Open Label Study of Subcutaneous Homoharringtonine (Omacetaxine Mepesuccinate) in Patients With Advanced CML
Primary Purpose
Chronic Myeloid Leukemia
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Omacetaxine mepesuccinate
Sponsored by
About this trial
This is an interventional treatment trial for Chronic Myeloid Leukemia focused on measuring CML, HHT, Homoharringtonine, Omacetaxine
Eligibility Criteria
Inclusion Criteria:
- Male or female patients, age 18 years or older
- Philadelphia chromosome (Ph) positive chronic myelogenous leukemia in either chronic, accelerated, or blast phase
- Patients will have either failed, demonstrated intolerance, or a combination of prior failure and intolerance, to prior treatments with at least two tyrosine kinase inhibitors (TKI's). Failure of TKI treatment may either be primary (never achieved a response) or secondary resistance (loss of response).
- Acceptable Renal and Liver Function
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
- Sexually active patients and their partners must use an effective double barrier method of contraception
Exclusion Criteria:
- New York Heart Association classification (NYHA) class III or IV heart disease, active ischemia or any other uncontrolled cardiac condition
- Myocardial infarction in the previous 12 weeks.
- Other concurrent illness which would preclude study conduct and assessment
- uncontrolled and active infection, and positive HIV or positive HTLV I/II status, whether on treatment or not.
- 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.
- Lymphoid Ph+ blast crisis
- Patient is enrolled in another clinical investigation within 30 days of enrollment or is receiving another investigational agent
Sites / Locations
- Teva Investigational Site 303
- Teva Investigational Site 308
- Teva Investigational Site 311
- Teva Investigational Site 302
- Teva Investigational Site 305
- Teva Investigational Site 310
- Teva Investigational Site 301
- Teva Investigational Site 314
- Teva Investigational Site 313
- Teva Investigational Site 309
- Teva Investigational Site 329
- Teva Investigational Site 321
- Teva Investigational Site 322
- Teva Investigational Site 320
- Teva Investigational Site 324
- Teva Investigational Site 328
- Teva Investigational Site 323
- Teva Investigational Site 327
- Teva Investigational Site 325
- Teva Investigational Site 331
- Teva Investigational Site 330
- Teva Investigational Site 350
- Teva Investigational Site 371
- Teva Investigational Site 370
- Teva Investigational Site 390
- Teva Investigational Site 360
- Teva Investigational Site 361
- Teva Investigational Site 380
- Teva Investigational Site 340
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
OMA
Arm Description
Omacetaxine mepesuccinate (OMA) Induction: 1.25mg/m^2 subcutaneously twice daily for 14 consecutive days, every 28 days for up to six cycles. Omacetaxine mepesuccinate (OMA) Maintenance: 1.25mg/m^2 subcutaneously twice daily for 7 consecutive days, every 28 days for up to 24 months.
Outcomes
Primary Outcome Measures
Percentage of Participants Achieving an Overall Hematologic Response by Subpopulation and Total Population
Subpopulations reflect chronic myeloid leukemia (CML) phases at the time of enrollment: chronic, accelerated, and blast phase. Primary endpoints as adjudicated by the Data Monitoring Committee were used for the primary analyses.
Overall hematologic response for chronic phase participants includes confirmed complete hematologic response (CHR). Overall hematologic response for accelerated or blast phase participants includes confirmed complete hematologic response (CHR), no evidence of leukemia (NEL), or return to chronic phase (RCP). Hematologic response must last >= 8 weeks to be considered meaningful.
Response rates by disease phase were examined relative to an a priori value of 2.5% using a one-sided lower 95% exact binomial confidence limit. If the lower limit from the one-sided lower 95% confidence limit exceeds 2.5%, the observed response rate will have exceeded the minimum threshold required to demonstrate efficacy.
Percentage of Participants Achieving a Major Cytogenetic Response by Subpopulation and Total Population
Subpopulations reflect chronic myeloid leukemia (CML) phases at the time of enrollment: chronic, accelerated, and blast phase. Primary endpoints as adjudicated by the Data Monitoring Committee were used for the primary analyses.
Major cytogenetic response includes complete or partial response. Both confirmed and unconfirmed major cytogenetic response is considered meaningful. Unconfirmed response is based on a single bone marrow cytogenetic evaluation for participants where a confirmatory evaluation is not available.
