Proteasome Inhibition in Acute Promyelocytic Leukemia (PIAPL)

This is an interventional treatment trial for Relapsed Acute Promyelocytic Leukemia focused on measuring acute promyelocytic leukemia, arsenic trioxide, proteasome inhibition, bortezomib Read More

Inclusion Criteria:

i. Diagnosis of relapsed t(15;17)(PML-RARα) positive APL confirmed by reverse transcriptase polymerase chain reaction (RT-PCR).

ii. Normal cardiac function with normal electrocardiogram (QTc less than 500 msec) within 48 hours of study entry.

iii. Patient or guardian willing to give informed consent / assent. Must not have a psychiatric disorder(s) that would interfere with consent, study participation, or follow-up.

iv. Patients may have received hydroxyurea, 48 hours or less of all trans retnoic acid (ATRA), and 1 dose of an anthracycline and still be eligible for participation in this study.

v. Life expectancy of at least 2 weeks after entry on study. vi. No age limit for entry into study. vii. ECOG performance score 0, 1, or 2. viii. Fertile patients must agree to use an effective barrier method of contraception (e.g., latex condom, diaphragm, or cervical cap) to avoid pregnancy while on therapy and for 3 years following the discontinuation of therapy.

ix. Have a negative serum or urine pregnancy test prior to the first dose of therapeutic drugs (if patient is a female of childbearing potential). If breast feeding they should be willing to stop breast feeding.

Exclusion Criteria:

i. Intracranial bleed at diagnosis. ii. ECOG performance score 3 and above. iii. Severe uncontrolled infection, fulminant sepsis at diagnosis or documented pneumonia.

iv. History of cardiac arrhythmia; symptomatic coronary heart disease; uncontrollable arterial hypertension (diastolic blood pressure > 115 mm Hg); severe psychiatric disease or other concomitant diseases which do not comply with the criteria for the participation in the study.

v. Acute hepatitis (Bilirubin ≥ 5mg% or liver enzymes ≥ 4 times above laboratory normal value) vi. Acute renal failure or serum creatinine ≥ 2 mg% not reversed by hydration. vii. Patients suffering from an additional malignant tumor. No past history of receiving therapy for another malignancy, apart from squamous cell carcinoma or basal cell carcinoma of the skin.

viii. Pregnancy or lactation. ix. Patients with proven intolerance to the study drugs x. Inability, missing willingness or anticipated lack of compliance by the PI to participate in the study. Must not have any other severe concurrent disease and/or uncontrolled medical conditions, which, in the judgment of the investigator, could predispose patients to unacceptable safety risks or compromise compliance with the protocol.