Clinical trial NCT00053144: Irinotecan and Cytarabine in Treating Patients With Refractory or Recurrent Acute Myeloid Leukemia or Chronic Myelogenous Leukemia
Official title: Irinotecan And Cytarabine In Refractory or Relapsed Acute Myeloid Leukemia And In Chronic Myelogenous Leukemia In Myeloid Blast Transformation: Efficacy And In Vitro Correlates
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Leukemia
Keywords: 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)
Lead sponsor: Roswell Park Cancer Institute
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-01-28
Sex: ALL
Minimum age (years): 15
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug may kill more cancer cells.

PURPOSE: Phase I trial to study the effectiveness of combining irinotecan with cytarabine in treating patients who have refractory or recurrent acute myeloid leukemia or chronic myelogenous leukemia.

Detailed description: 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.

Eligibility 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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
Study officials:
affiliation: Roswell Park Cancer Institute
name: Maria R. Baer, MD
role: STUDY_CHAIR
References: