Thalidomide in Treating Anemia in Patients With Myelodysplastic Syndrome

A Randomized, Multi-Center, Double-Blind, Placebo-Controlled Trial Assessing The Safety And Efficacy Of Thalidomide (THALOMID) For The Treatment Of Anemia In Red Blood Cell Transfusion-Dependent Patients With Myelodysplastic Syndromes

RATIONALE: Thalidomide may be an effective treatment for anemia caused by myelodysplastic syndrome.

PURPOSE: Randomized phase II trial to study the effectiveness of thalidomide in treating anemia in patients who have myelodysplastic syndrome.

Study Overview

• Status: Completed
• Conditions: Myelodysplastic Syndromes; Leukemia; Myelodysplastic/Myeloproliferative Neoplasms
• Intervention / Treatment: Drug: thalidomide

Detailed Description

OBJECTIVES:

• Determine the efficacy of thalidomide for the treatment of anemia in patients with myelodysplastic syndromes.
• Determine whether this drug reduces the frequency of leukemia transformation and decreases bone marrow blast percentage in these patients.
• Determine the effect of this drug on neutrophil and platelet production and the number of episodes of febrile neutropenia in these patients.
• Determine the safety of this drug in these patients.

OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to International Prognostic Scoring System score (low and intermediate-1 vs intermediate-2 and high) and transfusion dependence (yes vs no). Patients are randomized to one of two treatment arms.

• Arm I: Patients receive oral thalidomide once daily on weeks 1-24.
• Arm II: Patients receive oral placebo once daily on weeks 1-24. In both arms, patients who have not progressed to leukemia after 24 weeks of therapy may receive open-label thalidomide for an additional 24 weeks in the absence of disease progression or unacceptable toxicity.

Patients are followed at 4 weeks.

PROJECTED ACCRUAL: A total of 220 patients (110 per treatment arm) will be accrued for this study.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Wilmington, North Carolina, United States, 28412
      • Ppd Development

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

DISEASE CHARACTERISTICS:

• Diagnosis of myelodysplastic syndromes (MDS) of at least 12 weeks duration

  • Refractory anemia (RA)
  • RA with ringed sideroblasts
  • RA with excess blasts
  • Chronic myelomonocytic
• No therapy-related MDS
• No myelosclerosis or myelofibrosis occupying more than 30% of marrow space (or assessed as grade 3+ or greater)
• No transformation to acute myeloid leukemia
• No more than 20% blasts in bone marrow
• No more than 5% blasts in peripheral blood
• Patients with an erythropoietin level 100 mU/mL or less must have failed epoetin alfa treatment (i.e., at least 30,000 units of epoetin alfa weekly for at least 6 weeks)
• Transfusion-dependent (received at least 2 units of packed RBCs or whole blood within the past 8 weeks) OR
• Transfusion-independent (no packed RBC or whole blood transfusions within the past 8 weeks with 2 hemoglobin levels (at least 7 days apart) less than 11 g/dL)

• No iron deficiency (e.g., absent bone marrow iron store)

  • If marrow aspirate is not evaluable, transferrin saturation must be at least 20% and ferritin at least 50 ng/mL
• No uncorrected B12 or folate deficiency
• No other contributing causes of anemia (e.g., autoimmune or hereditary hemolytic disorders or gastrointestinal blood loss)

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• ECOG 0-2 OR
• Zubrod 0-2

Life expectancy:

• At least 6 months

Hematopoietic:

• See Disease Characteristics
• Absolute neutrophil count at least 500/mm^3

Hepatic:

• Bilirubin no greater than 2.0 mg/dL
• AST and ALT less than 2 times upper limit of normal (ULN)
• Hepatitis B surface antigen negative
• Hepatitis C negative

Renal:

• Creatinine no greater than 1.5 times ULN

Cardiovascular:

• No uncontrolled hypertension
• No clinically significant, symptomatic, unstable cardiovascular disease unrelated to MDS

Pulmonary:

• No clinically significant, symptomatic, unstable pulmonary disease unrelated to MDS

Neurologic:

• No clinically significant, symptomatic, unstable neurologic disease unrelated to MDS
• No history of epilepsy
• No sustained neurologic deficit (e.g., stroke)
• No grade 2 or greater peripheral neuropathy

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use at least 1 highly effective and 1 additional effective method of contraception for 4 weeks prior to, during, and for 4 weeks after study participation
• HIV negative
• No clinically significant, symptomatic, unstable endocrine, gastrointestinal, or genitourinary disease unrelated to MDS
• No other malignancy within the past 5 years except basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
• No life-threatening or active infection requiring parenteral antibiotics
• No other serious concurrent illness

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• See Disease Characteristics
• More than 7 days since prior hematopoietic growth factors (e.g., epoetin alfa, filgrastim (G-CSF), sargramostim (GM-CSF), or interleukin-3)
• No prior thalidomide
• No prior agents intended to inhibit vascular endothelial growth factor or tumor necrosis factor alfa (e.g., etanercept or infliximab)
• No concurrent epoetin alfa

Chemotherapy:

• No concurrent chemotherapy that may be active against MDS

Endocrine therapy:

• More than 30 days since prior androgens
• No requirement for ongoing therapy with systemic corticosteroids

Radiotherapy:

• Not specified

Surgery:

• Not specified

Other:

• More than 30 days since prior treatment for MDS except RBC transfusion or epoetin alfa
• More than 30 days since prior participation in another experimental clinical trial
• More than 30 days since prior experimental drugs
• No other concurrent investigational agents or treatments

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Masking: Double

Collaborators and Investigators

• Sponsor: Roswell Park Cancer Institute
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: James L. Slack, MD, Roswell Park Cancer Institute

Study record dates

Study Major Dates

• Study Start: September 1, 2001
• Primary Completion (Actual): June 1, 2003

Study Registration Dates

• First Submitted: February 14, 2002
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Estimate): January 31, 2013
• Last Update Submitted That Met QC Criteria: January 30, 2013
• Last Verified: January 1, 2013

More Information

Terms related to this study

• Keywords: refractory anemia; refractory anemia with ringed sideroblasts; refractory anemia with excess blasts; chronic myelomonocytic leukemia; de novo myelodysplastic syndromes; previously treated myelodysplastic syndromes; myelodysplastic/myeloproliferative neoplasm, unclassifiable; atypical chronic myeloid leukemia, BCR-ABL1 negative
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Disease; Bone Marrow Diseases; Hematologic Diseases; Precancerous Conditions; Syndrome; Myelodysplastic Syndromes; Leukemia; Preleukemia; Anemia; Myeloproliferative Disorders; Myelodysplastic-Myeloproliferative Diseases; Physiological Effects of Drugs; Anti-Infective Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Anti-Bacterial Agents; Leprostatic Agents; Thalidomide
• Other Study ID Numbers: DS 01-16; RPCI-DS-0116; CELGENE-T-MDS-001; NCI-G01-2044