search
Back to results

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

Primary Purpose

Refractory Multiple Myeloma, Stage I Multiple Myeloma, Stage II Multiple Myeloma

Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
fludarabine phosphate
total-body irradiation
nonmyeloablative allogeneic hematopoietic stem cell transplantation
cyclosporine
mycophenolate mofetil
bortezomib
lenalidomide
laboratory biomarker analysis
Sponsored by
Case Comprehensive Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Refractory Multiple Myeloma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (nonmyeloablative alloHSCT, lenalidomide)

Arm Description

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.

Outcomes

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)

Secondary Outcome Measures

Safety assessed by evaluating the incidence of toxicity according to CTCAE v. 4.0
Incidence of acute GVHD according to Center for International Blood and Marrow Transplant Research (CIBMTR)
Incidence of chronic GVHD according to National Institutes of Health (NIH)
Time to deaths without relapse/recurrence
Progression-free survival
Overall survival

Full Information

First Posted
September 27, 2013
Last Updated
February 16, 2017
Sponsor
Case Comprehensive Cancer Center
Collaborators
National Cancer Institute (NCI)
search

1. Study Identification

Unique Protocol Identification Number
NCT01954784
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
Study Type
Interventional

2. Study Status

Record Verification Date
February 2017
Overall Recruitment Status
Terminated
Why Stopped
Funding unavailable
Study Start Date
October 7, 2013 (Actual)
Primary Completion Date
January 30, 2017 (Actual)
Study Completion Date
January 30, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Case Comprehensive Cancer Center
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Refractory Multiple Myeloma, Stage I Multiple Myeloma, Stage II Multiple Myeloma, Stage III Multiple Myeloma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
8 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (nonmyeloablative alloHSCT, lenalidomide)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
fludarabine phosphate
Other Intervention Name(s)
2-F-ara-AMP, Beneflur, Fludara
Intervention Type
Radiation
Intervention Name(s)
total-body irradiation
Other Intervention Name(s)
TBI
Intervention Description
Undergo TBI
Intervention Type
Procedure
Intervention Name(s)
nonmyeloablative allogeneic hematopoietic stem cell transplantation
Intervention Description
Undergo nonmyeloablative allogeneic hematopoietic SCT
Intervention Type
Drug
Intervention Name(s)
cyclosporine
Other Intervention Name(s)
ciclosporin, cyclosporin, cyclosporin A, CYSP, Sandimmune
Intervention Description
Given PO
Intervention Type
Drug
Intervention Name(s)
mycophenolate mofetil
Other Intervention Name(s)
Cellcept, MMF
Intervention Description
Given PO
Intervention Type
Drug
Intervention Name(s)
bortezomib
Other Intervention Name(s)
LDP 341, MLN341, VELCADE
Intervention Description
Given SC
Intervention Type
Drug
Intervention Name(s)
lenalidomide
Other Intervention Name(s)
CC-5013, IMiD-1, Revlimid
Intervention Description
Given PO
Intervention Type
Other
Intervention Name(s)
laboratory biomarker analysis
Intervention Description
Correlative studies
Primary Outcome Measure Information:
Title
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
Secondary Outcome Measure Information:
Title
Safety assessed by evaluating the incidence of toxicity according to CTCAE v. 4.0
Time Frame
Up to day 100
Title
Incidence of acute GVHD according to Center for International Blood and Marrow Transplant Research (CIBMTR)
Time Frame
1 year
Title
Incidence of chronic GVHD according to National Institutes of Health (NIH)
Time Frame
1 year
Title
Time to deaths without relapse/recurrence
Time Frame
1 year
Title
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
Title
Overall survival
Time Frame
From study entry to death from any cause, assessed at 1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Hien K Liu, MD
Organizational Affiliation
Case Comprehensive Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

We'll reach out to this number within 24 hrs