Irinotecan And Cytarabine In Refractory or Relapsed Acute Myeloid Leukemia And In Chronic Myelogenous Leukemia In Myeloid Blast Transformation: Efficacy And In Vitro Correlates
15 Years
N/A
Both
Leukemia
Trial Information
Irinotecan And Cytarabine In Refractory or Relapsed Acute Myeloid Leukemia And In Chronic Myelogenous Leukemia In Myeloid Blast Transformation: Efficacy And In Vitro Correlates
OBJECTIVES:
- Determine the activity of irinotecan and cytarabine in patients with refractory or
recurrent acute myeloid leukemia or chronic myelogenous leukemia in myeloid blast
transformation.
- Determine the pharmacokinetics of this regimen in these patients.
- Determine the maximum tolerated dose of irinotecan in this regimen in these patients.
- Correlate the clinical activity of this drug with cellular endpoints associated with
DNA synthesis inhibition, DNA repair, induction of apoptosis, and drug resistance in
these patients.
OUTLINE: This is a dose-escalation study of irinotecan.
Patients receive irinotecan IV over 90 minutes and cytarabine IV over 60 minutes on days
1-6. Courses repeat every 4 weeks in the absence of disease progression or unacceptable
toxicity.
Cohorts of 3-6 patients receive escalating doses of irinotecan until the maximum tolerated
dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2
of 6 patients experience dose-limiting toxicity. An additional 9 patients with
refractory/relapsed acute myeloid leukemia and 9 patients with chronic myelogenous leukemia
in myeloid blast transformation are treated at the MTD.
Patients are followed for survival.
PROJECTED ACCRUAL: A total of 3-36 patients will be accrued for this study within 2.5 years.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Histologically confirmed acute myeloid leukemia (M0-M7)
- De novo or secondary disease
- Previously treated and refractory to prior therapy (which has included
high-dose cytarabine and an anthracycline)
- Antecedent hematologic disorders allowed OR
- Histologically confirmed Philadelphia chromosome-positive chronic myelogenous
leukemia in myeloid blast transformation
- Treated or untreated
- Blast transformation defined by at least 20% blasts in marrow and/or blood
- Myeloid lineage defined by immunophenotyping
PATIENT CHARACTERISTICS:
Age
- 15 and over
Performance status
- 0-3
Life expectancy
- At least 4 weeks
Hematopoietic
- See Disease Characteristics
Hepatic
- Bilirubin less than 2 times upper limit of normal (ULN)
- SGOT less than 2 times ULN
Renal
- Creatinine less than 1.5 times ULN
Other
- Not pregnant or nursing
- Negative pregnancy test
- No other concurrent serious medical or psychiatric illness that would preclude study
consent
PRIOR CONCURRENT THERAPY:
Biologic therapy
- Not specified
Chemotherapy
- See Disease Characteristics
- Prior chemotherapy for an antecedent malignancy or other medical condition allowed
Endocrine therapy
- Not specified
Radiotherapy
- Prior radiotherapy for an antecedent malignancy or other medical condition allowed
Surgery
- Not specified
Type of Study:
Interventional
Study Design:
Primary Purpose: Treatment
Principal Investigator
Maria R. Baer, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Roswell Park Cancer Institute
Authority:
United States: Food and Drug Administration
Study ID:
CDR0000269286
NCT ID:
NCT00053144
Start Date:
November 1999
Completion Date:
March 2003
Related Keywords:
- Leukemia
- recurrent adult acute myeloid leukemia
- Philadelphia chromosome positive chronic myelogenous leukemia
- secondary acute myeloid leukemia
- blastic phase chronic myelogenous leukemia
- relapsing chronic myelogenous leukemia
- adult acute monocytic leukemia (M5b)
- adult acute erythroid leukemia (M6)
- adult acute megakaryoblastic leukemia (M7)
- adult acute minimally differentiated myeloid leukemia (M0)
- adult acute myeloblastic leukemia with maturation (M2)
- adult acute myeloblastic leukemia without maturation (M1)
- adult acute myelomonocytic leukemia (M4)
- adult acute monoblastic leukemia (M5a)
- adult acute promyelocytic leukemia (M3)
- Leukemia
- Leukemia, Myeloid, Acute
- Leukemia, Myeloid
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Name | Location |
|---|---|
| Roswell Park Cancer Institute | Buffalo, New York 14263 |
