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A Phase II Study of Newly Diagnosed Patients With BCR/ABL (+) Chronic Myelogenous Leukemia Treated With Combined Homoharringtonine (NSC #141633) and Low-Dose Cytarabine

Phase 2
16 Years
Not Enrolling
Chronic Myelogenous Leukemia, BCR-ABL1 Positive, Chronic Phase Chronic Myelogenous Leukemia

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Trial Information

A Phase II Study of Newly Diagnosed Patients With BCR/ABL (+) Chronic Myelogenous Leukemia Treated With Combined Homoharringtonine (NSC #141633) and Low-Dose Cytarabine


I. To estimate the hematologic and cytogenetic response rate of newly diagnosed patients
with BCR/ABL (+) chronic myelogenous leukemia (CML) treated with combined homoharringtonine
(omacetaxine mepesuccinate) and low dose cytarabine.

II. To estimate the toxicity of these two drugs given in combination in a cooperative group


I. To assess duration of hematological response and incidence of hematological progression
for all patients.

II. To assess duration of cytogenetic response in patients continuing protocol therapy
beyond the initial nine months.

III. To use quantitative Southern blot monitoring of blood samples to monitor molecular
response rates in patients entered onto CALGB treatment studies for CML.

IV. To compare quantitative Southern blot results of blood samples with marrow cytogenetics
at the time of complete molecular response.

V. To use RT-PCR to monitor the frequency of residual disease in patients who have achieved
a complete blood Southern blot and marrow cytogenetic response (elimination of BCR/ABL
positivity by Southern blot and absence of the Philadelphia chromosome by cytogenetics).


Patients receive cytarabine and homoharringtonine concurrently by continuous intravenous
infusion for 7 days. Courses repeat every 28 days. Patients receive a minimum of 9 courses
of therapy in the absence of disease progression and unacceptable toxicity. Patients who are
major cytogenetic responders at 9 months may continue therapy or switch to interferon. Minor
cytogenetic responders are switched to interferon, and nonresponders are removed from
therapy and given the option to switch to interferon.

Patients are followed every 6 months for 10 years.

Inclusion Criteria:

- Histologic diagnosis of chronic myelogenous leukemia (CML) in chronic phase; patients
in either accelerated or blastic phases are not eligible; clonal cytogenetic
evolution alone does not exclude patients

- Patients must meet one or more of the following criteria:

- Cytogenetically determined Philadelphia chromosome (Ph+)

- BCR/ABL protein detectable by immunoblotting

- Polymerase chain reaction (PCR) positive fusion transcripts for BCR/ABL

- BCR/ABL translocation present by fluorescence in situ hybridization (FISH)

- Registration within eight weeks of the diagnosis and confirmation of Ph+ or BCR/ABL+

- No more than eight weeks of prior hydroxyurea therapy

- No previous therapy with homoharringtonine (HHT)

- No prior treatment for CML with agents other than hydroxyurea; thus, prior treatment
for CML with agents such as interferon, busulfan or cytarabine will render patients

- Must not be a candidate for an early allogeneic bone marrow transplant; potential
transplant candidates must be counseled about alternative donor transplants and must
decline that treatment option

- ECOG performance status 0-2

- Non-pregnant and non-nursing; treatment under this protocol would expose an unborn
child to significant risks; women and men of reproductive potential should agree to
use an effective means of birth control

- Bilirubin =< x upper limit of normal

- Creatinine =< 1.5 mg/dl

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Complete cytogenetic, major cytogenetic, and hematologic response rate

Outcome Description:

Two separate single-stage Fleming designs will be used to test hypotheses regarding the major cytogenetic response rate and the complete cytogenetic response rate. Calculated and presented with their 95% confidence intervals.

Outcome Time Frame:

Up to 9 months

Safety Issue:


Principal Investigator

Richard Stone

Investigator Role:

Principal Investigator

Investigator Affiliation:

Cancer and Leukemia Group B


United States: Food and Drug Administration

Study ID:




Start Date:

March 1999

Completion Date:

Related Keywords:

  • Chronic Myelogenous Leukemia, BCR-ABL1 Positive
  • Chronic Phase Chronic Myelogenous Leukemia
  • Leukemia
  • Leukemia, Myeloid
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive
  • Leukemia, Myeloid, Chronic-Phase



Dana-Farber Harvard Cancer Center Boston, Massachusetts  02115