AT9283 in Treating Young Patients With Relapsed or Refractory Acute Leukemia

NCT01431664 | Completed Phase 1

• 3 other identifiers: CDR0000709775CRUK-CR0708-12EUDRACT-2009-016952-36
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 5

Brief 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.

Conditions

Leukemia

Keywords

recurrent childhood acute lymphoblastic leukemia; recurrent childhood acute myeloid leukemia; acute leukemias of ambiguous lineage; acute undifferentiated leukemia; secondary acute myeloid leukemia

Outcome Measures

Primary Outcomes (1)

• Maximum-tolerated dose and recommended phase II dose of multikinase inhibitor AT9283

Secondary Outcomes (5)

• Adverse events to multikinase inhibitor AT9283 and grading severity according to NCI CTCAE Version 4.02

• Partial remission, complete remission, or complete remission with incomplete bone marrow recovery using disease-specific criteria based on ANC, platelets, and % blasts in the bone marrow

• Plasma concentration measurement of multikinase inhibitor AT9283

• Tertiary outcome(s) - Ex vivo and in vivo measurement of kinase inhibition using Plasma Inhibitory Activity (PIA) assay, phosphorylated STAT5 assay, and skin-punch biopsy (measuring pHH3, p53, PCNA, Ki67 levels)

• Results of established and novel prognostic biomarkers (genetic mutations of JAK 1, 2, 3, FLT3, IKAROS, and BCR/ABL) linking to observed responses

Interventions

multikinase inhibitor AT9283 DRUG

laboratory biomarker analysis OTHER

pharmacological study OTHER

Eligibility Criteria

• Age: Up to 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Cancer Research UK: lead

Study Sites (5)

Royal Marsden Hospital

Surrey, London, SM2 5PT, United Kingdom

Location

Birmingham Children's Hospital

Birmingham, B4 6NH, United Kingdom

Location

Leeds General Infirmary

Leeds, LS1 3EX, United Kingdom

Location

Royal Manchester Children's Hospital

Manchester, M13 9WL, United Kingdom

Location

Great North Children's Hospital, Royal Victoria Infirmary

Newcastle upon Tyne, NE1 4LP, United Kingdom

Location

MeSH Terms

Conditions

Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Biphenotypic, Acute

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Josef Vormoor

  Sir James Spence Institute of Child Health at Royal Victoria Infirmary

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Masking: NONE
• Purpose: TREATMENT
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 8, 2011
• First Posted: September 9, 2011
• Study Start: September 1, 2011
• Primary Completion: July 1, 2014
• Study Completion: July 1, 2014
• Last Updated: December 2, 2014

Record last verified: 2014-12

Locations

GB (5)