This will be an open label, multi-center study of up to 77 patients with CML in chronic,
accelerated or blast phase who have developed resistance to or have failed previous
treatment with Gleevec (imatinib mesylate). Because these patients may still be sensitive to
Gleevec, adding Homoharringtonine may restore a response to Gleevec or the combined
treatment may promote a better response than using Gleevec alone.
Every 4 weeks, the study medicine Homoharringtonine will be given by vein daily for 5 days
along with continuing daily doses of the approved medicine Gleevec taken by mouth. The
safety and effectiveness of this combined treatment in CML patients will be studied.
Patients who do not achieve a meaningful hematologic or cytogenetic response after 4 cycles
or less will be discontinued. Otherwise, patients may continue additional cycles of this
combined treatment for a maximum of 12 cycles.
- Male or female patients 16 years or older
- Philadelphia chromosome (Ph) positive chronic myelogenous leukemia (CML) in either
chronic, accelerated or blast phase
- Patients with chronic phase CML will be either refractory (failed to achieve
hematologic or cytogenetic response) or resistant (responded initially but
subsequently lost hematologic or cytogenetic response) to prior imatinib mesylate
therapy. Failure to achieve cytogenetic response is defined as follows: no
cytogenetic response after 3 months of therapy with imatinib mesylate, no major
cytogenetic response at 12 months of therapy, loss of complete cytogenetic response
documented twice, or loss of major cytogenetic response at least once.
- Patients with accelerated or blast phase may be newly diagnosed and previously
untreated or if previously treated with imatinib mesylate, will be refractory or
resistant to this agent or have failed to achieve at least a complete hematologic or
cytogenetic response to treatment, as previously defined.
- Patients in accelerated phase will meet one or more of the following criteria:
greater than or equal to 15% through less than 30% blasts in peripheral blood or bone
marrow, greater than or equal to 30% blasts + promyelocytes in peripheral blood or
bone marrow, greater than or equal to 20% basophils in peripheral blood, platelet
count less than 100 x 1000000000/L unrelated to therapy or clonal evolution.
- CML in blast phase will be defined as greater than or equal to 30% blasts in the bone
marrow or presence of extramedullary disease
- Patients must have completed all previous anti-leukemic therapy for at least 2 weeks,
except as noted, and have fully recovered from side effects of a previous therapy,
unless disease progression necessitates early therapy. Patients may receive
leukapheresis, hydroxyurea and anagrelide for up to 24 hours prior to start of study
treatment. Patients receiving imatinib mesylate may continue to receive it
uninterrupted, except for a 3-day window at treatment cycle 1.
- Bilirubin less than or equal to 2 times the upper limit of normal (ULN); ALT less
than or equal to 3 times ULN; Creatinine less than or equal to 1.5 times ULN
- ECOG performance status 0 - 2
- Be able to comply with the requirements of the entire study
- Be able and willing to provide written informed consent prior to any study related
- Patients and their partners must use an effective contraceptive during the study
dosing period. The following are considered effective contraceptives: oral
contraceptive pill, condom, diaphragm plus spermicide, abstinence, patient or partner
surgically sterile, patient or partner more than 2 years post-menopausal, or
injectable or implantable agent/device.
- New York Heart Association (NYHA) Class III or IV heart disease, active ischemia or
any other uncontrolled cardiac condition such as angina pectoris, clinically
significant cardiac arrhythmia and requiring therapy, uncontrolled hypertension or
congestive heart failure
- Myocardial infarction in the previous 12 weeks
- Other intercurrent illness which would preclude study conduct and assessment,
including but not limited to another active malignancy, uncontrolled and active
infection, positive HIV or HTLV I/II status
- Pregnant or lactating
- Any medical or psychiatric condition which may compromise the ability to give written
informed consent or to comply with the study protocol