Lenalidomide in Treating Patients With Progressive or Recurrent Multiple Myeloma After a Donor Stem Cell Transplant

A Phase II Study of Lenalidomide Following Allogeneic Stem Cell Transplant for Multiple Myeloma Patients Who Relapse or Have Disease Progression

This phase II trial studies how well lenalidomide works in treating patients with progressive or recurrent multiple myeloma after a donor stem cell transplant. Lenalidomide may stop the growth of multiple myeloma by blocking blood flow to the cancer. It may also stimulate the immune system in different ways and stop cancer cells from growing.

Study Overview

• Status: Completed
• Conditions: Stage I Multiple Myeloma; Stage II Multiple Myeloma; Stage III Multiple Myeloma; Refractory Multiple Myeloma
• Intervention / Treatment: Drug: lenalidomide

Detailed Description

PRIMARY OBJECTIVES:

I. To evaluate response of relapsed or progressive multiple myeloma to lenalidomide after allogeneic stem cell transplant.

II. Proportion of patients achieving a complete, partial or minor response.

SECONDARY OBJECTIVES:

I. Evaluate toxicity and tolerability of lenalidomide in this setting.

II. For patients with chronic graft-versus-host disease (GVHD), evaluate the response to lenalidomide.

III. Evaluate time to progression (TTP).

IV. Evaluate overall survival (OS).

OUTLINE:

Patients receive lenalidomide orally (PO) on days 1-21. Courses repeat every 28 days for 2 years or longer in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days and then every 3 months thereafter.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Washington
    • Seattle, Washington, United States, 98109
      • Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Understand and voluntarily sign an informed consent form
• Able to adhere to the study visit schedule and other protocol requirements
• Multiple myeloma, having undergone an allogeneic stem cell transplant from a matched or mismatched related or unrelated donor and have relapsed or have disease progression
• Relapse is defined as reappearance of monoclonal protein in serum or urine by immunofixation, new or increased bone lesions or hypercalcemia
• Disease progression is define as a 25% increase in monoclonal protein in serum or a 50% increase in 24 hour urinary monoclonal protein from the lowest level attained at any time point after allogeneic transplant or new or increased bone lesions or hypercalcemia
• All previous cancer therapy, including radiation, hormonal therapy and surgery, must have been discontinued at least 4 weeks prior to treatment in this study, excluding corticosteroids for GVHD
• Eastern Cooperative Oncology Group (ECOG) performance status of =< 2 at study entry
• Absolute neutrophil count >= 1.5 x 10^9/L
• Platelet count >= 50 x 10^9/L
• Serum creatinine =< 2.0 mg/dL
• Total bilirubin =< 1.5 mg/dL
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =< 2 x upper limit of normal (ULN) or =< 5 x ULN if hepatic metastases are present
• Females of childbearing potential (FCBP) must adhere to the scheduled pregnancy testing as required in the Revlimid REMS™ program; FCBP must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 24 hours of prescribing lenalidomide (prescriptions must be filled within 7 days) 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
• Disease free of prior malignancies for >= 5 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix or breast
• Able to take aspirin 81 or 325 mg daily as prophylactic anticoagulation (patients intolerant to acetylsalicylic acid [ASA] may use Coumadin or low molecular weight heparin)
• 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™

Exclusion Criteria:

• Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form
• Pregnant or breast feeding females; (lactating females must agree not to breast feed while taking lenalidomide)
• Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study
• Use of any other experimental drug or therapy within 28 days of baseline
• Known hypersensitivity to thalidomide
• The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs
• Resistance to prior use of lenalidomide
• Concurrent use of other anti-cancer agents or treatments
• Known positive for human immunodeficiency virus (HIV) or infectious hepatitis, type A, B or C
• Acute GVHD grades 3 or 4

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment (lenalidomide); Patients receive lenalidomide PO on days 1-21. Courses repeat every 28 days for 2 years or longer in the absence of disease progression or unacceptable toxicity.	Drug: lenalidomide; Given PO; Other Names: CC-5013; IMiD-1; Revlimid

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response Rate, Defined as the Number of Patients Achieving Complete Response (CR), Partial Response (PR), or Minor Response (MR)	CR: No Monoclonal Protein (MP) in the blood AND no serum/urine MP by Immunofixation (IF < 0) AND < 5% plasma cells in bone marrow aspirate. VGPR: More than 90% decrease of MP and urine M protein < 100 mg/d OR serum protein electrophoresis (SPEP)/urine protein electrophoresis(UPEP) negative but serum immunofixation (IFs) or IFu urine immunofixation (IFu) ) still positive. PR: Over 50% decrease of serum MP AND > 90% reduction in 24h urinary light chain excretion or M proteinuria < 200mg/d MR: Between 25 and 49% decrease of MP in the blood AND 50-89% reduction in 24h urinary light chain excretion (monoclonal proteinuria>200 mg/d)	Up to 9 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events, Graded According to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0	Grade 1-2 adverse events occurring in >10% of participants. Grade 3 or higher adverse events occurring in one or more participants.	Up to 30 days after completion of study treatment
Number of Patients Requiring Dose Interruption, Dose Reduction or Discontinuance of Lenalidomide	Dose interruption, dose reduction or discontinuation of lenalidomide due to toxicity, GVHD or disease progression	Up to 9 years
Number of Patients Who Experience Improvement in GVHD on Lenalidomide, Defined as the Reduction in Severity of GVHD as Defined by the National Institutes of Health (NIH) Consensus Criteria		Up to 9 years
TTP	Time to Progression (TTP): Time from start of therapy to meeting the definition of Progressive Disease (PD). PD: 25% increase compared to the lowest value of: Serum MP (absolute increase at least ≥ 0.5 g/dl); Or: Urine MP (absolute increase at least > 200 mg/24h); Or: for patients without measurable MP, Serum Free Light Chain test: the difference between involved and uninvolved FLC levels (absolute increase at least >100 mg/L)	Up to 9 years
Overall Survival	Kaplan-Meier estimate of survival	At 1 and 2 years after starting treatment with lenalidomide

Collaborators and Investigators

• Sponsor: Fred Hutchinson Cancer Center
• Collaborators: National Cancer Institute (NCI)

Study record dates

Study Major Dates

• Study Start: February 1, 2008
• Primary Completion (Actual): August 1, 2015
• Study Completion (Actual): September 1, 2015

Study Registration Dates

• First Submitted: February 20, 2008
• First Submitted That Met QC Criteria: February 20, 2008
• First Posted (Estimate): February 21, 2008

Study Record Updates

• Last Update Posted (Actual): May 18, 2017
• Last Update Submitted That Met QC Criteria: April 19, 2017
• Last Verified: September 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Physiological Effects of Drugs; Antineoplastic Agents; Immunologic Factors; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Lenalidomide
• Other Study ID Numbers: 2161.00 (Other Identifier: Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium); P30CA015704 (U.S. NIH Grant/Contract); NCI-2009-01592 (Registry Identifier: CTRP (Clinical Trial Reporting Program))