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

NCT01954784 | Terminated Phase 1 DMC

• 3 other identifiers: CASE1A13NCI-2013-01777P30CA043703
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

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.

Conditions

Refractory Multiple Myeloma; Stage I Multiple Myeloma; Stage II Multiple Myeloma; Stage III Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• 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)

  Day 128 post-transplant

Secondary Outcomes (6)

• Safety assessed by evaluating the incidence of toxicity according to CTCAE v. 4.0

  Up to day 100

• Incidence of acute GVHD according to Center for International Blood and Marrow Transplant Research (CIBMTR)

  1 year

• Incidence of chronic GVHD according to National Institutes of Health (NIH)

  1 year

• Time to deaths without relapse/recurrence

  1 year

• Progression-free survival

  From study entry to progression as defined by international response criteria or death of any cause, whichever comes first, assessed at 1 year

Study Arms (1)

Treatment (nonmyeloablative alloHSCT, lenalidomide)

EXPERIMENTAL

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; Radiation: total-body irradiation; Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation; Drug: cyclosporine; Drug: mycophenolate mofetil; Drug: bortezomib; Drug: lenalidomide; Other: laboratory biomarker analysis

Interventions

fludarabine phosphate DRUG

Also known as: 2-F-ara-AMP, Beneflur, Fludara

Treatment (nonmyeloablative alloHSCT, lenalidomide)

total-body irradiation RADIATION

Undergo TBI

Also known as: TBI

Treatment (nonmyeloablative alloHSCT, lenalidomide)

nonmyeloablative allogeneic hematopoietic stem cell transplantation PROCEDURE

Undergo nonmyeloablative allogeneic hematopoietic SCT

Treatment (nonmyeloablative alloHSCT, lenalidomide)

cyclosporine DRUG

Given PO

Also known as: ciclosporin, cyclosporin, cyclosporin A, CYSP, Sandimmune

Treatment (nonmyeloablative alloHSCT, lenalidomide)

mycophenolate mofetil DRUG

Given PO

Also known as: Cellcept, MMF

Treatment (nonmyeloablative alloHSCT, lenalidomide)

bortezomib DRUG

Given SC

Also known as: LDP 341, MLN341, VELCADE

Treatment (nonmyeloablative alloHSCT, lenalidomide)

lenalidomide DRUG

Given PO

Also known as: CC-5013, IMiD-1, Revlimid

Treatment (nonmyeloablative alloHSCT, lenalidomide)

laboratory biomarker analysis OTHER

Correlative studies

Treatment (nonmyeloablative alloHSCT, lenalidomide)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Case Comprehensive Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

Cleveland, Ohio, 44195, United States

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

fludarabine phosphate; Whole-Body Irradiation; Cyclosporine; Mycophenolic Acid; Bortezomib; Lenalidomide

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Investigative Techniques; Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins; Caproates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids; Lipids; Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Piperidones; Piperidines; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Hien K Liu, MD

  Case Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 27, 2013
• First Posted: October 7, 2013
• Study Start: October 7, 2013
• Primary Completion: January 30, 2017
• Study Completion: January 30, 2017
• Last Updated: February 17, 2017

Record last verified: 2017-02

Locations

US (1)