Lenalidomide After Donor Stem Cell Transplant and Bortezomib in Treating Patients With High Risk Multiple Myeloma
Refractory Multiple Myeloma - Stage I Multiple Myeloma - Stage II Multiple Myeloma - Stage III Multiple Myeloma
Conditions: official terms
Multiple Myeloma - Neoplasms, Plasma Cell
Study Type
Study Phase
Phase 1
Study Design
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Name: fludarabine phosphate Type: Drug
Name: total-body irradiation Type: Radiation
Name: nonmyeloablative allogeneic hematopoietic stem cell transplantation Type: Procedure
Name: cyclosporine Type: Drug
Name: mycophenolate mofetil Type: Drug
Name: bortezomib Type: Drug
Name: lenalidomide Type: Drug
Name: laboratory biomarker analysis Type: Other
Overall Status
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

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.
Criteria for eligibility
Healthy Volunteers: No
Maximum Age: 65 Years
Minimum Age: 18 Years
Gender: Both
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 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)

- Abnormalities involving chromosome 11

- 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

- 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
Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
Cleveland, Ohio, United States
Status: Recruiting
Contact: Hien K. Duong, MD - 216-444-2529 - duongh@ccf.org
Start Date
October 2013
Case Comprehensive Cancer Center
Case Comprehensive Cancer Center
Record processing date
ClinicalTrials.gov processed this data on July 28, 2015
ClinicalTrials.gov page