Fludarabine/Carboplatin/Topotecan w/Thalidomide for Relapsed/Refractory AML, CML and MDS

NCT00053287 | Completed Phase 2 DMC

• 5 other identifiers: CWRU1902P30CA043703CASE-CWRU-1902CELGENE-CWRU-1902CASE-1902
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

Brief Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Thalidomide may stop the growth of cancer cells by stopping blood flow to the tumor. Combining chemotherapy with thalidomide may kill more cancer cells. PURPOSE: Phase II trial to study the effectiveness of combining fludarabine, carboplatin, and topotecan with thalidomide in treating patients who have relapsed or refractory acute myeloid leukemia, chronic myelogenous leukemia, or advanced myelodysplastic syndromes.

Conditions

Leukemia; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Diseases

Keywords

adult acute promyelocytic leukemia (M3); refractory anemia with excess blasts in transformation; refractory anemia with excess blasts; de novo myelodysplastic syndromes; recurrent adult acute myeloid leukemia; secondary acute myeloid leukemia; untreated adult acute myeloid leukemia; blastic phase chronic myelogenous leukemia; relapsing chronic myelogenous leukemia; previously treated myelodysplastic syndromes; secondary myelodysplastic syndromes; atypical chronic myeloid leukemia; myelodysplastic/myeloproliferative disease, unclassifiable; adult acute myeloid leukemia with t(8;21)(q22;q22); adult acute myeloid leukemia with t(16;16)(p13;q22); adult acute myeloid leukemia with inv(16)(p13;q22); adult acute myeloid leukemia with 11q23 (MLL) abnormalities; adult acute myeloid leukemia with t(15;17)(q22;q12)

Outcome Measures

Primary Outcomes (1)

• Complete response rate

  6 weeks after treatment

Interventions

carboplatin DRUG

Carboplatin IV over 24 hours on days 1-5

fludarabine phosphate DRUG

Fludarabine IV over 5-10 minutes on days 1-5.

thalidomide DRUG

Oral thalidomide daily beginning within days 1-3 and continuing in the absence of disease progression or unacceptable toxicity.

topotecan hydrochloride DRUG

Topotecan IV continuously over 72 hours.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: * Diagnosis of 1 of the following: * Acute myeloid leukemia meeting 1 of the following criteria: * Previously untreated and not a candidate for anthracycline-based chemotherapy * In first or second relapse or refractory * Secondary to chemotherapy or an antecedent hematologic disorder and treated with no more than 1 prior intensive induction regimen * Chronic myelogenous leukemia in blast crisis at diagnosis or after prior imatinib mesylate * Myelodysplastic syndromes (MDS) * Refractory anemia with excess blasts (RAEB) or RAEB in transformation * Must meet at least 1 of the following criteria: * Absolute neutrophil count no greater than 500/mm\^3 * Platelet or red cell transfusion-dependent after no more than 1 prior intensive induction chemotherapy * Acute promyelocytic leukemia * t(15, 17) * Failed prior treatment with tretinoin and arsenic * Relapsed disease at least 3 months after prior autologous stem cell transplantation * No active CNS leukemia PATIENT CHARACTERISTICS: Age * 18 and over Performance status * ECOG 0-3 Life expectancy * At least 8 weeks Hematopoietic * See Disease Characteristics Hepatic * Bilirubin no greater than 2.0 mg/dL * AST and ALT less than 3 times upper limit of normal Renal * Creatinine clearance at least 50 mL/min Cardiovascular * Ejection fraction at least 40% * No poorly controlled cardiac disease Pulmonary * No poorly controlled pulmonary disease Other * Not pregnant or nursing * Negative pregnancy test * Fertile female patients must use 1 highly effective and 1 additional method of contraception for 4 weeks before, during, and for at least 4 weeks after study * Male patients must use effective contraception during and for 4 weeks after study * Willing and able to comply with the System for Thalidomide Education and Prescribing Safety (STEPS) program * HIV negative * No poorly controlled infection * No other active malignancy * No severe peripheral neuropathy PRIOR CONCURRENT THERAPY: Biologic therapy * See Disease Characteristics * Prior thalidomide allowed for MDS * At least 5 days since prior hematopoietic growth factors * At least 2 weeks since prior biologic therapy * No prior allogeneic bone marrow transplantation Chemotherapy * See Disease Characteristics * At least 24 hours since prior hydroxyurea Endocrine therapy * At least 24 hours since prior corticosteroids Radiotherapy * Not specified Surgery * Not specified Other * At least 2 weeks since prior cytotoxic anticancer therapy * Prior amifostine allowed for MDS

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Case Comprehensive Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Ireland Cancer Center at University Hospitals Case Medical Center, Case Comprehensive Cancer Center

Cleveland, Ohio, 44106-5065, United States

Location

MeSH Terms

Conditions

Leukemia; Myelodysplastic Syndromes; Myelodysplastic-Myeloproliferative Diseases; Leukemia, Promyelocytic, Acute; Anemia, Refractory, with Excess of Blasts; Leukemia, Myeloid, Acute; Blast Crisis; Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative; Myeloproliferative Disorders; Congenital Abnormalities

Interventions

Carboplatin; fludarabine phosphate; Thalidomide; Topotecan

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases; Leukemia, Myeloid; Anemia, Refractory; Anemia; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Cell Transformation, Neoplastic; Carcinogenesis; Neoplastic Processes; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Camptothecin; Alkaloids

Study Officials

• Brenda W. Cooper, MD

  Ireland Cancer Center at University Hospitals Case Medical Center, Case Comprehensive Cancer Center

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: January 27, 2003
• First Posted: January 28, 2003
• Study Start: September 1, 2002
• Primary Completion: January 1, 2007
• Study Completion: March 1, 2007
• Last Updated: June 10, 2010

Record last verified: 2010-06

Locations

US (1)