Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

Trial Description

Summary

This randomized phase III trial is studying lenalidomide to see how well it works with or without epoetin alfa in treating patients with myelodysplastic syndrome and anemia. Lenalidomide may stop the growth of myelodysplastic syndrome by blocking blood flow to the cell. Colony stimulating factors, such as epoetin alfa, may increase the number of immune cells found in bone marrow or peripheral blood. It is not yet known whether lenalidomide is more effective with or without epoetin alfa in treating patients with myelodysplastic syndrome and anemia

Further Study Information

PRIMARY OBJECTIVES:

I. To compare the rate of major erythroid response (MER) in patients with low- or intermediate-1-risk myelodysplastic syndromes treated with lenalidomide with vs without epoetin alfa.

SECONDARY OBJECTIVES:

I. To compare the time to MER in patients treated with these regimens. II. To evaluate the duration of MER in patients treated with these regimens. III. To estimate the frequency of MER to salvage combination chemotherapy in patients who fail to experience an MER after treatment with lenalidomide alone.

IV. To evaluate and compare the frequency of minor erythroid response in patients treated with these regimens.

V. To investigate the mechanism and target of lenalidomide action in patients with chromosome 5q31.1 deletion.

VI. To evaluate the frequency of cytogenetic response and progression, and the relationship between cytogenetic pattern and erythroid response.

VII. To evaluate the frequency of bone marrow response (complete response and partial response) in patients treated with these regimens.

OUTLINE: This is a multicenter study. Patients are stratified according to erythropoietin level (≤ 500 mU/mL vs > 500 mU/mL) and prior erythropoietic growth factor (yes vs no). Patients are randomized to 1 of 2 treatment arms. Patients with del 5q31.1 karyotype are assigned to treatment arm I.

ARM I: Patients receive oral lenalidomide once daily on days 1-21.

ARM II: Patients receive oral lenalidomide once daily on days 1-21 and epoetin alfa subcutaneously once weekly.

In both arms, treatment repeats every 28 days for 4 courses. Patients who achieve a major erythroid response (MER) may continue treatment beyond 4 courses in the absence of disease progression, disease conversion to acute myeloid leukemia, or unacceptable toxicity. Patients in arm I who fail to achieve MER or who achieve MER but relapse after 16 weeks of treatment with lenalidomide may crossover and receive treatment in arm II.

After completion of study treatment, patients are followed for 6 months.

Eligibility Criteria

Inclusion Criteria:

• Documented diagnosis of 1 of the following:

• Myelodysplastic syndromes (MDS) lasting ≥ 3 months according to WHO criteria

• Disease must not be secondary to treatment with radiotherapy, chemotherapy, and/or immunotherapy for malignant or autoimmune diseases

• Non-proliferative chronic myelomonocytic leukemia (WBC < 12,000/mm³)

• International prognostic scoring system (IPSS) category of low- or intermediate-1-risk MDS as determined by cytogenetic analysis

• Cytogenetic analysis required if current bone marrow biopsy is a dry tap

• Patients with cytogenetic failure and < 10% marrow blasts are eligible

• Patients with cytogenetic failure must have prior cytogenetic results (FISH is nota substitute) within 6 months after completion of the last type of MDS treatment (in this case, growth factors are not considered a type of MDS treatment).

• Must have symptomatic anemia with hemoglobin < 9.5 g/dL* (transfusion-independent or RBC transfusion-dependent [i.e., ≥ 2 units/month]) within the past 8 weeks

• For patients without the deletion 5q 31.1, must have failed treatment with an erythropoietic growth factor OR have a low probability of response to rhu-erythropoietin, as defined by the following:

• Prior erythropoietin failure: requires ≥ 40,000 units epoetin alfa/week for 8 weeks or equivalent dose of darbepoetin alfa for 8 weeks and failed to achieve transfusion independence (in transfusion-dependent patients) or failed to achieve ≥ 2 g rise in hemoglobin sustained for ≥4 weeks (in transfusion-independent patients)

• Low erythropoietin response profile: rhu-erythropoietin and epoetin alfa-naive patients receiving ≥ 2 U pRBC/month for ≥ 8 weeks and serum erythropoietin ≥ 500 mU/mL in the 8 weeks prior to study randomization for a hemoglobin < 9.5 g/dL

• ANC ≥ 500/mm^3 (myeloid growth factor support independent)

• Platelet count ≥ 50,000/mm^3 (platelet transfusion independent)

• Serum creatinine ≤ 1.5 times upper limit of normal (ULN)

• Creatinine clearance ≥ 30 mL/min

• AST and ALT ≤ 2.0 times ULN

• Serum total bilirubin < 3.0 mg/dL

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective double-method contraception for ≥ 4 weeks before, during, and for 4 weeks after completion of study treatment

• No uncontrolled seizures or uncontrolled hypertension

• No history of other malignancy (except basal cell or squamous cell skin carcinoma or carcinoma in situ of the cervix or breast) unless the patient has been confirmed disease-free for ≥ 3 years

• No serious medical condition or any other unstable medical comorbidity, or psychiatric illness that would preclude informed consent or put the patient at unacceptable risk during study treatment

• No thromboembolic events within the past 3 years

• No known allergic reaction to epoetin alfa (Procrit®) or human serum albumin

• No prior desquamating (blistering) rash from thalidomide

• No prior allergic reactions to thalidomide ≥ grade 3

• No known HIV-1 seropositivity

• No documented iron deficiency

• Must have documented bone marrow iron stores (if marrow iron stain is not available, transferrin saturation must be > 20% or serum ferritin > 100 ng/mL)

