Thalidomide in Treating Patients With Myelodysplastic Syndrome

Phase II Study of Thalidomide in the Treatment of Myelodysplastic Syndromes in Adults: A Clinical and Biologic Study

Phase II trial to study the effectiveness of thalidomide in treating patients who have myelodysplastic syndrome. Thalidomide may improve the immune system's ability to fight myelodysplastic syndrome

Study Overview

• Status: Completed
• Conditions: Chronic Myelomonocytic Leukemia; Previously Treated Myelodysplastic Syndromes; Secondary Myelodysplastic Syndromes; de Novo Myelodysplastic Syndromes; Refractory Anemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Refractory Anemia With Ringed Sideroblasts
• Intervention / Treatment: Other: laboratory biomarker analysis; Drug: thalidomide

Detailed Description

OBJECTIVES:

I. Determine whether thalidomide improves cytopenias in patients with myelodysplastic syndromes.

II. Determine the toxicity of this regimen in these patients. III. Determine whether this regimen down regulates the peripheral blood levels of tumor necrosis factor alpha, interferon gamma, and interleukin-12 and whether these changes correlate with clinical response in these patients.

IV. Determine whether this regimen alters the peripheral blood T-cell subset distribution and whether these changes correlate with clinical response in these patients.

V. Determine the effect of this regimen on bone marrow microvessel density and whether these effects correlate with clinical response in these patients.

OUTLINE: This is a multicenter study. Patients are stratified according to prognosis (favorable vs unfavorable). (Favorable stratum closed to accrual 12/28/01)

Patients receive oral thalidomide once daily. Treatment continues for 5 years in the absence of disease progression or unacceptable toxicity.

Patients are followed every 6 months for 1 year and then annually for 4 years.

PROJECTED ACCRUAL: A total of 20-58 patients (10-29 per stratum) will be accrued for this study within 20 months. (Favorable stratum closed to accrual 12/28/01)

• Study Type: Interventional
• Enrollment (Actual): 29
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • North Central Cancer Treatment Group

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

Inclusion Criteria:

• Pre-transfusion hemoglobin =< 10 g/dL
• Pre-transfusion platelet count =< 50,000/μL
• Absolute neutrophil count < 1000/μL
• Total bilirubin ≤ 1.5 x UNL
• Alkaline phosphatase ≤ 3 x UNL
• AST ≤ 3 x UNL
• Creatinine ≤ 1.5 x UNL

• A diagnosis of MDS as demonstrated in the bone marrow; any subtypes are eligible including:

  • Refractory anemia (cytopenia)
  • Refractory anemia with ringed sideroblasts
  • Chronic myelomonocytic leukemia
  • Refractory anemia with excess blasts
  • Refractory anemia with excess blasts in transformation
  • Unclassified MDS
• Patients with refractory anemia with excess blasts in transformation who are not candidates for (or who decline) induction chemotherapy are eligible; those patients who were candidates for (and accepted) induction chemotherapy should have failed at least 1 chemotherapy regimen prior to entry
• Patients who are candidates for marrow transplantation should have this option discussed prior to study entry

Exclusion Criteria:

• Any of the following as this regimen may be harmful to a developing fetus or nursing child:

  • Pregnant women
  • Nursing women
  • Women of childbearing potential or their sexual partners who are unwilling to employ 2 adequate methods of contraception (condoms, diaphragm, birth control pills, injections, intrauterine device [IUD], surgical sterilization, subcutaneous implants, or abstinence, etc.)
• Peripheral neuropathy (by history or clinical exam)
• Concomitant therapy ≤ 30 days for myelodysplastic syndrome with any specific agent including chemotherapy, corticosteroids and/or growth factors (i.e. erythropoietin, G-CSF, GM-CSF, thrombopoietic agent); patients on chronic low-dose corticosteriods (< 20 mg/d) for reasons other than MDS are allowed
• Uncontrolled infections

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment (thalidomide); Patients receive oral thalidomide once daily. Treatment continues for 5 years in the absence of disease progression or unacceptable toxicity.	Other: laboratory biomarker analysis; Correlative studies; Drug: thalidomide; Given orally; Other Names: Kevadon; Synovir; THAL; Thalomid

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Confirmed response defined as complete hematologic response (CHR) or partial response (PR) or hematological improvement (HI) on 2 consecutive evaluations in terms of proportion of successes measured using criteria reported by Cheson et al	Ninety-five percent confidence intervals for the true success proportion will be calculated according to the approach of Duffy and Santner.	Up to 3 months
Incidence and severity of toxicities, graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) v2.0		Up to 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Survival time	Estimated using the method of Kaplan-Meier.	Time from registration to death due to any cause, assessed up to 5 years
Time to disease progression	Estimated using the method of Kaplan-Meier.	Time from registration to documentation of disease progression, assessed up to 5 years
Duration of response measured using criteria reported by Cheson et al		Date at which the patient's objective status is first noted to be either a CHR or PR to the date progression is documented, assessed up to 5 years
Time to treatment failure		Time from the date of registration to the date at which the patient is removed from treatment due to progression, toxicity, or refusal, assessed up to 5 years

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Alvaro Moreno Aspitia, North Central Cancer Treatment Group

Study record dates

Study Major Dates

• Study Start: April 1, 2001
• Primary Completion (Actual): February 1, 2007

Study Registration Dates

• First Submitted: May 6, 2001
• First Submitted That Met QC Criteria: February 26, 2004
• First Posted (Estimate): February 27, 2004

Study Record Updates

• Last Update Posted (Estimate): January 24, 2013
• Last Update Submitted That Met QC Criteria: January 23, 2013
• Last Verified: January 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Disease; Bone Marrow Diseases; Hematologic Diseases; Precancerous Conditions; Myelodysplastic-Myeloproliferative Diseases; Leukemia; Leukemia, Myeloid; Syndrome; Myelodysplastic Syndromes; Preleukemia; Leukemia, Myelomonocytic, Chronic; Leukemia, Myelomonocytic, Juvenile; Anemia; Anemia, Refractory, with Excess of Blasts; Anemia, Refractory; 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: NCI-2012-01856; U10CA025224 (U.S. NIH Grant/Contract); N998B; CDR0000068580 (Registry Identifier: PDQ (Physician Data Query))