Chronic Myeloid LeukemiaPhase 2NCT00375219
Homoharringtonine (Omacetaxine Mepesuccinate) in Treating Patients With Chronic Myeloid Leukemia (CML) With the T315I BCR-ABL Gene Mutation
A Phase 2 study testing Omacetaxine mepesuccinate in people with Chronic Myeloid Leukemia, run by Teva Branded Pharmaceutical Products R&D, Inc. at 32 sites in 10 countries.
Trial summary
To evaluate the safety and efficacy of subcutaneous administration of omacetaxine mepesuccinate (HHT) in achieving a clinical response in CML patients in chronic, accelerated, or blast phase who have failed prior imatinib therapy and have the T315I kinase domain gene mutation. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Myeloid Leukemia
- What is being tested?
- Omacetaxine mepesuccinate
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 103 participants
- Where
- 32 sitesin 10 countries
- Study dates
- 20 Sep 2006to 28 Jun 2013
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female patients, age 18 years or older
- Philadelphia chromosome (Ph) positive chronic myelogenous leukemia in either chronic, accelerated, or blast phase
- The patient will have the T315I BCR-ABL gene mutation
- Patients will have failed prior imatinib therapy
- ECOG performance status 0-2
Who cannot join
- 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
- Lymphoid Ph+ blast crisis
Trial locations and contacts
32 sites in 10 countries.
32 sites in 10 countries
United States10 sites
Teva Investigational Site 006
Atlanta, Georgia, 30329
Teva Investigational Site 011
Baltimore, Maryland, 21201
Teva Investigational Site 008
Beech Grove, Indiana, 46107
Teva Investigational Site 004
Boston, Massachusetts, 02111
Teva Investigational Site 005
Buffalo, New York, 14263
Teva Investigational Site 001
Houston, Texas, 77030
Teva Investigational Site 007
Jacksonville, Florida, 32224
Teva Investigational Site 003
Los Angeles, California, 90033
Teva Investigational Site 010
Philadelphia, Pennsylvania, 19111
Teva Investigational Site 002
The Bronx, New York, 10467
France10 sites
Teva Investigational Site 029
Bordeaux, 33076
Teva Investigational Site 021
Le Chesnay, 78157
Teva Investigational Site 022
Lille, 59000
Teva Investigational Site 020
Lyon, 69437
Teva Investigational Site 024
Nice, 06202
Teva Investigational Site 028
Paris, 75475
Teva Investigational Site 023
Poitiers, 86021
Teva Investigational Site 027
Strasbourg, 67100
Teva Investigational Site 025
Toulouse, 31059
Teva Investigational Site 026
Vandœuvre-lès-Nancy, 54511
Canada2 sites
Teva Investigational Site 013
Montreal, H3a 1a1
Teva Investigational Site 009
Toronto, M5G 2M9
Germany2 sites
Teva Investigational Site 031
Berlin, 10117
Teva Investigational Site 030
Mannheim, 68169
India2 sites
Teva Investigational Site 071
Hyderabad, 500082
Teva Investigational Site 070
Mumbai, 400 014
Poland2 sites
Teva Investigational Site 060
Gdansk, 80-952
Teva Investigational Site 061
Warsaw, 02776
About this study
Official title: A Phase II Open-Label Study of the Subcutaneous Administration of Homoharringtonine. (Omacetaxine) (CGX-635) in the Treatment of Patients With Chronic Myeloid Leukemia. (CML) With the T315I BCR-ABL Gene Mutation
To evaluate the safety and efficacy of subcutaneous administration of omacetaxine mepesuccinate (HHT) in achieving a clinical response in CML patients in chronic, accelerated, or blast phase who have failed prior imatinib therapy and have the T315I kinase domain gene mutation.
Read the detailed description
Point mutations within the ABL kinase domain of the BCR-ABL gene are emerging as the most frequent mechanism for resistance to imatinib and resultant reactivation of kinase activity. The risk of mutation development is particularly high in patients who are beyond chronic phase, as well as those with a long duration of disease prior to imatinib therapy.
The T315I kinase domain (KD) point mutation has merited particular attention, as T315I expressing CML cells are markedly resistant to imatinib. CML patients with the T315I KD mutation, therefore, do not respond to continued treatment with imatinib, and preliminary clinical data indicate that neither of two newer tyrosine kinase inhibitors will have activity in patients with T315I KD mutation either.
