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NCT00462943

Open Label Study of Subcutaneous Homoharringtonine (Omacetaxine Mepesuccinate) in Patients With Advanced CML

Completed Phase 2 Results posted Last updated 28 December 2021
What this trial tests

Phase 2 trial testing Omacetaxine mepesuccinate in Chronic Myeloid Leukemia in 100 participants. Completed in 27 June 2013.

Timeline
7 March 2007
Primary endpoint
4 August 2009
27 June 2013

Quick facts

Lead sponsorTeva Branded Pharmaceutical Products R&D, Inc.
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment100
Start date7 March 2007
Primary completion4 August 2009
Estimated completion27 June 2013
Sites29 locations across France, Italy, United Kingdom, Germany, Hungary, Poland, Canada, Singapore

Drugs / interventions tested

Conditions studied

Sponsor

Teva Branded Pharmaceutical Products R&D, Inc. — full company profile →

Who can join

18 and older, any sex, with Chronic Myeloid Leukemia. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Percentage of Participants Achieving an Overall Hematologic Response by Subpopulation and Total Population Primary · 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

GroupValue95% CI
CML: Chronic Phase67.451.98 – NA
CML: Accelerated Phase25.811.86 – NA
CML: Blast Phase8.71.07 – NA
Total Participants41.031.26 – NA
Percentage of Participants Achieving a Major Cytogenetic Response by Subpopulation and Total Population Primary · Day 1 up to 9 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

GroupValue95% CI
CML: Chronic Phase21.710.95 – NA
CML: Accelerated Phase3.20.08 – NA
CML: Blast Phase00 – NA
Total Participants115.62 – NA
Percentage of Participants in Each Cytogenetic Response Category Representing the Degree of Suppression of the Philadelphia Chromosome (Ph+) Secondary · Day 1 up to Month 9

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

Complete
GroupValue95% CI
CML: Chronic Phase4.3
CML: Accelerated Phase0
CML: Blast Phase0
Total Participants2.0
Partial
GroupValue95% CI
CML: Chronic Phase17.4
CML: Accelerated Phase3.2
CML: Blast Phase0
Total Participants9.0
Minor
GroupValue95% CI
CML: Chronic Phase8.7
CML: Accelerated Phase9.7
CML: Blast Phase0
Total Participants7.0
Minimal
GroupValue95% CI
CML: Chronic Phase6.5
CML: Accelerated Phase6.5
CML: Blast Phase4.3
Total Participants6.0
No Response
GroupValue95% CI
CML: Chronic Phase39.1
CML: Accelerated Phase61.3
CML: Blast Phase30.4
Total Participants44.0
Unevaluable
GroupValue95% CI
CML: Chronic Phase23.9
CML: Accelerated Phase19.4
CML: Blast Phase65.2
Total Participants32.0
Percentage of Participants With Major Molecular Response (MMR) Representing the Degree of Suppression of BCR-ABL Transcript Levels Using the Housekeeping Gene GUS Secondary · Day 1 up to Month 6

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.

GroupValue95% CI
CML: Chronic Phase13.62.9 – 34.9
CML: Accelerated Phase0NA – NA
CML: Blast Phase0NA – NA
Total Participants6.81.4 – 18.7
Percentage of Participants With Major Molecular Response (MMR) Representing the Degree of Suppression of BCR-ABL Transcript Levels Using the Housekeeping Gene ABL Secondary · Day 1 up to Month 6

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.

GroupValue95% CI
CML: Chronic Phase10.52.9 – 24.8
CML: Accelerated Phase4.30.1 – 22.0
CML: Blast Phase0NA – NA
Total Participants6.92.3 – 15.5
Percentage of Participants in Each Hematologic Response Category Secondary · Day 1 up to Month 6

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-treatme

Complete response
GroupValue95% CI
CML: Chronic Phase67.4
CML: Accelerated Phase19.4
CML: Blast Phase8.7
Total Participants39.0
Partial response
GroupValue95% CI
CML: Chronic Phase0
CML: Accelerated Phase3.2
CML: Blast Phase0
Total Participants1.0
Hematologic improvement
GroupValue95% CI
CML: Chronic Phase0
CML: Accelerated Phase9.7
CML: Blast Phase4.3
Total Participants4.0
Return to chronic phase
GroupValue95% CI
CML: Chronic PhaseNA
CML: Accelerated Phase6.5
CML: Blast Phase0
Total Participants2.0
No evidence of leukemia
GroupValue95% CI
CML: Chronic PhaseNA
CML: Accelerated Phase0
CML: Blast Phase0
Total Participants0
No response
GroupValue95% CI
CML: Chronic Phase21.7
CML: Accelerated Phase58.1
CML: Blast Phase78.3
Total Participants46.0
Unevaluable
GroupValue95% CI
CML: Chronic Phase10.9
CML: Accelerated Phase3.2
CML: Blast Phase8.7
Total Participants8.0
Percentage of Participants With Extramedullary Disease (EMD) at Baseline Achieving a Clinical Response Secondary · Day 1 up to Month 9

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).