Complete response shows 0% Philadelphia chromosome positive (Ph+) cells. A partial response shows >0% - 35% Ph+ cells.
Response rates by disease phase were examined relative to an a priori value of 2.5% using a one-sided lower 95% exact binomial confidence limit. If the lower limit from the one-sided lower 95% confidence limit exceeds 2.5%, the observed response rate will have exceeded the minimum threshold required to demonstrate efficacy.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Subpopulation and Total
TEAE are any untoward events that were newly occurring or worsening from Baseline.
Treatment related toxicity was considered by the investigator to be unrelated, possibly, probably or unknown related to study drug. Severity was graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v3.0 on the following scale: Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = life-threatening, Grade 5 = death. A serious adverse event (SAE) is any untoward medical occurrence that is fatal or life-threatening; results in persistent or significant disability or incapacity; requires or prolongs in-patient hospitalization; is a congenital anomaly/birth defect in the offspring of a patient; and conditions not included in the above that may jeopardize the patient or may require intervention to prevent one of the outcomes listed above.
A participant is only counted once in each category (at worst severity or strongest relationship).
Secondary Outcome Measures
Percentage of Participants in Each Cytogenetic Response Category Representing the Degree of Suppression of the Philadelphia Chromosome (Ph+)
Cytogenetic response categories:
Complete: 0% Ph+ cells
Partial: >0%-35% Ph+ cells
Minor: >35%-65% Ph+ cells
Minimal: >65%-95% Ph+ cells
No Response: >95% Ph+ cells
Unevaluable: <20 metaphases were examined and/or response could not be assigned
Percentage of Participants With Major Molecular Response (MMR) Representing the Degree of Suppression of BCR-ABL Transcript Levels Using the Housekeeping Gene GUS
MMR is defined as a ratio of BCR-ABL/standard gene of less than 0.1% according to the international scale. BCR-ABL is a fusion gene of the breakpoint cluster region [BCR] gene and Abelson proto-oncogene [ABL] genes). This analysis used the standard gene GUS. Analysis was performed by quantitative reverse transcription polymerase chain reaction (qRT-PCR) of peripheral blood.
Percentage of Participants With Major Molecular Response (MMR) Representing the Degree of Suppression of BCR-ABL Transcript Levels Using the Housekeeping Gene ABL
MMR is defined as a ratio of BCR-ABL/standard gene of less than 0.1% according to the international scale. BCR-ABL is a fusion gene of the breakpoint cluster region [BCR] gene and Abelson proto-oncogene [ABL] genes). This analysis used the standard gene ABL. Analysis was performed by quantitative reverse transcription polymerase chain reaction (qRT-PCR) of peripheral blood.
Percentage of Participants in Each Hematologic Response Category
Complete Response (CHR)
Chronic phase must last at least 8 weeks: WBC <10*10^9/liter, platelets <450*10^9/liter, myelocytes + metamyelocytes <5% in blood, no blasts or promyelocytes in blood, <20% basophils in peripheral blood, no extramedullary involvement.
Accelerated and Blast phase must last at least 4 weeks: absolute neutrophil count 1.5*10^9/liter, platelets 100*10^9/liter, no blood blasts, bone marrow blasts <5%, no extramedullary disease.
Partial Response - CHR plus one or more of the following:
Persistence of splenomegaly with a reduction of ≥50% from pre-treatment
Platelets > 450*10^9/L
Presence of immature cells in the peripheral blood
5% to 25% blasts in the bone marrow
If extra-medullary disease pre-treatment, reduction by ≥50% Hematologic Improvement - CHR, except allowing persistent thrombocytopenia (<100*10^9/L), and a few immature cells No evidence of leukemia: Morphologic leukemia-free state, defined as <5% bone marrow blasts.
Percentage of Participants With Extramedullary Disease (EMD) at Baseline Achieving a Clinical Response
Clinical response was defined by disease phase and based on evaluations by the independent Data Monitoring Committee (DMC).
Chronic Phase subgroup: achieving a complete hematologic response and/or major cytogenetic response (complete cytogenetic response or partial cytogenetic response, confirmed or unconfirmed).
