Thalidomide in Treating Anemia in Patients With Myelodysplastic Syndrome

Leukemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00030550
• Other study ID #: DS 01-16
• Secondary ID: RPCI-DS-0116CELG
• Status: Completed
• Phase: Phase 2
• First received: February 14, 2002
• Last updated: January 30, 2013
• Start date: September 2001

Study information

• Verified date: January 2013
• Source: Roswell Park Cancer Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 0
• Est. primary completion date: June 2003
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leukemia
• Myelodysplastic Syndromes
• Myelodysplastic-Myeloproliferative Diseases
• Myelodysplastic/Myeloproliferative Neoplasms
• Myeloproliferative Disorders
• Preleukemia
• Syndrome

Intervention

Drug:
• thalidomide

Locations

Country	Name	City	State
United States	PPD Development	Wilmington	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Roswell Park Cancer Institute	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States,