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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified July 2009 by National Cancer Institute (NCI).
Recruitment status was  Active, not recruiting
Sponsor:
Collaborator:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00335868
First received: June 8, 2006
Last updated: December 17, 2013
Last verified: July 2009
  Purpose

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.


Condition Intervention Phase
Leukemia
Drug: danusertib
Other: laboratory biomarker analysis
Other: pharmacological study
Phase 2

Study Type: Interventional
Study Design: Masking: Open Label
Primary Purpose: Treatment
Official Title: A Pilot Phase II Study of PHA-739358 in Patients With Chronic Myeloid Leukemia Relapsing on Gleevec or c-ABL Therapy

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Antileukemic response in terms of complete hematological response, no evidence of leukemia, or return to chronic phase [ Designated as safety issue: No ]
  • Overall safety profile of PHA-739358 by type, severity, timing, and relatedness of adverse events and laboratory abnormalities [ Designated as safety issue: Yes ]
  • Pharmacokinetics of this drug and its N-oxide metabolite PHA-816359 by measuring their plasma concentration at different times after dosing [ Designated as safety issue: No ]
  • Changes in histone H3 and CRKL phosphorylation [ Designated as safety issue: No ]
  • Correlation between changes in degree of histone H3 and CRKL phosphorylation and concurrent PHA-739358 concentrations and/or hematological response [ Designated as safety issue: No ]
  • Complete, partial, or minor cytogenetic response in bone marrow [ Designated as safety issue: No ]

Estimated Enrollment: 16
Study Start Date: March 2007
Estimated Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

  • Explore the clinical efficacy of PHA-739358, in terms of hematological response lasting ≥ 4 weeks, in patients with chronic myelogenous leukemia that relapsed after imatinib mesylate or c-ABL therapy.
  • Explore the safety profile of this drug in these patients.
  • Explore the pharmacokinetic profile of this drug and its N-oxide metabolite PHA-816359 in plasma.
  • Explore the modulation of histone H3 and CRKL phosphorylation after PHA-739358 administration.
  • Explore the relationship between plasma drug levels and the modulation of histone H3 and CRKL phosphorylation.
  • Explore the clinical efficacy of this drug, in terms of cytogenetic response in bone marrow.
  • Explore response depending on status of T315I mutation in BCR-ABL kinase.

OUTLINE: This is a pilot, open-label, multicenter study.

Patients receive PHA-739358 IV over 6 hours on days 1, 8, and 15. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients benefitting from treatment may receive additional courses at the discretion of the investigator.

Patients undergo blood collection and bone marrow biopsies periodically for pharmacologic and biomarker correlative studies.

After completion of study treatment, patients are followed every 3 months for 1 year.

PROJECTED ACCRUAL: A total of 16 patients will be accrued for this study.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00335868

Locations
United States, California
Jonsson Comprehensive Cancer Center at UCLA
Los Angeles, California, United States, 90095-1781
Sponsors and Collaborators
Jonsson Comprehensive Cancer Center
Investigators
Study Chair: Ronald Paquette, MD Jonsson Comprehensive Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Ronald Paquette, Jonsson Comprehensive Cancer Center at UCLA
ClinicalTrials.gov Identifier: NCT00335868     History of Changes
Other Study ID Numbers: CDR0000486219, UCLA-0601009-01, NERVIANO-AURA-6202-005
Study First Received: June 8, 2006
Last Updated: December 17, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):
accelerated phase chronic myelogenous leukemia
blastic phase chronic myelogenous leukemia
chronic phase chronic myelogenous leukemia
relapsing chronic myelogenous leukemia

Additional relevant MeSH terms:
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia
Neoplasms by Histologic Type
Neoplasms
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases

ClinicalTrials.gov processed this record on September 16, 2014