Accelerated Phase and Blast Phase subgroups: achieving complete hematologic response, no evidence of leukemia, return to chronic phase, and/or major cytogenetic response (complete cytogenetic response or partial cytogenetic response, confirmed or unconfirmed).
Percentage of Participants With the Largest Percentage Reduction From Baseline of T315I Mutated BCR-ABL
Summarization is based on the best of the individual response assessments. Not assessable indicates that the participant either had no baseline assessment or the % mutation could not be determined in the post-baseline assessment(s).
Number of Treatment Cycles Needed to Achieve Best Hematologic Response
Induction therapy was administered for 14 consecutive days for each 28 days cycle, for up to 6 cycles. All treatment arms were given omacetaxine mepesuccinate via subcutaneous (SC) administration at 1.25 mg/m^2 twice a day (BID) for the 14 consecutive days.
Number of Treatment Cycles Needed to Achieve Best Cytogenetic Response
Kaplan-Meier Estimates for Time to Onset of Best Hematologic Response
Time to onset was analyzed using Kaplan-Meier estimates. Participants who did not achieve a response are censored at their last visit day.
Overall hematologic response for chronic phase participants includes confirmed complete hematologic response (CHR). Overall hematologic response for accelerated or blast phase participants includes confirmed complete hematologic response (CHR), no evidence of leukemia (NEL), or return to chronic phase (RCP). Hematologic response must last >= 8 weeks to be considered meaningful.
Kaplan-Meier Estimates for Time to Onset of Best Cytogenetic Response
Time to onset was analyzed using Kaplan-Meier estimates. Participants who did not achieve a response are censored at their last visit day.
Major cytogenetic response includes complete or partial response. Both confirmed and unconfirmed major cytogenetic response is considered meaningful. Unconfirmed response is based on a single bone marrow cytogenetic evaluation for participants where a confirmatory evaluation is not available.
Complete response shows 0% Philadelphia chromosome positive (Ph+) cells. A partial response shows >0% - 35% Ph+ cells.
Kaplan-Meier Estimates for Duration of Best Hematologic Response
Duration of response is defined as the time from first reported date of hematologic response until the earliest date of objective evidence of disease progression, relapse or death. Data was censored at the last examination date for participants with ongoing response or participants who discontinued treatment for reasons other than adverse event, disease progression or death.
Kaplan-Meier Estimates for Duration of Best Cytogenetic Response
Duration of response is defined as the time from first reported date of cytogenetic response until the earliest date of objective evidence of disease progression, relapse or death. Data was censored at the last examination date for participants with ongoing response or participants who discontinued treatment for reasons other than adverse event, disease progression or death.
Kaplan-Meier Estimates for Time to Disease Progression
Time to disease progression is defined as the time from the initiation of treatment until the onset date of death, the development of CML accelerated phase or blast phase, or the loss of complete hematologic response or major cytogenetic response, whichever came first. Participants were censored only if they did not have progression or if they discontinued treatment for reasons other than AE, progression or death.
Kaplan-Meier Estimates for Overall Survival
Overall survival is defined as the time from the initiation of treatment until death from any cause or the last day of participant contact or evaluation for participants that were lost to follow-up. Participants were censored t the last recorded contract or evaluation when a participant was alive at time of analysis. A quarterly phone survey was conducted to collect survival data for participants who discontinued from the study.
Full Information
NCT ID
NCT00462943
First Posted
April 17, 2007
Last Updated
December 1, 2021
Sponsor
Teva Branded Pharmaceutical Products R&D, Inc.
Collaborators
Cephalon, ChemGenex Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT00462943
Brief Title
Open Label Study of Subcutaneous Homoharringtonine (Omacetaxine Mepesuccinate) in Patients With Advanced CML
Official Title
A Phase II Open-Label Study of the Subcutaneous Administration of Homoharringtonine. (Omacetaxine Mepesuccinate; OMA) in the Treatment of Patients With Chronic Myeloid. Leukemia (CML) Who Have Failed or Are Intolerant to Tyrosine Kinase Inhibitor Therapy
Study Type
Interventional
2. Study Status
Record Verification Date
December 2021
Overall Recruitment Status
Completed
Study Start Date
March 7, 2007 (Actual)
Primary Completion Date
August 4, 2009 (Actual)
Study Completion Date
June 27, 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Teva Branded Pharmaceutical Products R&D, Inc.
