Clinical Trials /

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

NCT01954784

Description:

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.

Related Conditions:
  • Multiple Myeloma
Recruiting Status:

Terminated

Phase:

Phase 1

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: CASE1A13
  • SECONDARY ID: NCI-2013-01777
  • SECONDARY ID: CASE1A13
  • SECONDARY ID: P30CA043703
  • NCT ID: NCT01954784

Conditions

  • Refractory Multiple Myeloma
  • Stage I Multiple Myeloma
  • Stage II Multiple Myeloma
  • Stage III Multiple Myeloma

Interventions

DrugSynonymsArms
fludarabine phosphate2-F-ara-AMP, Beneflur, FludaraTreatment (nonmyeloablative alloHSCT, lenalidomide)
cyclosporineciclosporin, cyclosporin, cyclosporin A, CYSP, SandimmuneTreatment (nonmyeloablative alloHSCT, lenalidomide)
mycophenolate mofetilCellcept, MMFTreatment (nonmyeloablative alloHSCT, lenalidomide)
bortezomibLDP 341, MLN341, VELCADETreatment (nonmyeloablative alloHSCT, lenalidomide)
lenalidomideCC-5013, IMiD-1, RevlimidTreatment (nonmyeloablative alloHSCT, lenalidomide)

Purpose

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.

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.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (nonmyeloablative alloHSCT, lenalidomide)ExperimentalPREPARATIVE 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.
  • fludarabine phosphate
  • cyclosporine
  • mycophenolate mofetil
  • bortezomib
  • lenalidomide

Eligibility Criteria

        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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Safety assessed by evaluating the incidence of toxicity according to CTCAE v. 4.0
Time Frame:Up to day 100
Safety Issue:
Description:
Measure:Incidence of acute GVHD according to Center for International Blood and Marrow Transplant Research (CIBMTR)
Time Frame:1 year
Safety Issue:
Description:
Measure:Incidence of chronic GVHD according to National Institutes of Health (NIH)
Time Frame:1 year
Safety Issue:
Description:
Measure:Time to deaths without relapse/recurrence
Time Frame:1 year
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure:Overall survival
Time Frame:From study entry to death from any cause, assessed at 1 year
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Terminated
Lead Sponsor:Case Comprehensive Cancer Center

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