PHA-739358 in Treating Patients With Chronic Myelogenous Leukemia That Relapsed After Imatinib Mesylate or c-ABL Therapy

NCT00335868 | Unknown Phase 2

• 3 other identifiers: CDR0000486219UCLA-0601009-01NERVIANO-AURA-6202-005
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

RATIONALE: PHA-739358 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. PURPOSE: This phase II trial is studying how well PHA-739358 works in treating patients with chronic myelogenous leukemia that relapsed after imatinib mesylate or c-ABL therapy.

Conditions

Leukemia

Keywords

accelerated phase chronic myelogenous leukemia; blastic phase chronic myelogenous leukemia; chronic phase chronic myelogenous leukemia; relapsing chronic myelogenous leukemia

Outcome Measures

Primary Outcomes (6)

• Antileukemic response in terms of complete hematological response, no evidence of leukemia, or return to chronic phase

• Overall safety profile of PHA-739358 by type, severity, timing, and relatedness of adverse events and laboratory abnormalities

• Pharmacokinetics of this drug and its N-oxide metabolite PHA-816359 by measuring their plasma concentration at different times after dosing

• Changes in histone H3 and CRKL phosphorylation

• Correlation between changes in degree of histone H3 and CRKL phosphorylation and concurrent PHA-739358 concentrations and/or hematological response

• Complete, partial, or minor cytogenetic response in bone marrow

Interventions

danusertib DRUG

laboratory biomarker analysis OTHER

pharmacological study OTHER

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: * Diagnosis of chronic myelogenous leukemia confirmed by bone marrow biopsy * Chronic, accelerated, or blastic phase disease * May have T315I mutation in BCR-ABL kinase * Relapsed after prior imatinib mesylate or c-ABL therapy * No CNS leukemia PATIENT CHARACTERISTICS: * ECOG performance status 0-2 * Blood pressure ≤ 140/90 mm Hg (with or without hypertension treatment for ≥ 1 week) * Transaminases ≤ 2.5 times upper limit of normal (ULN) * Bilirubin ≤ 1.5 times ULN * Creatinine ≤ 1.5 times ULN * No known history of HIV infection * No active uncontrolled infection * No grade 3 or 4 bleeding * LVEF ≥ 45% by MUGA or ≥ 40% by transthoracic echocardiography * No medical or psychiatric condition or laboratory abnormalities that would limit study compliance or increase risk during study participation * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception during and for 90 (female) or 180 (male) days after completion of study treatment * No significant cardiovascular disease (i.e., uncontrolled arrhythmias or unstable angina) within the past 6 months * No major thromboembolic event within the past 6 months, including any of the following: * Myocardial infarction * Stroke * Transient ischemic attack * Pulmonary embolism * Noncatheter-related deep-vein thrombosis PRIOR CONCURRENT THERAPY: * Recovered from all acute toxic effects (excluding alopecia) of prior therapy * More than 2 weeks since prior chemoimmunotherapy * Hydroxyurea must be discontinued 1 day prior to study therapy * More than 4 weeks since prior major surgery * No other concurrent approved or investigational anticancer treatment, including chemotherapy, biologic response modifiers, hormones, or immunotherapy * No other concurrent investigational drugs * No concurrent participation in another treatment clinical trial

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

Sponsors & Collaborators

• Jonsson Comprehensive Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Jonsson Comprehensive Cancer Center at UCLA

Los Angeles, California, 90095-1781, United States

Location

MeSH Terms

Conditions

Leukemia; Leukemia, Myeloid, Accelerated Phase; Blast Crisis; Leukemia, Myeloid, Chronic-Phase

Interventions

danusertib

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid; Myeloproliferative Disorders; Bone Marrow Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Cell Transformation, Neoplastic; Carcinogenesis; Neoplastic Processes

Study Officials

• Ronald Paquette, MD

  Jonsson Comprehensive Cancer Center

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Masking: NONE
• Purpose: TREATMENT
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: June 8, 2006
• First Posted: June 12, 2006
• Study Start: March 1, 2007
• Primary Completion: December 1, 2009
• Last Updated: December 18, 2013

Record last verified: 2009-07

Locations

US (1)