Collaborators
Cephalon, ChemGenex Pharmaceuticals
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
A Phase II open-label trial of subcutaneous HHT (omacetaxine mepesuccinate) in the treatment of patients who are resistant to or intolerant to Tyrosine Kinase Inhibitors.
Detailed Description
This will be an open label, multicenter study of subcutaneous HHT (omacetaxine mepesuccinate) therapy of patients with chronic myeloid leukemia (CML) in chronic, accelerated, or blast phase who have failed or are intolerant to tyrosine kinase inhibitor therapy. Patients will be treated with induction course cycles consisting of subcutaneous (SC) HHT 1.25 mg/m² twice daily for 14 consecutive days every 28 days. Patients will be evaluated every 7 days with complete blood and platelet counts while undergoing induction therapy; the number of consecutive doses of HHT or intervals between subsequent cycles may be adjusted, as clinically indicated, according to guidelines provided in the treatment plan.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Myeloid Leukemia
Keywords
CML, HHT, Homoharringtonine, Omacetaxine
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
100 (Actual)
8. Arms, Groups, and Interventions
Arm Title
OMA
Arm Type
Experimental
Arm Description
Omacetaxine mepesuccinate (OMA) Induction: 1.25mg/m^2 subcutaneously twice daily for 14 consecutive days, every 28 days for up to six cycles.
Omacetaxine mepesuccinate (OMA) Maintenance: 1.25mg/m^2 subcutaneously twice daily for 7 consecutive days, every 28 days for up to 24 months.
Intervention Type
Drug
Intervention Name(s)
Omacetaxine mepesuccinate
Other Intervention Name(s)
Homoharringtonine, HHT, Synribo, OMA, CGX-635
Intervention Description
Induction: 1.25mg/m^2 subcutaneously twice daily for 14 consecutive days, every 28 days.
Maintenance: 1.25mg/m^2 subcutaneously twice daily for 7 consecutive days, every 28 days.
Response targets during induction vary by chronic myeloid leukemia (CML) subclass (chronic, accelerated, or blast phase). Participants will complete at least one cycle (14 days treatment of a 28 day cycle) of induction therapy before changing to maintenance therapy. Participants not demonstrating evidence of clinical response after 6 induction cycles will be considered for removal from the study.
Primary Outcome Measure Information:
Title
Percentage of Participants Achieving an Overall Hematologic Response by Subpopulation and Total Population
Description
Subpopulations reflect chronic myeloid leukemia (CML) phases at the time of enrollment: chronic, accelerated, and blast phase. Primary endpoints as adjudicated by the Data Monitoring Committee were used for the primary analyses.
Overall hematologic response for chronic phase participants includes confirmed complete hematologic response (CHR). Overall hematologic response for accelerated or blast phase participants includes confirmed complete hematologic response (CHR), no evidence of leukemia (NEL), or return to chronic phase (RCP). Hematologic response must last >= 8 weeks to be considered meaningful.
Response rates by disease phase were examined relative to an a priori value of 2.5% using a one-sided lower 95% exact binomial confidence limit. If the lower limit from the one-sided lower 95% confidence limit exceeds 2.5%, the observed response rate will have exceeded the minimum threshold required to demonstrate efficacy.
Time Frame
Day 1 up to 6 months
Title
Percentage of Participants Achieving a Major Cytogenetic Response by Subpopulation and Total Population
Description
Subpopulations reflect chronic myeloid leukemia (CML) phases at the time of enrollment: chronic, accelerated, and blast phase. Primary endpoints as adjudicated by the Data Monitoring Committee were used for the primary analyses.
Major cytogenetic response includes complete or partial response. Both confirmed and unconfirmed major cytogenetic response is considered meaningful. Unconfirmed response is based on a single bone marrow cytogenetic evaluation for participants where a confirmatory evaluation is not available.
Complete response shows 0% Philadelphia chromosome positive (Ph+) cells. A partial response shows >0% - 35% Ph+ cells.
Response rates by disease phase were examined relative to an a priori value of 2.5% using a one-sided lower 95% exact binomial confidence limit. If the lower limit from the one-sided lower 95% confidence limit exceeds 2.5%, the observed response rate will have exceeded the minimum threshold required to demonstrate efficacy.
