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Tasigna® (Nilotinib) Plus Multi-Agent Chemotherapy for Newly-Diagnosed Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia


Phase 2
15 Years
N/A
Open (Enrolling)
Both
Leukemia

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Trial Information

Tasigna® (Nilotinib) Plus Multi-Agent Chemotherapy for Newly-Diagnosed Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia


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.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Newly diagnosed acute lymphoblastic leukemia or acute mixed lineage leukemia

- Positive for Bcr-Abl fusion transcript (Philadelphia chromosome-positive
disease) by RT-PCR

PATIENT CHARACTERISTICS:

- ECOG performance status 0-2

- Total bilirubin < 2 mg/dL

- SGOT < 3 times upper limit of normal (ULN)

- Alkaline phosphatase ≤ 2.5 times ULN (unless considered tumor-related)

- Creatinine < 2.0 mg/dL ULN

- Serum amylase and lipase ≤ 1.5 times ULN

- Potassium, magnesium, and phosphorus normal (supplementation allowed)

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No rare hereditary problems with galactose intolerance, severe lactase deficiency, or
glucose-galactose malabsorption

- No known sensitivity to any of the study drugs

- No severe medical condition that, in the opinion of the investigator, would preclude
study participation

- No impaired cardiac function, including any of the following:

- LVEF < 45% or below the lower limit of normal by ECHO

- Long QT syndrome or known family history of long QT syndrome

- Clinically significant resting bradycardia (< 50 beats per minute)

- QTc > 450 msec on baseline ECG (using the QTcF formula)

- Myocardial infarction within the past 12 months

- Other clinically significant heart disease, including any of the following:

- Unstable angina

- Congestive heart failure

- Uncontrolled hypertension

- Uncontrolled arrhythmias

- No other primary malignant disease requiring systemic treatment

- No acute or chronic liver, pancreatic, or severe renal disease

- No other severe and/or life-threatening medical disease

- No history of significant congenital or acquired bleeding disorder unrelated to
cancer

- No impairment of gastrointestinal (GI) function or GI disease that may significantly
alter the absorption of study drug

- No history of non-compliance

PRIOR CONCURRENT THERAPY:

- More than 30 days since prior investigational agents

- No concurrent medications that have the potential to prolong the QTc interval

- No concurrent strong CYP3A4 inhibitors

- No concurrent therapeutic coumarin derivatives

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

Proportion of patients achieving hematologic and molecular complete remission (CR) after induction therapy

Outcome Description:

approximate time: at the recovery of cytopenia

Outcome Time Frame:

1 month

Safety Issue:

No

Principal Investigator

Kyoo H. Lee, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Asan Medical Center

Authority:

South Korea: Korea Food and Drug Administration (KFDA)

Study ID:

CDR0000632225

NCT ID:

NCT00844298

Start Date:

January 2009

Completion Date:

Related Keywords:

  • Leukemia
  • Philadelphia chromosome positive adult precursor acute lymphoblastic leukemia
  • untreated adult acute lymphoblastic leukemia
  • Leukemia
  • Leukemia, Lymphoid
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Philadelphia Chromosome

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