A Phase I/II Trial of STI-571 and Chemotherapy in Lymphoid Blast Crisis of Chronic Myeloid Leukemia and Philadelphia Chromosome-Positive Acute Lymphoid Leukemia
18 Years
N/A
Both
Leukemia
Trial Information
A Phase I/II Trial of STI-571 and Chemotherapy in Lymphoid Blast Crisis of Chronic Myeloid Leukemia and Philadelphia Chromosome-Positive Acute Lymphoid Leukemia
OBJECTIVES:
- Determine the maximum tolerated dose of daunorubicin when combined with imatinib
mesylate, vincristine, and prednisone in patients with lymphoid blastic phase chronic
myelogenous leukemia or Philadelphia chromosome-positive acute lymphoblastic leukemia.
- Determine the safety of this regimen in these patients.
- Determine the pharmacokinetics of this regimen in these patients.
- Determine the frequency of hematologic and cytogenetic responses in patients treated
with this regimen.
- Determine the duration of response of this patient population treated with this
regimen.
- Determine the survival of patients treated with this regimen.
OUTLINE: This is a multicenter, dose-escalation study of daunorubicin.
Patients who have not previously received imatinib mesylate receive oral imatinib mesylate
on days 1-35. Patients who have previously received imatinib mesylate for at least 28 days
receive oral imatinib mesylate on days 22-35. All patients receive daunorubicin IV over 2-3
minutes on days 1-3, vincristine IV over 1 minute on days 1, 8, 15, and 22, and oral
prednisone on days 1-28. Patients with more than 5% residual blasts in bone marrow on day 28
receive a second course in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of daunorubicin until the maximum tolerated
dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6
patients experience dose-limiting toxicity. Once the MTD is determined, additional patients
are treated at the recommended phase II dose.
PROJECTED ACCRUAL: A maximum of 46 patients will be accrued for this study.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- One of the following diagnoses:
- Chronic myelogenous leukemia in lymphoid blast crisis
- Acute lymphoblastic leukemia (ALL) that is in first relapse or failed induction
- No more than 1 prior course of induction chemotherapy
- Philadelphia chromosome-positive (Ph+) by cytogenetic analysis OR bcr/abl
translocation by fluorescent in situ hybridization
- At least 30% blasts in bone marrow
- Ineligible for or refused allogeneic stem cell transplantation
- Not previously treated with imatinib mesylate OR currently receiving imatinib
mesylate with stable disease on 2 bone marrow biopsies at least 2 weeks apart
PATIENT CHARACTERISTICS:
Age:
- 18 and over
Performance status:
- ECOG 0-2
Life expectancy:
- Not specified
Hematopoietic:
- See Disease Characteristics
Hepatic:
- Bilirubin less than 3 times upper limit of normal (ULN)
- ALT and AST less than 3 times ULN
Renal:
- Creatinine less than 2 times ULN
Cardiovascular:
- No New York Heart Association class III or IV cardiac disease
Other:
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective barrier contraception during and for at least 2
weeks after study for female patients and at least 3 months after study for male
patients
PRIOR CONCURRENT THERAPY:
Biologic therapy:
- See Disease Characteristics
- No prior allogeneic bone marrow or peripheral blood stem cell transplantation
- At least 48 hours since prior interferon alfa
Chemotherapy:
- See Disease Characteristics
- At least 24 hours since prior hydroxyurea
- At least 6 weeks since prior busulfan
- Concurrent hydroxyurea or anagrelide for severe leukocytosis or thrombocytosis
allowed
Endocrine therapy:
- Not specified
Radiotherapy:
- Not specified
Surgery:
- Not specified
Other:
- No prior therapy for blast crisis except hydroxyurea
- No prior salvage or reinduction therapy for Ph+ ALL
- At least 4 weeks since other prior investigational agents
Type of Study:
Interventional
Study Design:
Primary Purpose: Treatment
Principal Investigator
Ronald Paquette, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Jonsson Comprehensive Cancer Center
Authority:
United States: Federal Government
Study ID:
CDR0000068444
NCT ID:
NCT00015860
Start Date:
May 2001
Completion Date:
October 2003
Related Keywords:
- Leukemia
- recurrent adult acute lymphoblastic leukemia
- relapsing chronic myelogenous leukemia
- blastic phase chronic myelogenous leukemia
- Leukemia
- Leukemia, Lymphoid
- Precursor Cell Lymphoblastic Leukemia-Lymphoma
- Leukemia, Myeloid
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive
- Philadelphia Chromosome
Name | Location |
|---|---|
| University of Texas - MD Anderson Cancer Center | Houston, Texas 77030-4009 |
| Jonsson Comprehensive Cancer Center, UCLA | Los Angeles, California 90095-1781 |
| Stanford University Medical Center | Stanford, California 94305-5408 |
| City of Hope Comprehensive Cancer Center | Duarte, California 91010 |
| Oregon Cancer Institute | Portland, Oregon 97201-3098 |