Time Frame
Day 1 up to 9 months
Title
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Subpopulation and Total
Description
TEAE are any untoward events that were newly occurring or worsening from Baseline.
Treatment related toxicity was considered by the investigator to be unrelated, possibly, probably or unknown related to study drug. Severity was graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v3.0 on the following scale: Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = life-threatening, Grade 5 = death. A serious adverse event (SAE) is any untoward medical occurrence that is fatal or life-threatening; results in persistent or significant disability or incapacity; requires or prolongs in-patient hospitalization; is a congenital anomaly/birth defect in the offspring of a patient; and conditions not included in the above that may jeopardize the patient or may require intervention to prevent one of the outcomes listed above.
A participant is only counted once in each category (at worst severity or strongest relationship).
Time Frame
up to 4 years
Secondary Outcome Measure Information:
Title
Percentage of Participants in Each Cytogenetic Response Category Representing the Degree of Suppression of the Philadelphia Chromosome (Ph+)
Description
Cytogenetic response categories:
Complete: 0% Ph+ cells
Partial: >0%-35% Ph+ cells
Minor: >35%-65% Ph+ cells
Minimal: >65%-95% Ph+ cells
No Response: >95% Ph+ cells
Unevaluable: <20 metaphases were examined and/or response could not be assigned
Time Frame
Day 1 up to Month 9
Title
Percentage of Participants With Major Molecular Response (MMR) Representing the Degree of Suppression of BCR-ABL Transcript Levels Using the Housekeeping Gene GUS
Description
MMR is defined as a ratio of BCR-ABL/standard gene of less than 0.1% according to the international scale. BCR-ABL is a fusion gene of the breakpoint cluster region [BCR] gene and Abelson proto-oncogene [ABL] genes). This analysis used the standard gene GUS. Analysis was performed by quantitative reverse transcription polymerase chain reaction (qRT-PCR) of peripheral blood.
Time Frame
Day 1 up to Month 6
Title
Percentage of Participants With Major Molecular Response (MMR) Representing the Degree of Suppression of BCR-ABL Transcript Levels Using the Housekeeping Gene ABL
Description
MMR is defined as a ratio of BCR-ABL/standard gene of less than 0.1% according to the international scale. BCR-ABL is a fusion gene of the breakpoint cluster region [BCR] gene and Abelson proto-oncogene [ABL] genes). This analysis used the standard gene ABL. Analysis was performed by quantitative reverse transcription polymerase chain reaction (qRT-PCR) of peripheral blood.
Time Frame
Day 1 up to Month 6
Title
Percentage of Participants in Each Hematologic Response Category
Description
Complete Response (CHR)
Chronic phase must last at least 8 weeks: WBC <10*10^9/liter, platelets <450*10^9/liter, myelocytes + metamyelocytes <5% in blood, no blasts or promyelocytes in blood, <20% basophils in peripheral blood, no extramedullary involvement.
Accelerated and Blast phase must last at least 4 weeks: absolute neutrophil count 1.5*10^9/liter, platelets 100*10^9/liter, no blood blasts, bone marrow blasts <5%, no extramedullary disease.
Partial Response - CHR plus one or more of the following:
Persistence of splenomegaly with a reduction of ≥50% from pre-treatment
Platelets > 450*10^9/L
Presence of immature cells in the peripheral blood
5% to 25% blasts in the bone marrow
If extra-medullary disease pre-treatment, reduction by ≥50% Hematologic Improvement - CHR, except allowing persistent thrombocytopenia (<100*10^9/L), and a few immature cells No evidence of leukemia: Morphologic leukemia-free state, defined as <5% bone marrow blasts.
Time Frame
Day 1 up to Month 6
Title
Percentage of Participants With Extramedullary Disease (EMD) at Baseline Achieving a Clinical Response
Description
Clinical response was defined by disease phase and based on evaluations by the independent Data Monitoring Committee (DMC).
Chronic Phase subgroup: achieving a complete hematologic response and/or major cytogenetic response (complete cytogenetic response or partial cytogenetic response, confirmed or unconfirmed).
Accelerated Phase and Blast Phase subgroups: achieving complete hematologic response, no evidence of leukemia, return to chronic phase, and/or major cytogenetic response (complete cytogenetic response or partial cytogenetic response, confirmed or unconfirmed).
