Clinical trial NCT00844298
Conditions: Leukemia
Keywords: Philadelphia chromosome positive adult precursor acute lymphoblastic leukemia untreated adult acute lymphoblastic leukemia
Sponsor: Asan Medical Center
Start date: 2009-01-01; Completion date: 2014-07-01
Enrollment: 91 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
RATIONALE: Nilotinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving nilotinib together with combination chemotherapy may kill more cancer cells.

PURPOSE: This phase II trial is studying how well giving nilotinib together with combination chemotherapy works in treating patients with newly diagnosed acute lymphoblastic leukemia.

Detailed description:
OBJECTIVES:

Primary

* To determine the clinical efficacy of nilotinib and combination chemotherapy, in terms of hematologic and molecular complete remission (CR) rates, in patients with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia or acute mixed lineage leukemia.

Secondary

* To establish the prognostic factors for patients treated with this regimen.
* To determine the duration of CR in patients treated with this regimen.
* To determine the duration of progression-free and overall survival of these patients.
* To determine the toxicity of this regimen in these patients.

OUTLINE: This is a multicenter study. Patients are stratified according to age (15 to 64 years vs ≥ 65 years).

* Induction therapy: Patients receive daunorubicin hydrochloride IV continuously over 24 hours on days 1-3, vincristine sulfate IV on days 1 and 8, and oral prednisolone on days 1-14. Patients undergo bone marrow examination on day 14. Patients in hematologic remission proceed to consolidation therapy. Patients with residual leukemic cells \> 5% receive an additional dose of daunorubicin hydrochloride IV continuously over 24 hours on day 15 before proceeding to consolidation therapy.
* Consolidation therapy: For course 1, patients receive daunorubicin hydrochloride IV continuously over 24 hours on days 1 and 2, vincristine sulfate IV on days 1 and 8, and oral prednisolone on days 1-14. For courses 2 and 4, patients receive cytarabine IV over 2 hours and etoposide IV over 3 hours on days 1-4. For courses 3 and 5, patients receive methotrexate IV continuously over 36 hours on days 1, 2, 15, and 16 and leucovorin calcium IV every 6 hours for 3 doses and then orally until blood methotrexate levels are in a safe range.

Patients also receive oral nilotinib twice daily beginning on day 8 of induction therapy and continuing until the completion of consolidation therapy.

After completion of consolidation therapy, patients with a hematopoietic stem cell donor proceed to allogeneic hematopoietic stem cell transplantation (HSCT). Patients who do not undergo HSCT continue to receive oral nilotinib twice daily for up to 2 years after completion of consolidation therapy.

After completion of study therapy, patients are followed periodically for up to 1 year.

Arms: arm 1: Patients who were Philadelphia-positive, newly-diagnosed adult ALL and treated with nilotinib + mVPD treatment plan
Interventions: intervention 1: Nilotinib+mVPD
Intervention descriptions: intervention 1: 1. Induction:

   * Daunorubicin 90 mg/m2/day by continuous iv infusion (d1-3)
   * Vincristine 2 mg iv push (d1, 8, 15, 22)
   * Prednisolone 60 mg/m2/day po (d1-28)
   * Nilotinib 400mg bid/d (d8-)
2. Consolidation A (cycle1)

   * Daunorubicin 45 mg/m2/day by continuous iv (d1, 2)
   * Vincristine 2 mg iv (d1, 8)
   * Prednisolone 60 mg/m2/day po (d1-14)
   * Nilotinib 400mg bid/d
3. Consolidation B (cycles 2\&4)

   * Cytarabine 2,000 mg/m2/day iv over 2 hours (d1-4)
   * Etoposide 150 mg/m2/day iv over 3 hours (d1-4)
   * Nilotinib 400mg bid/d
4. Consolidation C (cycles 3\&5)

   * Methotrexate 220 mg/m2 iv bolus, then 60mg/m2/h for 36 hours (d1-2, 15-16)
   * Leucovorin followed immediately by 50 mg/m2 iv every 6hrs for three doses,
   * Nilotinib 400mg bid/d
5. Maintenance

   ◦Nilotinib 400mg bid/d (during 2 years, for patients without alloHCT)
6. Consider alloHCT

Protocol documents: