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A Phase I-II Study Evaluating the Safety and Efficacy of Imatinib Mesylate (Gleevec) Combined With Reinduction Chemotherapy Using Mitoxantrone, Etoposide and Cytarabine in Patients With Relapsed/Refractory C-kit Positive Acute Myeloid Leukemia


Phase 1/Phase 2
18 Years
65 Years
Not Enrolling
Both
Leukemia

Thank you

Trial Information

A Phase I-II Study Evaluating the Safety and Efficacy of Imatinib Mesylate (Gleevec) Combined With Reinduction Chemotherapy Using Mitoxantrone, Etoposide and Cytarabine in Patients With Relapsed/Refractory C-kit Positive Acute Myeloid Leukemia


Induction therapy:

- Imatinib 200-400 mg p.o. daily x 10 days, Days 1-10 (see dose escalation scheme in
Section 5.4 below).

- Mitoxantrone 10 mg/m2 daily x 5 days, Days 4-8.

- Etoposide 100 mg/m2 daily x 5 days, Days 4-8.

- Cytarabine 1.5 grams/m2 q12h x 4 doses, Days 9-10 (for patients aged 60 years and over,
1.0 gram/m2).

Only one induction course will be permitted. Only patients achieving CR will proceed to
consolidation and maintenance.

Consolidation therapy, maximum 2 cycles (for patients achieving CR):

- Imatinib 200-400 mg p.o. daily x 8 days, Days 1-8 (see dose escalation scheme in
Section 5.4 below).

- Mitoxantrone 12 mg/m2 daily x 2 days, Days 4-5.

- Cytarabine 3 grams/m2 q12h x 6 doses, Days 4,6,8. For patients aged 60 years and over,
the dose will be reduced to 1.5 grams/m2.

Maintenance therapy (for patients still in CR at end of consolidation):

Imatinib 600 mg p.o. daily, until relapse or toxicity (see dose modification criteria in
Section 5.6.6 below). Patients must receive at least one consolidation cycle before being
permitted to proceed to maintenance therapy (see Section 5.6 for details). Maintenance
therapy with imatinib will be provided for a maximum period of 1 year.

Dose escalation scheme:

Imatinib will be used during induction and consolidation at one of the following dose
levels:

Level -1 100 mg daily Level 1 200 mg daily Level 2 300 mg daily Level 3 400 mg daily


Inclusion Criteria:



- AML, all subtypes except APL.

- Prior induction therapy consisting of cytarabine 100-200 mg/m2 plus an anthracycline.

- One of the following:

- persistent leukemia after induction therapy.

- relapse within two years of achieving complete remission with induction therapy.
Any consolidation therapy is acceptable, including stem cell transplantation.

- At least 10% bone marrow blasts, or biopsy confirmed extramedullary disease.

- Positivity for c-kit (CD117) in at least 30% of blasts as measured by flow cytometry.

- Aged 18-65.

- ECOG performance status < 3 (see Appendix I).

- No chemotherapy within the previous four weeks, other than hydroxyurea to control
counts. If hydroxyurea is used, it must be stopped at least 24 hours prior to
starting imatinib.

- Able to given informed consent.

Exclusion Criteria:

- Active uncontrolled infection.

- Active CNS leukemia.

- Serum creatinine > 200 umol/L.

- Serum bilirubin > 1.5 x ULN, AST or ALT > 2x ULN.

- Left ventricular ejection fraction < 50%.

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

Toxicity (hematologic and non-hematologic) of the combination of Imatinib and Chemotherapy consisting of Mitoxantrone, Etoposide and Ara-c

Outcome Description:

Hematologic toxicity Number of days to ANC > 0.5 and 1.0. Number of days until platelets > 20 and > 50, independent of platelet transfusions. Number of days until RBC transfusion independent. Non-hematologic toxicity, as per NCI common toxicity criteria Hematologic dose-limiting toxicity (DLT) defined as > 40 days to ANC > 0.5 or platelets > 20 independent of transfusions.

Outcome Time Frame:

2 years

Safety Issue:

Yes

Authority:

Canada: Ethics Review Committee

Study ID:

04-0147-C

NCT ID:

NCT01126814

Start Date:

July 2004

Completion Date:

April 2010

Related Keywords:

  • Leukemia
  • Gleevec
  • c-kit
  • aml
  • Leukemia
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid

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