Time Frame
Day 1 up to Month 9
Title
Percentage of Participants With the Largest Percentage Reduction From Baseline of T315I Mutated BCR-ABL
Description
Summarization is based on the best of the individual response assessments. Not assessable indicates that the participant either had no baseline assessment or the % mutation could not be determined in the post-baseline assessment(s).
Time Frame
Day 1 up to Month 9
Title
Number of Treatment Cycles Needed to Achieve Best Hematologic Response
Description
Induction therapy was administered for 14 consecutive days for each 28 days cycle, for up to 6 cycles. All treatment arms were given omacetaxine mepesuccinate via subcutaneous (SC) administration at 1.25 mg/m^2 twice a day (BID) for the 14 consecutive days.
Time Frame
Day 1 up to Month 6
Title
Number of Treatment Cycles Needed to Achieve Best Cytogenetic Response
Time Frame
Day 1 up to Month 9
Title
Kaplan-Meier Estimates for Time to Onset of Best Hematologic Response
Description
Time to onset was analyzed using Kaplan-Meier estimates. Participants who did not achieve a response are censored at their last visit day.
Overall hematologic response for chronic phase participants includes confirmed complete hematologic response (CHR). Overall hematologic response for accelerated or blast phase participants includes confirmed complete hematologic response (CHR), no evidence of leukemia (NEL), or return to chronic phase (RCP). Hematologic response must last >= 8 weeks to be considered meaningful.
Time Frame
Day 1 up to Month 6
Title
Kaplan-Meier Estimates for Time to Onset of Best Cytogenetic Response
Description
Time to onset was analyzed using Kaplan-Meier estimates. Participants who did not achieve a response are censored at their last visit day.
Major cytogenetic response includes complete or partial response. Both confirmed and unconfirmed major cytogenetic response is considered meaningful. Unconfirmed response is based on a single bone marrow cytogenetic evaluation for participants where a confirmatory evaluation is not available.
Complete response shows 0% Philadelphia chromosome positive (Ph+) cells. A partial response shows >0% - 35% Ph+ cells.
Time Frame
Day 1 up to Month 9
Title
Kaplan-Meier Estimates for Duration of Best Hematologic Response
Description
Duration of response is defined as the time from first reported date of hematologic response until the earliest date of objective evidence of disease progression, relapse or death. Data was censored at the last examination date for participants with ongoing response or participants who discontinued treatment for reasons other than adverse event, disease progression or death.
Time Frame
up to four years
Title
Kaplan-Meier Estimates for Duration of Best Cytogenetic Response
Description
Duration of response is defined as the time from first reported date of cytogenetic response until the earliest date of objective evidence of disease progression, relapse or death. Data was censored at the last examination date for participants with ongoing response or participants who discontinued treatment for reasons other than adverse event, disease progression or death.
Time Frame
up to four years
Title
Kaplan-Meier Estimates for Time to Disease Progression
Description
Time to disease progression is defined as the time from the initiation of treatment until the onset date of death, the development of CML accelerated phase or blast phase, or the loss of complete hematologic response or major cytogenetic response, whichever came first. Participants were censored only if they did not have progression or if they discontinued treatment for reasons other than AE, progression or death.
Time Frame
up to 4 years
Title
Kaplan-Meier Estimates for Overall Survival
Description
Overall survival is defined as the time from the initiation of treatment until death from any cause or the last day of participant contact or evaluation for participants that were lost to follow-up. Participants were censored t the last recorded contract or evaluation when a participant was alive at time of analysis. A quarterly phone survey was conducted to collect survival data for participants who discontinued from the study.
Time Frame
up to 4 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Male or female patients, age 18 years or older
Philadelphia chromosome (Ph) positive chronic myelogenous leukemia in either chronic, accelerated, or blast phase
Patients will have either failed, demonstrated intolerance, or a combination of prior failure and intolerance, to prior treatments with at least two tyrosine kinase inhibitors (TKI's). Failure of TKI treatment may either be primary (never achieved a response) or secondary resistance (loss of response).
Acceptable Renal and Liver Function
Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
Sexually active patients and their partners must use an effective double barrier method of contraception
Exclusion Criteria:
New York Heart Association classification (NYHA) class III or IV heart disease, active ischemia or any other uncontrolled cardiac condition
Myocardial infarction in the previous 12 weeks.