Clinical response
GroupValue95% CI
CML: Blast Phase0
Unevaluable
GroupValue95% CI
CML: Blast Phase50
Percentage of Participants With the Largest Percentage Reduction From Baseline of T315I Mutated BCR-ABL Secondary · Day 1 up to Month 9

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).

100% reduction
GroupValue95% CI
CML: Chronic Phase00 – 0
CML: Accelerated Phase00 – 0
CML: Blast Phase00 – 0
Total Participants00 – 0
75-99% reduction
GroupValue95% CI
CML: Chronic Phase00 – 0
CML: Accelerated Phase00 – 0
CML: Blast Phase00 – 0
Total Participants00 – 0
50-74% reduction
GroupValue95% CI
CML: Chronic Phase00 – 0
CML: Accelerated Phase00 – 0
CML: Blast Phase00 – 0
Total Participants00 – 0
25-49% reduction
GroupValue95% CI
CML: Chronic Phase00 – 0
CML: Accelerated Phase00 – 0
CML: Blast Phase9.10.3 – 52.7
Total Participants1.40.0 – 9.1
1-24% reduction
GroupValue95% CI
CML: Chronic Phase00 – 0
CML: Accelerated Phase00 – 0
CML: Blast Phase00 – 0
Total Participants00 – 0
0% reduction
GroupValue95% CI
CML: Chronic Phase78.976.4 – 100
CML: Accelerated Phase91.383.9 – 100
CML: Blast Phase63.347.4 – 99.7
Total Participants80.679.9 – 100
Not assessable
GroupValue95% CI
CML: Chronic Phase21.1NA – NA
CML: Accelerated Phase8.7NA – NA
CML: Blast Phase27.3NA – NA
Total Participants18.1NA – NA
Number of Treatment Cycles Needed to Achieve Best Hematologic Response Secondary · Day 1 up to Month 6

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.

GroupValue95% CI
CML: Chronic Phase1.01 – 5
CML: Accelerated Phase2.01 – 4
CML: Blast Phase2.01 – 3
Total Participants1.01 – 5
Number of Treatment Cycles Needed to Achieve Best Cytogenetic Response Secondary · Day 1 up to Month 9
GroupValue95% CI
CML: Chronic Phase2.01 – 9
CML: Accelerated Phase1.51 – 4
CML: Blast Phase1.01 – 1
Total Participants2.01 – 9
Kaplan-Meier Estimates for Time to Onset of Best Hematologic Response Secondary · Day 1 up to Month 6

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.

GroupValue95% CI
CML: Chronic Phase1.380.49 – 1.84
CML: Accelerated PhaseNA4.14 – NA
CML: Blast PhaseNANA – NA
Total Participants5.033.13 – NA
Kaplan-Meier Estimates for Time to Onset of Best Cytogenetic Response Secondary · Day 1 up to Month 9

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.

GroupValue95% CI
CML: Chronic PhaseNANA – NA
CML: Accelerated PhaseNANA – NA
CML: Blast PhaseNANA – NA

Adverse events — posted to ClinicalTrials.gov

Time frame: up to 4 years. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Omacetaxine
Serious: 63/100 (63%)
Deaths:

Serious adverse events (58 terms)

ReactionSystemOmacetaxine
Febrile neutropeniaBlood and lymphatic system disorders
Disease progressionGeneral disorders
ThrombocytopeniaBlood and lymphatic system disorders
Bone marrow failureBlood and lymphatic system disorders
PneumoniaInfections and infestations
DiarrhoeaGastrointestinal disorders
PyrexiaGeneral disorders
AnaemiaBlood and lymphatic system disorders
SepsisInfections and infestations
HypercalcaemiaMetabolism and nutrition disorders
Cerebral haemorrhageNervous system disorders
Febrile bone marrow aplasiaBlood and lymphatic system disorders
PancytopeniaBlood and lymphatic system disorders
Gastrointestinal haemorrhageGastrointestinal disorders
StomatitisGastrointestinal disorders
FatigueGeneral disorders
Catheter sepsisInfections and infestations
Lung infectionInfections and infestations
Failure to thriveMetabolism and nutrition disorders
Chronic myeloid leukaemiaNeoplasms benign, malignant and unspecified (incl cysts and polyps)
LeukaemiaNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Anaemia haemolytic autoimmuneBlood and lymphatic system disorders
LeukocytosisBlood and lymphatic system disorders
NeutropeniaBlood and lymphatic system disorders
Acute coronary syndromeCardiac disorders
Other adverse events (54 terms — click to expand)