• No clinically significant anemia resulting from iron, B_12, or folate deficiencies, autoimmune or hereditary hemolysis, or gastrointestinal bleeding

• Concurrent steroids for adrenal failure, hormones for noncancer-related conditions (e.g., insulin for diabetes), or intermittent dexamethasone as an antiemetic allowed

• No prior lenalidomide

• Prior thalidomide allowed

• More than 8 weeks since prior cytotoxic chemotherapeutic agents or experimental agents (agents that are not commercially available) for the treatment of MDS

• At least 28 days since prior non-transfusion therapy, including all types of growth factors, for MDS

• Concurrent prophylactic hydrocortisone to prevent transfusion reaction allowed

Trial Contact Information

Trial Lead Organizations/Sponsors

National Cancer Institute

Alan List

Principal Investigator

U.S.A.
Alabama
	Birmingham
	UAB Comprehensive Cancer Center
		Carla I. Falkson	Ph: 205-934-0309
California
	Los Angeles
	Kaiser Permanente Medical Center - Los Angeles
		Han A Koh	Ph: 626-564-3455
	San Diego
	Kaiser Permanente - Mission
		Han A Koh	Ph: 626-564-3455
	Stanford
	Stanford Cancer Center
		Peter L. Greenberg	Ph: 650-498-7061
			Email: ccto-office@stanford.edu
Florida
	Hollywood
	Joe DiMaggio Children's Hospital
		Daren D Grosman	Ph: 888-823-5923
			Email: ctsucontact@westat.com
	Leesburg
	Leesburg Regional Medical Center
		Pablo C Reyes
			Email: info@cfhalliance.org
Illinois
	Joliet
	Joliet Oncology-Hematology Associates, Limited - West
		Kulumani M Sivarajan	Ph: 815-730-3098
			Email: maureenc@jolietoncology.com
	Springfield
	Regional Cancer Center at Memorial Medical Center
		James L. Wade	Ph: 217-876-4740
			Email: kcheek@dmhhs.org
Indiana
	Beech Grove
	St. Francis Hospital and Health Centers - Beech Grove Campus
		Howard M. Gross	Ph: 765-983-3000
	Fort Wayne
	Fort Wayne Medical Oncology and Hematology
		Sreenivasa Rao Nattam	Ph: 260-484-8830
			Email: ledgar@fwmoh.com
Michigan
	Ann Arbor
	University of Michigan Comprehensive Cancer Center
		Dale L Bixby	Ph: 800-865-1125
	Flint
	Genesys Hurley Cancer Institute
		Philip J. Stella	Ph: 734-712-3456
	Marquette
	Upper Michigan Cancer Center at Marquette General Hospital
		Amy Weise	Ph: 313-576-9363
Mississippi
	Kessler AFB
	Keesler Air Force Base Medical Center
		Louis M Varner	Ph: 800-700-8603
North Dakota
	Bismarck
	Bismarck Cancer Center
		John T Reynolds	Ph: 701-323-5760
			Email: tfischer@mohs.org
Pennsylvania
	Bryn Mawr
	Bryn Mawr Hospital
		Paul B. Gilman	Ph: 484-476-2649
			Email: wellenbachj@mlhs.org
	Paoli
	Cancer Center of Paoli Memorial Hospital
		Paul B. Gilman	Ph: 484-476-2649
			Email: wellenbachj@mlhs.org
	Phoenixville
	Cancer Center at Phoenixville Hospital
		Carl W. Sharer	Ph: 610-983-1908
	Wynnewood
	CCOP - Main Line Health
		Paul B. Gilman	Ph: 484-476-2649
			Email: wellenbachj@mlhs.org
	Lankenau Cancer Center at Lankenau Hospital
		Paul B. Gilman	Ph: 484-476-2649
			Email: wellenbachj@mlhs.org
South Dakota
	Sioux Falls
	Avera Cancer Institute
		Addison R Tolentino	Ph: 800-657-4377
			Email: Jan.Healy@avera.org
Virginia
	Charlottesville
	University of Virginia Cancer Center
		Michael Eugene Williams	Ph: 434-243-6143
Wisconsin
	Appleton
	Fox Valley Hematology and Oncology - East Grant Street
		Timothy F Goggins	Ph: 920-749-1171
	Eau Claire
	Marshfield Clinic Cancer Care at Regional Cancer Center
		Bilal H Naqvi	Ph: 800-839-3956
	Marshfield
	Marshfield Clinic - Marshfield Center
		Bilal H Naqvi	Ph: 800-839-3956
	Saint Joseph's Hospital
		Bilal H Naqvi	Ph: 800-839-3956
	Minocqua
	Marshfield Clinic - Lakeland Center
		Bilal H Naqvi	Ph: 800-839-3956
	Rhinelander
	Ministry Medical Group at Saint Mary's Hospital
		Bilal H Naqvi	Ph: 800-839-3956
	Rice Lake
	Marshfield Clinic - Indianhead Center
		Bilal H Naqvi	Ph: 800-839-3956
	Stevens Point
	Marshfield Clinic at Saint Michael's Hospital
		Bilal H Naqvi	Ph: 800-839-3956
	Weston
	Marshfield Clinic - Weston Center
		Bilal H Naqvi	Ph: 800-839-3956
	Wisconsin Rapids
	Marshfield Clinic - Wisconsin Rapids Center
		Bilal H Naqvi	Ph: 800-839-3956

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00843882
Information obtained from ClinicalTrials.gov on April 11, 2013

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