AT9283 in Treating Young Patients With Relapsed or Refractory Acute Leukemia

• Status: Completed
• Trial end date: 2014-07-01
• Target enrollment: 0
• Participant gender: All

Summary

RATIONALE: AT9283 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

PURPOSE: This phase I/IIa clinical trial is studying the side effects and best dose of AT9283 in treating young patients with relapsed or refractory acute leukemia.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Cancer Research UK

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed acute leukemia according to the following criteria:

• Acute lymphoblastic leukemia (ALL) meeting any of the following criteria:

• Second relapse

• Refractory to induction therapy for first relapse

• Third or subsequent relapse

• Acute myeloid leukemia (AML) meeting any of the following criteria:

• Second or subsequent relapse

• Refractory to an induction therapy for first relapse

• Without a curative treatment option

• Other type of acute leukemia meeting any of the following criteria:

• First or subsequent relapse

• Refractory to induction therapy

• Not eligible for any therapy of higher curative potential

• No chronic myeloid leukemia (CML)

• Patients in relapse must have ≥ 5% blasts in the bone marrow

• Patients with refractory disease following induction must have ≥ 20% blasts in the bone marrow

• No evidence of CNS disease

PATIENT CHARACTERISTICS:

• Karnofsky performance status (PS) 50-100% OR Lansky PS 50-100%

• Life expectancy ≥ 8 weeks

• Serum bilirubin < 1.5 times upper limit of normal (ULN)

• ALT or AST < 2.5 times ULN (5 times ULN if due to leukemic infiltration of the liver)

• Creatinine clearance ≥ 60 mL/min

• Not pregnant or nursing

• Negative pregnancy test

• Fertile female patients must use 2 of the following combined forms of contraception (oral, injected, or implanted hormonal contraception and condom OR intra-uterine device and condom OR diaphragm with spermicidal gel and condom) before, during, and for 6 months after completion of study therapy

• Male patients must use 1 form of highly effective contraception (condom plus spermicidal gel) during and for 6 months after completion of study therapy

• Men with pregnant or lactating partners should be advised to use barrier-method contraception (condom plus spermicidal gel)

• No serological positivity for hepatitis B, hepatitis C, or HIV

• No congenital heart disease, with the exception of patent foramen ovale or small muscular ventricular septal deficit (within the first year of life)

• No uncontrolled arterial hypertension (defined as a systolic blood pressure [BP] and/or diastolic BP ≥ 95th percentile for age and height)

• No fractional shortening of ≤ 29% on echocardiogram

• No active graft-vs-host disease

• No current non-malignant systemic disease considered high medical risk, including any of the following:

• Active uncontrolled infection

• Unstable or uncompensated respiratory or cardiac condition that makes study participation undesirable

• No other condition that, in the Investigator's opinion, would not make the patient a good candidate for the clinical trial

PRIOR CONCURRENT THERAPY:

• Recovered from toxicity of prior therapy, including toxicity following hematopoietic stem cell transplantation

• Alopecia or certain grade 1 toxicities allowed at the discretion of the Investigator

• A maximum of 2 days of hydroxycarbamide 10-20 mg/kg/day (or according to local practice) in patients with AML and hyperleukocytosis allowed

• At least 7 days since prior investigational drugs (except antibodies for which a 4-week window must be observed)

• At least 7 days since prior protein kinase inhibitors and intrathecal therapy

• Concurrent intrathecal therapy allowed from course 2 onwards in patients with ALL

• At least 14 days since prior cytotoxic therapy, including vincristine and other anti-neoplastics

• No prior major thoracic or abdominal surgery from which the patient has not yet recovered

• No prior aurora kinase inhibitor

• No concurrent steroid therapy

• Multikinase inhibitor AT9283 administration may be commenced once steroids have started; however, steroids may not be started once multikinase inhibitor AT9283 has started

• Up to 5 days of prior oral dexamethasone (6 mg/m^2) for patients with ALL experiencing a rapid rise in blast count allowed

• No other concurrent interventional clinical study

• Participation in an observational study allowed

• No other concurrent anticancer therapy or investigational drugs