ReactionSystemOmacetaxine
ThrombocytopeniaBlood and lymphatic system disorders
AnaemiaBlood and lymphatic system disorders
DiarrhoeaGastrointestinal disorders
NeutropeniaBlood and lymphatic system disorders
NauseaGastrointestinal disorders
PyrexiaGeneral disorders
FatigueGeneral disorders
HeadacheNervous system disorders
AstheniaGeneral disorders
Febrile neutropeniaBlood and lymphatic system disorders
VomitingGastrointestinal disorders
EpistaxisRespiratory, thoracic and mediastinal disorders
Abdominal painGastrointestinal disorders
Pain in extremityMusculoskeletal and connective tissue disorders
Oedema peripheralGeneral disorders
AnorexiaMetabolism and nutrition disorders
LeukopeniaBlood and lymphatic system disorders
PneumoniaInfections and infestations
CoughRespiratory, thoracic and mediastinal disorders
ConstipationGastrointestinal disorders
Injection site erythemaGeneral disorders
StomatitisGastrointestinal disorders
ChillsGeneral disorders
Disease progressionGeneral disorders
ArthralgiaMusculoskeletal and connective tissue disorders
Upper respiratory tract infectionInfections and infestations
Bone painMusculoskeletal and connective tissue disorders
Pharyngolaryngeal painRespiratory, thoracic and mediastinal disorders
LymphopeniaBlood and lymphatic system disorders
BronchitisInfections and infestations
ContusionInjury, poisoning and procedural complications
HyperuricaemiaMetabolism and nutrition disorders
HypokalaemiaMetabolism and nutrition disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
LeukocytosisBlood and lymphatic system disorders
Abdominal pain upperGastrointestinal disorders
DyspepsiaGastrointestinal disorders
Back painMusculoskeletal and connective tissue disorders
InsomniaPsychiatric disorders
AlopeciaSkin and subcutaneous tissue disorders

Most-reported serious reactions: Febrile neutropenia, Disease progression, Thrombocytopenia, Bone marrow failure, Pneumonia, Diarrhoea, Pyrexia, Anaemia.

Data from ClinicalTrials.gov NCT00462943 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Phytochemical-Based Nanomedicine for Advanced Cancer Theranostics: Perspectives on Clinical Trials to Clinical Use.
    Dhupal M, Chowdhury D. · · 2020 · cited 48× · PMID 33244231 · DOI 10.2147/ijn.s259628
  2. Phase 2 study of subcutaneous omacetaxine mepesuccinate for chronic-phase chronic myeloid leukemia patients resistant to or intolerant of tyrosine kinase inhibitors.
    Cortes J, Digumarti R, Parikh PM, Wetzler M, et al · · 2013 · cited 48× · PMID 23468307 · DOI 10.1002/ajh.23408
  3. Potential Approaches <i>Versus</i> Approved or Developing Chronic Myeloid Leukemia Therapy.
    Andretta E, Costa C, Longobardi C, Damiano S, et al · · 2021 · cited 23× · PMID 34993151 · DOI 10.3389/fonc.2021.801779
  4. Recent updates on nano-phyto-formulations based therapeutic intervention for cancer treatment.
    Wahi A, Bishnoi M, Raina N, Singh MA, et al · · 2023 · cited 20× · PMID 38188681 · DOI 10.32604/or.2023.042228
  5. Potential treatments of COVID-19: Drug repurposing and therapeutic interventions.
    Raghav PK, Mann Z, Ahluwalia SK, Rajalingam R. · · 2023 · cited 11× · PMID 37059487 · DOI 10.1016/j.jphs.2023.02.004
  6. Rare disease patients in India are rarely involved in international orphan drug trials.
    Chakraborty M, Choudhury MC, Chakraborty I, Saberwal G. · · 2022 · cited 9× · PMID 36962798 · DOI 10.1371/journal.pgph.0000890
  7. Novel targeted therapies in chronic myeloid leukemia.
    Ashaq MS, Zhou Q, Li Z, Zhao B. · · 2024 · cited 2× · PMID 41550150 · DOI 10.1016/j.pscia.2024.100052
  8. Ribosome biogenesis rate, a parameter of sensitivity to chemotherapeutic drugs inhibiting rRNA synthesis.
    Treré D, Montanaro L, Derenzini M, Agostinelli C, et al · · 2025 · PMID 41660279 · DOI 10.3389/or.2025.1740261

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Other trials of Omacetaxine mepesuccinate

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Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing