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Phase II Study of Fludarabine, Carboplatin, and Topotecan With Thalidomide for Patients With Relapsed/Refractory or High Risk Acute Myelogenous Leukemia, Chronic Myeloid Leukemia and Advanced Myelodysplastic Syndromes


Phase 2
18 Years
N/A
Not Enrolling
Both
Leukemia, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Diseases

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Trial Information

Phase II Study of Fludarabine, Carboplatin, and Topotecan With Thalidomide for Patients With Relapsed/Refractory or High Risk Acute Myelogenous Leukemia, Chronic Myeloid Leukemia and Advanced Myelodysplastic Syndromes


OBJECTIVES:

- Determine the response rate of patients with relapsed/refractory or high-risk acute
myeloid leukemia, chronic myelogenous leukemia, or advanced myelodysplastic syndromes
treated with fludarabine, carboplatin, topotecan, and thalidomide.

- Determine the non-hematologic toxicity profile and time to hematopoietic recovery in
patients treated with this regimen.

- Determine the effects of this regimen on changes in biologic parameters that may
predict response in these patients.

- Correlate bone marrow microvascular density before and after treatment with response in
these patients.

- Determine the prognostic value of pretreatment plasma and serum levels of vascular
endothelial growth factor (VEGF) and/or the modulation of serum levels of VEGF during
treatment in predicting response in these patients.

OUTLINE: Patients are stratified according to diagnosis (previously untreated acute leukemia
vs other).

Patients receive fludarabine IV over 5-10 minutes and carboplatin IV over 24 hours on days
1-5 followed by topotecan IV continuously over 72 hours. Patients receive oral thalidomide
daily beginning within days 1-3 and continuing in the absence of disease progression or
unacceptable toxicity.

Patients with residual disease on day 16-18 may receive a second course of chemotherapy as
above. Patients who achieve remission may receive a third course of chemotherapy as above as
consolidation beginning 4-8 weeks after completion of prior chemotherapy.

Patients are followed monthly for 6 months.

PROJECTED ACCRUAL: A total of 40 patients (20 per stratum) will be accrued for this study.

Inclusion Criteria


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

Type of Study:

Interventional

Study Design:

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Complete response rate

Outcome Time Frame:

6 weeks after treatment

Safety Issue:

No

Principal Investigator

Brenda W. Cooper, MD

Investigator Role:

Study Chair

Investigator Affiliation:

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

Authority:

United States: Federal Government

Study ID:

CWRU1902

NCT ID:

NCT00053287

Start Date:

September 2002

Completion Date:

March 2007

Related Keywords:

  • Leukemia
  • Myelodysplastic Syndromes
  • Myelodysplastic/Myeloproliferative Diseases
  • 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)
  • Leukemia
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive
  • Myelodysplastic Syndromes
  • Preleukemia
  • Myeloproliferative Disorders
  • Myelodysplastic-Myeloproliferative Diseases

Name

Location

Ireland Cancer Center at University Hospitals Case Medical Center, Case Comprehensive Cancer CenterCleveland, Ohio  44106-5065