Homoharringtonine With Oral Gleevec in Chronic, Accelerated and Blast Phase Chronic Myeloid Leukemia (CML)
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.
Myeloid Leukemia, Chronic
Myeloid Leukemia, Chronic, Accelerated-Phase
Myeloid Leukemia, Chronic, Chronic-Phase
Drug: Imatinib Mesylate
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase II Open-Label Study of the Intravenous Administration of Homoharringtonine (CGX-635) Combined With the Oral Administration of Gleevec in the Treatment of Patients With Chronic Myeloid Leukemia (CML) in Chronic, Accelerated, and Blast Phase|
- Proportion of Participants With Accelerated Phase or Blast Phase Chronic Myeloid Leukemia (CML) Who Achieve a Meaningful Response [ Time Frame: up to month 4 ] [ Designated as safety issue: No ]
Participants in accelerated or blast phase who converted to at least CML-chronic phase.
CML in accelerated phase meets one or more of the following criteria: >=15% - <30% blasts in peripheral blood or bone marrow, >=30% blasts + promyelocytes in peripheral blood or bone marrow, >=20% basophils in peripheral blood; platelet count <100*10^9/L unrelated to therapy or clonal evolution. CML in blast phase have >=30% blasts in the bone marrow or presence of extramedullary disease.
Meaningful responses include (in descending order of health)
- Complete Hematologic Remission (CHR)
- Partial Hematologic Remission (PHR)
- Hematologic Improvement (HI)
- Partial Response (PR)
- Return to Chronic Phase (RCP). A return to chronic phase involves the disappearance of blastic phase features and a return to chronic phase CML picture, i.e., peripheral blasts <15%, peripheral blasts and promyelocytes <30%, peripheral basophils <20%, and platelets >100*10^9/L.
- Proportion of Participants With Chronic Phase Chronic Myeloid Leukemia (CML) Who Achieve a Meaningful Response [ Time Frame: up to month 4 ] [ Designated as safety issue: No ]
Participants who are not in complete hematologic remission (CHR) at study start must achieve at least a CHR, and participants who are in CHR at onset must demonstrate an improvement in their cytogenetics.
A Complete Hematologic Remission (CHR) involves normalization of the bone marrow (less than 5% blasts) and peripheral blood with white blood cells < 10*10^9/L, absolute neutrophil count >=1*10^9/L, platelets >=100*10^9/L and no peripheral blasts, promyelocytes or myelocytes. This is in addition to disappearance of all signs and symptoms of the disease.
- Number of Participants With Adverse Experiences (AEs) [ Time Frame: up to 3 years ] [ Designated as safety issue: Yes ]
Summary of participants who had adverse events (AEs), who discontinued treatment due to the AE, who had serious adverse events (SAEs), and who had SAEs that were related to treatments.
A serious adverse event is one that at any dose of the study drug or at any time during the period of observation:
- Results in death;
- Is life threatening;
- Requires inpatient hospitalization or prolongation of existing hospitalization;
- Results in persistent or significant disability/incapacity;
- Is a congenital anomaly/birth defect;
- Is medically important.
The Investigator assessed each AE for potential causal relationship between the event and study drug. An investigator assessment of possibly, probably or unknown relation is considered related.
- Participants With Complete Hematologic Remission Suppression of the Philadelphia Chromosome [ Time Frame: up to month 4 ] [ Designated as safety issue: No ]
Complete hematologic remission was further classified according to the suppression of the Philadelphia chromosome (Ph) as:
No cytogenetic response - Ph positive 100% Minimal cytogenetic response - Ph positive 35-90% Partial cytogenetic response - Ph positive 1-34% Complete cytogenetic response - Ph positive 0%
|Study Start Date:||October 2005|
|Study Completion Date:||March 2009|
|Primary Completion Date:||June 2008 (Final data collection date for primary outcome measure)|
Experimental: Homoharringtonine + Imatinib Mesylate
Participants are administered homoharringtonine (omacetaxine) 2.5 mg/m^2 by continuous 24-hour intravenous infusion daily on Days 1-5 of each 4 week treatment cycle, and imatinib mesylate (Gleevec) by mouth with a daily dose of 400 mg for participants in the chronic phase of chronic myeloid leukemia (CML) or 600 mg for participants in the accelerated or blast phase of CML.
Participants are administered homoharringtonine (omacetaxine) 2.5 mg/m^2 by continuous 24-hour intravenous (IV) infusion daily on Days 1-5 of each 4 week treatment cycle. Participants who do not achieve a meaningful hematologic or cytogenetic response by the end of the fourth cycle are discontinued from the study. Otherwise, participants may continue additional cycles of this combined treatment for a maximum of 12 cycles.
Participants who achieved a molecular or cytogenetic response, or a complete hematologic remission (CHR), could undergo subsequent cycles with a maintenance schedule of homoharringtonine 2.5 mg/m^2 by continuous 24-hour IV infusion daily for 2 days every 4 weeks. Dose escalations in subsequent cycles were allowed by one day at a time if the participant was unable to maintain CHR in the maintenance schedule.
Other Names:Drug: Imatinib Mesylate
Taken by mouth with a daily dose of 400 mg for participants in the chronic phase of chronic myeloid leukemia (CML) or 600 mg for participants in the accelerated or blast phase of CML. For the first cycle of therapy only, imatinib was started on Day 4 of homoharringtonine treatment.
Other Name: Gleevac
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00114959
|United States, Texas|
|Univ. of Texas M.D. Anderson Cancer Center|
|Houston, Texas, United States, 77030|
|Study Director:||Adam R Craig, M.D., PhD||ChemGenex Pharmaceuticals|
|Principal Investigator:||Jorge Cortes, M.D.||Univ. of TX M.D. Anderson Cancer Center|