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Thalidomide in Treating Anemia in Patients With Myelodysplastic Syndrome

Primary Purpose

Leukemia, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Neoplasms

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
thalidomide
Sponsored by
Roswell Park Cancer Institute
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Leukemia focused on measuring refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess blasts, de novo myelodysplastic syndromes, chronic myelomonocytic leukemia, previously treated myelodysplastic syndromes, myelodysplastic/myeloproliferative neoplasm, unclassifiable, atypical chronic myeloid leukemia, BCR-ABL1 negative

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

  • PPD Development

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
February 14, 2002
Last Updated
January 30, 2013
Sponsor
Roswell Park Cancer Institute
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00030550
Brief Title
Thalidomide in Treating Anemia in Patients With Myelodysplastic Syndrome
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 Type
Interventional

2. Study Status

Record Verification Date
January 2013
Overall Recruitment Status
Completed
Study Start Date
September 2001 (undefined)
Primary Completion Date
June 2003 (Actual)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Name of the Sponsor
Roswell Park Cancer Institute
Collaborators
National Cancer Institute (NCI)

4. Oversight

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Leukemia, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Neoplasms
Keywords
refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess blasts, de novo myelodysplastic syndromes, chronic myelomonocytic leukemia, previously treated myelodysplastic syndromes, myelodysplastic/myeloproliferative neoplasm, unclassifiable, atypical chronic myeloid leukemia, BCR-ABL1 negative

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Masking
Double
Allocation
Randomized

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
thalidomide

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
James L. Slack, MD
Organizational Affiliation
Roswell Park Cancer Institute
Official's Role
Study Chair
Facility Information:
Facility Name
PPD Development
City
Wilmington
State/Province
North Carolina
ZIP/Postal Code
28412
Country
United States

12. IPD Sharing Statement

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Thalidomide in Treating Anemia in Patients With Myelodysplastic Syndrome

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