Omacetaxine mepesuccinate (HHT) is a potent inducer of apoptosis (programmed cell death) in myeloid cells and inhibits angiogenesis (blood vessel formation). In Phase 2 studies, HHT has demonstrated clinical activity in patients with CML, both as a single agent and in-combination with other chemotherapeutic drugs. HHT works via a different mechanism than imatinib or other tyrosine kinase inhibitors (TKI's), and HHT has been shown to inhibit in vitro CML cell lines which harbor the T315I KD mutation and are highly resistant to imatinib. Therefore, CML patients who have the T315I KD mutation may still respond to treatment with HHT. HHT may therefore be an attractive therapeutic option for patients with the T315I KD mutation.
On this basis, a multicenter clinical trial is being conducted of HHT therapy for CML patients who have failed prior imatinib therapy and have the T315I KD mutation.
Patients will be treated with an induction course consisting of subcutaneous (SC) HHT twice daily for 14 consecutive days every 28 days. Patients who demonstrate a response, may receive maintenance therapy for up to 24 months, consisting of subcutaneous (SC) HHT twice daily for 7 days every 28 days.
- Conditions
- Chronic Myeloid Leukemia
- Being tested
- Omacetaxine mepesuccinate
- Keywords
- Chronic Myeloid Leukemia, CML, HHT, Homoharringtonine, Omacetaxine, T315i, ChemGenex, ChemGenex Pharmaceuticals
- Medical subject headings
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Omacetaxine mepesuccinateDrug
Also called Homoharringtonine, OMA, Synribo, HHT
Induction:
1.25 mg/m^2 subcutaneously, twice daily for 14 consecutive days every 28 days until response. Patients not demonstrating evidence of clinical response after 6 induction cycles will be considered for removal from the study.
Maintenance:
1.25 mg/m^2 subcutaneously, twice daily for 7 consecutive days in a 28-day cycle, for up to 3 years.
| Study group | Role | What they receive |
|---|---|---|
| omacetaxine | Experimental | Treatment was the same for all cohorts: induction therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 14 consecutive days every 28 (±3) days for up to 6 cycles. Maintenance therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 7 consecutive days every 28 (±3) days for up to 3 years. Receives: Drug: Omacetaxine mepesuccinate |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Day 1 up to 6 months
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.
Measured: Day 1 up to 6 months
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).
Measured: up to 3 years
Secondary outcomes (14)
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
Measured: Day 1 up to Month 9
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.
Measured: Day 1 up to Month 6
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.
Measured: Day 1 up to Month 6
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.
Measured: Day 1 up to Month 6
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).
The percentage of participants achieving response with extramedullary disease at Baseline was to be summarized, if the sample size was sufficient. This analysis was not done as the sample was ultimately insufficient
Measured: Day 1 up to Month 9
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).
Measured: Day 1 up to Month 9
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.
Measured: Day 1 up to Month 6
Number of Treatment Cycles Needed to Achieve Best Cytogenetic Response
Measured: Day 1 up to 22 months
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.
Measured: Day 1 up to Month 6
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.
Measured: up to 3 years
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.
Measured: up to 4 years
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.
Measured: up to 4 years
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.
Measured: up to 4 years
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.
Measured: up to 4 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Sep 2006 (estimated)
- Study start20 Sep 2006
- Primary completion23 Mar 2010
- Study completion28 Jun 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Chronic Myeloid LeukemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 103 participants (actual)
Sponsor and investigators
- Lead sponsor
- Teva Branded Pharmaceutical Products R&D, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Cephalon, ChemGenex Pharmaceuticals
- Responsible party
- Sponsor
- Investigators
- Jorge Cortes, MD, Principal investigator, Univ. of Texas M.D. Anderson Cancer CenterAndreas Hochhaus, MD Prof Dr, Principal investigator, Mannheim der Universitat Heidelberg
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00375219
- Sponsor's protocol ID
- CGX-635-CML-202
- Other IDs
- 2006-000176-32
- Status last verified
- Nov 2021
- First submitted
- 8 Sep 2006
- Last updated
- 15 Nov 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Cortes J, Lipton JH, Rea D, Digumarti R, Chuah C, Nanda N, Benichou AC, Craig AR, Michallet M, Nicolini FE, Kantarjian H; Omacetaxine 202 Study Group. Phase 2 study of subcutaneous omacetaxine mepesuccinate after TKI failure in patients with chronic-phase CML with T315I mutation. Blood. 2012 Sep 27;120(13):2573-80. doi: 10.1182/blood-2012-03-415307. Epub 2012 Aug 15.
