A Phase I/II Dose-Finding Study to Determine the Safety, Tolerability, and Anti-Leukemic Effects of STI571 (NSC 716051) in Combination With Interferon-alpha in Patients With Chronic Myelogenous Leukemia in Chronic Phase


Phase 2
18 Years
N/A
Not Enrolling
Both
Leukemia

Thank you

Trial Information

A Phase I/II Dose-Finding Study to Determine the Safety, Tolerability, and Anti-Leukemic Effects of STI571 (NSC 716051) in Combination With Interferon-alpha in Patients With Chronic Myelogenous Leukemia in Chronic Phase


OBJECTIVES:

- Determine the maximum tolerated dose of interferon alfa administered with imatinib
mesylate in patients with chronic phase chronic myelogenous leukemia. (Phase I closed
to accrual as of 7/9/03.)

- Determine the safety and tolerability of this regimen in this patient population.

- Determine the complete, major, and minor cytogenetic response rates and complete
hematologic response rate in patients after 6 and 12 months of treatment with this
regimen.

- Determine the molecular response (reverse transcriptase-polymerase chain reaction for
bcr-abl) rate in patients who have a complete cytogenetic response after 6 and 12
months of treatment with this regimen.

- Determine the pharmacokinetics of this regimen in these patients.

OUTLINE: This is a dose-escalation, multicenter study.

- Phase I (closed to accrual as of 7/9/03): Patients receive oral imatinib mesylate once
daily beginning on day 1 and interferon alfa (IFN-A) subcutaneously once daily or 3
times weekly beginning on day 14. Courses repeat every 35 days for up to 1 year in the
absence of disease progression or unacceptable toxicity. After completion of 1 year of
therapy, patients may receive additional therapy, provided that the patient is
benefiting from imatinib mesylate. IFN-A is discontinued in patients who achieve a
molecular remission that is confirmed on 2 successive bone marrow samples. Imatinib
mesylate is discontinued in patients who achieve and maintain a molecular remission for
2 years.

Sequential dose escalation of IFN-A is followed by sequential dose escalation of imatinib
mesylate. Cohorts of 3-6 patients receive escalating doses of IFN-A and then imatinib
mesylate until the maximum tolerated dose (MTD) of the combination is determined. The MTD is
defined as the dose preceding that at which 2 of 6 patients experience dose-limiting
toxicity.

- Phase II: Patients receive imatinib mesylate and IFN-A as in phase I at the established
MTD.

Patients are followed for 30 days.

PROJECTED ACCRUAL: Approximately 3-15 patients will be accrued for the phase I portion of
this study. (Phase I closed to accrual as of 7/9/03.) A total of 40 patients will be accrued
for the phase II portion of the study within 3-4 months.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Cytogenetically confirmed chronic myelogenous leukemia (CML)

- Less than 15% blasts in peripheral blood or bone marrow

- Less than 30% blasts and promyelocytes in peripheral blood or bone marrow

- Less than 20% basophils in blood or bone marrow

- Platelet count at least 100,000/mm^3

- No leukemia beyond bone marrow, blood, liver, or spleen

- No chloroma

- Phase I (closed to accrual as of 7/9/03):

- Philadelphia (Ph) chromosome-positive CML in chronic phase

- Phase II:

- Newly diagnosed Ph chromosome-positive CML in chronic phase

- Initial diagnosis within 6 months of study

- No prior therapy for CML except hydroxyurea and/or anagrelide hydrochloride

- Phase I (closed to accrual as of 7/9/03) and II:

- No identified sibling donors where allogeneic stem cell transplantation is
elected as first-line therapy

PATIENT CHARACTERISTICS:

Age:

- 18 and over

Performance status:

- ECOG 0-2

Life expectancy:

- Not specified

Hematopoietic:

- See Disease Characteristics

Hepatic:

- Bilirubin no greater than 1.5 times upper limit of normal (ULN)

- AST or ALT no greater than 2 times ULN

Renal:

- Creatinine no greater than 1.5 times ULN

Cardiovascular:

- No New York Heart Association class III or IV heart disease

Other:

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use 2 methods of effective barrier contraception during and for
at least 3 months after study participation

- No other serious uncontrolled medical condition

- No autoimmune disease

- No prior noncompliance to medical regimens or potential unreliability

- No prior grade 3 or greater non-hematologic toxicity due to prior interferon (phase I
[closed to accrual as of 7/9/03])

PRIOR CONCURRENT THERAPY:

Biologic therapy:

- See Disease Characteristics

- No prior bone marrow or peripheral blood stem cell transplantation

- At least 2 weeks since prior interferon alfa (phase I [closed to accrual as of
7/9/03])

Chemotherapy:

- See Disease Characteristics

- At least 6 weeks since prior busulfan (phase I [closed to accrual as of 7/9/03] )

- At least 2 weeks since prior cytarabine (phase I [closed to accrual as of 7/9/03])

- No concurrent chemotherapy

- Concurrent hydroxyurea allowed during the first 3 months of study

Endocrine therapy:

- Not specified

Radiotherapy:

- Not specified

Surgery:

- Not specified

Other:

- At least 4 weeks since prior investigational agents other than imatinib mesylate
(phase I [closed to accrual as of 7/9/03])

- No concurrent grapefruit juice

- Concurrent anagrelide hydrochloride allowed during the first 3 months of study

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Complete Cytogenetic Response at 6 and 12 Months (Phase II)

Outcome Description:

Cytogenetic response in terms of the percentage of Ph chromosome positive metaphases in bone marrow is defined as follows: Complete* (0% Ph-positive cells) Partial* (1-34%) Minor (35-95%) None (96-100%).

Outcome Time Frame:

At 6 and 12 months during phase II

Safety Issue:

No

Principal Investigator

Brian J. Druker, MD

Investigator Role:

Study Chair

Investigator Affiliation:

OHSU Knight Cancer Institute

Authority:

United States: Federal Government

Study ID:

CDR0000068443

NCT ID:

NCT00015847

Start Date:

April 2001

Completion Date:

May 2011

Related Keywords:

  • Leukemia
  • relapsing chronic myelogenous leukemia
  • chronic phase chronic myelogenous leukemia
  • Philadelphia chromosome positive chronic myelogenous leukemia
  • Leukemia
  • Leukemia, Myeloid
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Name

Location
Robert H. Lurie Comprehensive Cancer Center at Northwestern University Chicago, Illinois  60611
OHSU Knight Cancer Institute Portland, Oregon  97239