Other concurrent illness which would preclude study conduct and assessment
uncontrolled and active infection, and positive HIV or positive HTLV I/II status, whether on treatment or not.
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.
Lymphoid Ph+ blast crisis
Patient is enrolled in another clinical investigation within 30 days of enrollment or is receiving another investigational agent
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jorge Cortes, MD
Organizational Affiliation
M.D. Anderson Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Teva Investigational Site 303
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Facility Name
Teva Investigational Site 308
City
Beech Grove
State/Province
Indiana
ZIP/Postal Code
46107
Country
United States
Facility Name
Teva Investigational Site 311
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Facility Name
Teva Investigational Site 302
City
Bronx
State/Province
New York
ZIP/Postal Code
10466
Country
United States
Facility Name
Teva Investigational Site 305
City
Buffalo
State/Province
New York
ZIP/Postal Code
14263
Country
United States
Facility Name
Teva Investigational Site 310
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19111
Country
United States
Facility Name
Teva Investigational Site 301
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Teva Investigational Site 314
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States
Facility Name
Teva Investigational Site 313
City
Montreal
ZIP/Postal Code
H3a 1a1
Country
Canada
Facility Name
Teva Investigational Site 309
City
Toronto
ZIP/Postal Code
M5G 2M9
Country
Canada
Facility Name
Teva Investigational Site 329
City
Bordeaux
ZIP/Postal Code
33076
Country
France
Facility Name
Teva Investigational Site 321
City
Le Chesnay Cedex
ZIP/Postal Code
78157
Country
France
Facility Name
Teva Investigational Site 322
City
Lille
ZIP/Postal Code
59000
Country
France
Facility Name
Teva Investigational Site 320
City
Lyon Cedex 03
ZIP/Postal Code
69437
Country
France
Facility Name
Teva Investigational Site 324
City
Nice
ZIP/Postal Code
06202
Country
France
Facility Name
Teva Investigational Site 328
City
Paris
ZIP/Postal Code
75475
Country
France
Facility Name
Teva Investigational Site 323
City
Poitiers Cedex
ZIP/Postal Code
86021
Country
France
Facility Name
Teva Investigational Site 327
City
Strasbourg
ZIP/Postal Code
67100
Country
France
Facility Name
Teva Investigational Site 325
City
Toulouse
ZIP/Postal Code
31059
Country
France
Facility Name
Teva Investigational Site 331
City
Berlin
ZIP/Postal Code
10117
Country
Germany
Facility Name
Teva Investigational Site 330
City
Mannheim
ZIP/Postal Code
68169
Country
Germany
Facility Name
Teva Investigational Site 350
City
Budapest
ZIP/Postal Code
1096
Country
Hungary
Facility Name
Teva Investigational Site 371
City
Hyderabad
ZIP/Postal Code
500082
Country
India
Facility Name
Teva Investigational Site 370
City
Mumbai
ZIP/Postal Code
400 014
Country
India
Facility Name
Teva Investigational Site 390
City
Bologna
ZIP/Postal Code
41038
Country
Italy
Facility Name
Teva Investigational Site 360
City
Gdansk
ZIP/Postal Code
80-952
Country
Poland
Facility Name
Teva Investigational Site 361
City
Warszawa
ZIP/Postal Code
02776
Country
Poland
Facility Name
Teva Investigational Site 380
City
Singapore
ZIP/Postal Code
169608
Country
Singapore
Facility Name
Teva Investigational Site 340
City
London
ZIP/Postal Code
W12 0HS
Country
United Kingdom
12. IPD Sharing Statement
Citations:
PubMed Identifier
23468307
Citation
Cortes J, Digumarti R, Parikh PM, Wetzler M, Lipton JH, Hochhaus A, Craig AR, Benichou AC, Nicolini FE, Kantarjian HM; Omacetaxine 203 Study Group. Phase 2 study of subcutaneous omacetaxine mepesuccinate for chronic-phase chronic myeloid leukemia patients resistant to or intolerant of tyrosine kinase inhibitors. Am J Hematol. 2013 May;88(5):350-4. doi: 10.1002/ajh.23408. Epub 2013 Mar 7.
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Open Label Study of Subcutaneous Homoharringtonine (Omacetaxine Mepesuccinate) in Patients With Advanced CML
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