STI571 Plus Combination Chemotherapy in Treating Patients With Chronic Myelogenous Leukemia or Acute Lymphocytic Leukemia

Sponsor

Jonsson Comprehensive Cancer Center (Other)

Overall Status

Completed

CT.gov ID

NCT00015860

Collaborator

National Cancer Institute (NCI) (NIH)

Locations

Duration (Months)

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. STI571 may stop the growth of leukemia cells. Combining chemotherapy and STI571 may kill more cancer cells.

PURPOSE: Phase I/II trial to study the effectiveness of combination chemotherapy plus STI571 in treating patients who have chronic myelogenous leukemia or acute lymphocytic leukemia.

Condition or Disease	Intervention/Treatment	Phase
Leukemia	Drug: daunorubicin hydrochloride Drug: imatinib mesylate Drug: prednisone Drug: vincristine sulfate	Phase 1/Phase 2

Detailed Description

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.

Study Design

Study Type:

Interventional

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

May 1, 2001

Actual Study Completion Date :

Oct 1, 2003

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	City of Hope Comprehensive Cancer Center	Duarte	California	United States	91010
2	Jonsson Comprehensive Cancer Center, UCLA	Los Angeles	California	United States	90095
3	Stanford University Medical Center	Stanford	California	United States	94305-5408
4	Oregon Cancer Institute	Portland	Oregon	United States	97239
5	University of Texas - MD Anderson Cancer Center	Houston	Texas	United States	77030-4009