for multiple myeloma.


I. Assess safety and tolerability of weekly bortezomib following allogeneic hematopoietic stem cell transplant (alloHSCT).

II. Obtain estimates of transplant-related mortality (TRM). 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.


Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

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 such as 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 18-45
  • 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 (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 10-14 days and again within 24 hours prior to prescribing lenalidomide for cycle 1 (prescriptions must be filled within 7 days as required by Revlimid) 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
  • Able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation (patients intolerant to acetylsalicylic acid [ASA] may use warfarin or low molecular weight heparin)

Exclusion Criteria:

  • 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
  • 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
  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: NCT01954784

United States, Ohio
Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center Recruiting
Cleveland, Ohio, United States, 44195
Contact: Hien K. Duong, MD    216-444-2529    duongh@ccf.org   
Principal Investigator: Hien K. Duong         
Sponsors and Collaborators
Case Comprehensive Cancer Center
National Cancer Institute (NCI)
Principal Investigator: Hien Duong, MD Case Comprehensive Cancer Center
  More Information

No publications provided

Responsible Party: Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT01954784     History of Changes
Other Study ID Numbers: CASE1A13  NCI-2013-01777  CASE1A13  P30CA043703 
Study First Received: September 27, 2013
Last Updated: February 9, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Blood Protein Disorders
Cardiovascular Diseases
Hematologic Diseases
Hemorrhagic Disorders
Hemostatic Disorders
Immune System Diseases
Immunoproliferative Disorders
Lymphoproliferative Disorders
Neoplasms by Histologic Type
Vascular Diseases
Fludarabine phosphate
Mycophenolate mofetil
Mycophenolic Acid
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents

ClinicalTrials.gov processed this record on February 11, 2016