Thalidomide in Treating Anemia in Patients With Myelodysplastic Syndrome

Sponsor

Roswell Park Cancer Institute (Other)

Overall Status

Completed

CT.gov ID

NCT00030550

Collaborator

National Cancer Institute (NCI) (NIH)

Location

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Leukemia Myelodysplastic Syndromes Myelodysplastic/Myeloproliferative Neoplasms	Drug: thalidomide	Phase 2

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 Design

Study Type:

Interventional

Allocation:

Randomized

Masking:

Double

Primary Purpose:

Treatment

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

Study Start Date :

Sep 1, 2001

Actual Primary Completion Date :

Jun 1, 2003

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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