PubMed 22896000
Study at a glance
From the registry record, last updated by the sponsor on 15 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Open-Label Study of the Subcutaneous Administration of Homoharringtonine. (Omacetaxine) (CGX-635) in the Treatment of Patients With Chronic Myeloid Leukemia. (CML) With the T315I BCR-ABL Gene Mutation
- ClinicalTrials.gov ID
- NCT00375219
- Acronym / sponsor ID
- CGX-635-CML-202
- Conditions
- Chronic Myeloid Leukemia
- Keywords
- Chronic Myeloid Leukemia, CML, HHT, Homoharringtonine, Omacetaxine, T315i, ChemGenex, ChemGenex Pharmaceuticals
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 103 participants (actual)
- Lead sponsor
- Teva Branded Pharmaceutical Products R&D, Inc.Industry (pharma, biotech, devices)
- Collaborators
- Cephalon, ChemGenex Pharmaceuticals
- Study start
- 20 Sep 2006 (actual)
- Primary completion
- 23 Mar 2010 (actual)
- Study completion
- 28 Jun 2013 (actual)
- First posted
- 12 Sep 2006 (estimated)
- Results
- Posted 3 Jun 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To evaluate the safety and efficacy of subcutaneous administration of omacetaxine mepesuccinate (HHT) in achieving a clinical response in CML patients in chronic, accelerated, or blast phase who have failed prior imatinib therapy and have the T315I kinase domain gene mutation.
Detailed description
Point mutations within the ABL kinase domain of the BCR-ABL gene are emerging as the most frequent mechanism for resistance to imatinib and resultant reactivation of kinase activity. The risk of mutation development is particularly high in patients who are beyond chronic phase, as well as those with a long duration of disease prior to imatinib therapy.
The T315I kinase domain (KD) point mutation has merited particular attention, as T315I expressing CML cells are markedly resistant to imatinib. CML patients with the T315I KD mutation, therefore, do not respond to continued treatment with imatinib, and preliminary clinical data indicate that neither of two newer tyrosine kinase inhibitors will have activity in patients with T315I KD mutation either.
Omacetaxine mepesuccinate (HHT) is a potent inducer of apoptosis (programmed cell death) in myeloid cells and inhibits angiogenesis (blood vessel formation). In Phase 2 studies, HHT has demonstrated clinical activity in patients with CML, both as a single agent and in-combination with other chemotherapeutic drugs. HHT works via a different mechanism than imatinib or other tyrosine kinase inhibitors (TKI's), and HHT has been shown to inhibit in vitro CML cell lines which harbor the T315I KD mutation and are highly resistant to imatinib. Therefore, CML patients who have the T315I KD mutation may still respond to treatment with HHT. HHT may therefore be an attractive therapeutic option for patients with the T315I KD mutation.
On this basis, a multicenter clinical trial is being conducted of HHT therapy for CML patients who have failed prior imatinib therapy and have the T315I KD mutation.
