AAML1331

Principal Investigator: Phillip Barnette
Keywords: Pediatrics , Oncology , Acute Promyelocytic Leukemia , APL Department: Pediatric Administration
IRB Number: 00085240 Co Investigator:  
Specialty: Oncology
Sub Specialties:
Recruitment Status: Recruiting

Contact Information

Jennifer Craig
jennifer.craig@imail.org
8016624715

Brief Summary

1.1 Primary Aims

1.1.1 To eliminate exposure to conventional chemotherapy (including anthracyclines), for patients with standard risk APL, through use of ATO and ATRA based therapy while achieving an event free survival (EFS) that is not inferior compared to historical controls.

1.1.2 To significantly reduce exposure to conventional chemotherapy, and in particular, anthracycline exposure, for patients with high risk APL, through use of ATO and ATRA based therapy while achieving an event free survival that is not inferior compared to historical controls.

1.2 Exploratory Aims

1.2.1 To analyze the clinical impact of FLT3 mutations in pediatric APL.

1.2.2 To correlate clinical outcomes with the kinetics of reduction in PML/RARα transcript level by quantitative RT-PCR (RQ-PCR) in bone marrow and peripheral blood samples from diagnosis to time points during therapy.

1.2.3 To monitor incidence of coagulopathy complications, utilizing standardized conventional supportive care, and correlate with a battery of coagulation testing.

1.2.4 To evaluate the neurocognitive outcomes of patients treated on this protocol using patient-completed, performance-based measures of neuropsychological functioning and parent questionnaire report.

Inclusion Criteria

1. Age

Patient must be ≥ 12 months and < 22 years of age at first diagnosis of APL.

2. Diagnosis

• Patients must be newly diagnosed with a clinical diagnosis of APL (initially by morphology of bone marrow or peripheral blood). Bone marrow is highly preferred but in cases where marrow cannot be obtained at diagnosis, peripheral blood will be accepted.

• If the RQ-PCR results are known at the time of study enrollment, the patient must demonstrate the PML-RARα transcript by RQ-PCR to be eligible.

3. Prior Therapy

• Patients may receive up to a maximum of 5 days of pre-treatment with ATRA prior to administration of protocol therapy.

• Treatment with hydroxyurea, corticosteroids (any route) and intrathecal cytarabine prior to beginning protocol directed therapy is allowed. However, it should be noted that lumbar puncture and intrathecal therapy at initial diagnosis of APL is not recommended due to the possible complications of coagulopathy.

Exclusion Criteria

1. Secondary APL

Patients with secondary APL are excluded. This includes all patients with APL that may have resulted from prior treatment (chemotherapy or radiation).

2. Isolated Myeloid Sarcoma

Patients with isolated myeloid sarcoma (myeloblastoma, chloroma, including leukemia cutis) but without evidence of APL by bone marrow or peripheral blood morphology are excluded.

3. EKG Abnormalities

• Patients with a pre-existing diagnosis of a prolonged QT syndrome (even if QTc is normal at the time of APL diagnosis) are excluded due to the use of arsenic trioxide, which can prolong the QT interval.

• Patients with a baseline QTc of > 450 msec are excluded. Bazett’s formula is to be used for measurement of the corrected QT interval: the QT interval (msec) divided by the square root of the RR interval (msec).

• Patients with a history or presence of significant ventricular or atrial tachyarrhythmia are excluded.

• Patients with right bundle branch block plus left anterior hemiblock, bifascicular block are excluded.

4. Renal Dysfunction

Patients with serum creatinine > 3.0 mg/dL and patients on active dialysis for renal dysfunction are excluded.

5. Prior Chemotherapy

Patients who have received treatment with any other cytotoxic chemotherapy prior to beginning protocol therapy (other than those listed above, inclusion item 3) are excluded.

6. Pregnancy and Breast Feeding

Female patients who are pregnant are excluded. Treatment under this protocol would expose an unborn child to significant risks. Patients should not be pregnant or plan to become pregnant while on treatment. There is an extremely high risk of fetal malformation if pregnancy occurs while on ATRA in any amount, even for short periods. A pregnancy test prior to enrollment is required for female patients of childbearing potential.

Lactating females who plan to breastfeed their infants are excluded.

Sexually active patients of reproductive potential who have not agreed to be abstinent or use 2 forms of effective contraception during treatment through 1 month off therapy are excluded.