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A Pilot Phase II Study of PHA-739358 in Patients With Chronic Myeloid Leukemia Relapsing on Gleevec or c-ABL Therapy

Phase 2
18 Years
Open (Enrolling)

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Trial Information

A Pilot Phase II Study of PHA-739358 in Patients With Chronic Myeloid Leukemia Relapsing on Gleevec or c-ABL Therapy


- 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

- 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

- 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

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.

Inclusion Criteria


- 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


- 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

- Myocardial infarction

- Stroke

- Transient ischemic attack

- Pulmonary embolism

- Noncatheter-related deep-vein thrombosis


- 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

Type of Study:


Study Design:

Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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

Safety Issue:


Principal Investigator

Ronald Paquette, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Jonsson Comprehensive Cancer Center


United States: Food and Drug Administration

Study ID:




Start Date:

March 2007

Completion Date:

Related Keywords:

  • Leukemia
  • accelerated phase chronic myelogenous leukemia
  • blastic phase chronic myelogenous leukemia
  • chronic phase chronic myelogenous leukemia
  • relapsing chronic myelogenous leukemia
  • Leukemia
  • Leukemia, Myeloid
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive



Jonsson Comprehensive Cancer Center at UCLA Los Angeles, California  90095-1781