Patients will be treated with an induction course consisting of subcutaneous (SC) HHT twice daily for 14 consecutive days every 28 days. Patients who demonstrate a response, may receive maintenance therapy for up to 24 months, consisting of subcutaneous (SC) HHT twice daily for 7 days every 28 days.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| omacetaxine | Experimental | Drug: Omacetaxine mepesuccinateTreatment was the same for all cohorts: induction therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 14 consecutive days every 28 (±3) days for up to 6 cycles. Maintenance therapy was subcutaneous (SC) administration of omacetaxine at 1.25 mg/m^2 twice a day (BID), administered for 7 consecutive days every 28 (±3) days for up to 3 years. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Male or female patients, age 18 years or older
- Philadelphia chromosome (Ph) positive chronic myelogenous leukemia in either chronic, accelerated, or blast phase
- The patient will have the T315I BCR-ABL gene mutation
- Patients will have failed prior imatinib therapy
- ECOG performance status 0-2
Key exclusion criteria (3 listed)
- 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
- Lymphoid Ph+ blast crisis
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Omacetaxine mepesuccinateAlso: Homoharringtonine, OMA, Synribo, HHTInduction: 1.25 mg/m^2 subcutaneously, twice daily for 14 consecutive days every 28 days until response. Patients not demonstrating evidence of clinical response after 6 induction cycles will be considered for removal from the study. Maintenance: 1.25 mg/m^2 subcutaneously, twice daily for 7 consecutive days in a 28-day cycle, for up to 3 years. | Drug | omacetaxine |
Primary outcome
Percentage of Participants Achieving an Overall Hematologic Response by Subpopulation and Total Population
Time frame: Day 1 up to 6 months
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
Time frame: Day 1 up to 6 months
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
Time frame: up to 3 years
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).
14 secondary outcomes
Percentage of Participants in Each Cytogenetic Response Category Representing the Degree of Suppression of the Philadelphia Chromosome (Ph+)
Time frame: Day 1 up to Month 9
Percentage of Participants With Major Molecular Response (MMR) Representing the Degree of Suppression of BCR-ABL Transcript Levels Using the Housekeeping Gene GUS
Time frame: Day 1 up to Month 6
Percentage of Participants With Major Molecular Response (MMR) Representing the Degree of Suppression of BCR-ABL Transcript Levels Using the Housekeeping Gene ABL
Time frame: Day 1 up to Month 6
Percentage of Participants in Each Hematologic Response Category
Time frame: Day 1 up to Month 6
Percentage of Participants With Extramedullary Disease (EMD) at Baseline Achieving a Clinical Response
Time frame: Day 1 up to Month 9
Percentage of Participants With the Largest Percentage Reduction From Baseline of T315I Mutated BCR-ABL
Time frame: Day 1 up to Month 9
Number of Treatment Cycles Needed to Achieve Best Hematologic Response
Time frame: Day 1 up to Month 6
Number of Treatment Cycles Needed to Achieve Best Cytogenetic Response
Time frame: Day 1 up to 22 months
Kaplan-Meier Estimates for Time to Onset of Best Hematologic Response
Time frame: Day 1 up to Month 6
Kaplan-Meier Estimates for Time to Onset of Best Cytogenetic Response
Time frame: up to 3 years
Kaplan-Meier Estimates for Duration of Best Hematologic Response
Time frame: up to 4 years
Kaplan-Meier Estimates for Duration of Best Cytogenetic Response
Time frame: up to 4 years
Kaplan-Meier Estimates for Time to Disease Progression
Time frame: up to 4 years
Kaplan-Meier Estimates for Overall Survival
Time frame: up to 4 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Nov 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 22896000Cortes J, Lipton JH, Rea D, Digumarti R, Chuah C, Nanda N, Benichou AC, Craig AR, Michallet M, Nicolini FE, Kantarjian H; Omacetaxine 202 Study Group. Phase 2 study of subcutaneous omacetaxine mepesuccinate after TKI failure in patients with chronic-phase CML with T315I mutation. Blood. 2012 Sep 27;120(13):2573-80. doi: 10.1182/blood-2012-03-415307. Epub 2012 Aug 15.
- MDACC Clinical TrialsLink provided by the sponsor.
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RecruitingObservational study
Collecting Blood Samples From Patients With and Without Cancer to Evaluate Tests for Early Cancer Detection
Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jorge Cortes, MD principal investigator
Univ. of Texas M.D. Anderson Cancer Center
Andreas Hochhaus, MD Prof Dr principal investigator
Mannheim der Universitat Heidelberg
32 sites in 10 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Omacetaxine mepesuccinate in people with Chronic Myeloid Leukemia, run by Teva Branded Pharmaceutical Products R&D, Inc. at 32 sites in 10 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 32 sites in United States, France, Canada, Germany, India and 5 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 Jun 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants Achieving an Overall Hematologic Response by Subpopulation and Total Population (time frame: Day 1 up to 6 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00375219, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Nov 2021.