Phase I Study Of The Combination Of 17-AAG And Imatinib Mesylate (Gleevec) In Patients With Blastic Phase, Accelerated Phase Of Chronic Mesylate Leukemia (CML) Or Patients With Chronic Phase CML Who Have Not Achieved A Cytogenetic Response With Imatinib Mesylate


Phase 1
18 Years
N/A
Not Enrolling
Both
Leukemia

Thank you

Trial Information

Phase I Study Of The Combination Of 17-AAG And Imatinib Mesylate (Gleevec) In Patients With Blastic Phase, Accelerated Phase Of Chronic Mesylate Leukemia (CML) Or Patients With Chronic Phase CML Who Have Not Achieved A Cytogenetic Response With Imatinib Mesylate


OBJECTIVES:

- Determine the maximum tolerated dose and dose-limiting toxicity of
17-N-allylamino-17-demethoxygeldanamycin (17-AAG) when administered with imatinib
mesylate in patients with chronic myelogenous leukemia.

- Determine the pharmacokinetics of this regimen in these patients.

OUTLINE: This is an open-label, nonrandomized, multicenter, dose-escalation study of
17-N-allylamino-17-demethoxygeldanamycin (17-AAG).

Patients receive oral imatinib mesylate on days 1-21 and 17-AAG IV over 1 hour on days 1, 4,
8, and 12. Courses repeat every 21 days in the absence of disease progression or
unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of 17-AAG until the maximum tolerated dose
(MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6
patients experience dose-limiting toxicity. Once the MTD is determined, an additional cohort
of 6-10 patients receives treatment at the recommended phase II dose.

PROJECTED ACCRUAL: Approximately 21-42 patients will be accrued for this study within 1.5
years.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Diagnosis of chronic myelogenous leukemia, including any of the following phases:

- Blastic phase

- Greater than 30% blasts in the peripheral blood or bone marrow

- Previously untreated disease OR refractory to or relapsed after most recent
therapy

- Accelerated phase, defined by 1 of the following:

- At least 15, but less than 30%, blasts in the peripheral blood or bone
marrow

- At least 30% blasts and promyelocytes in the peripheral blood or bone
marrow

- Greater than 20% peripheral blood basophilia

- Chronic phase

- No major cytogenetic response (less than 65% Philadelphia chromosome
negative) after 12 months of prior imatinib mesylate therapy

- Philadelphia chromosome positive by routine cytogenetics

PATIENT CHARACTERISTICS:

Age

- 18 and over

Performance status

- ECOG 0-2

Life expectancy

- At least 3 months

Hematopoietic

- Not specified

Hepatic

- Bilirubin no greater than 1.5 mg/dL

- ALT and AST no greater than 2.5 times upper limit of normal

Renal

- Creatinine less than 1.5 mg/dL

Cardiovascular

- No symptomatic congestive heart failure

- No unstable angina pectoris

- No cardiac arrhythmia

Other

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No known allergy to eggs

- Able to swallow pills

- No ongoing or active infection

- No psychiatric illness or social situation that would preclude study compliance

- No other concurrent uncontrolled medical illness

PRIOR CONCURRENT THERAPY:

Biologic therapy

- No prior stem cell transplantation

Chemotherapy

- More than 4 weeks since prior chemotherapy (except hydroxyurea or anagrelide) (at
least 6 weeks for nitrosoureas or mitomycin)

Endocrine therapy

- Not specified

Radiotherapy

- More than 4 weeks since prior radiotherapy

Surgery

- No prior liver, kidney, or lung transplantation

- More than 14 days since prior major surgery (e.g., thoracotomy or intra-abdominal
surgery)

Other

- Prior imatinib mesylate administered within the past 4 weeks is allowed

- No concurrent tacrolimus or cyclosporine as immunosuppressive agents

- No other concurrent investigational agents

- No concurrent combination antiretroviral therapy for HIV-positive patients

- No concurrent agents that alter CYP3A4 activity, including any of the following:

- Grapefruit juice

- Ketoconazole

- Fluconazole

- Itraconazole

- Erythromycin

- Clarithromycin

- Cimetidine

- Terfenadine

- Astemizole

- HIV protease inhibitors (e.g., indinavir and nelfinavir)

Type of Study:

Interventional

Study Design:

Masking: Open Label, Primary Purpose: Treatment

Principal Investigator

Charles A. Schiffer, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Barbara Ann Karmanos Cancer Institute

Authority:

United States: Federal Government

Study ID:

CDR0000315521

NCT ID:

NCT00066326

Start Date:

June 2003

Completion Date:

September 2005

Related Keywords:

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

Name

Location
Barbara Ann Karmanos Cancer Institute Detroit, Michigan  48201