Homoharringtonine (Omacetaxine Mepesuccinate) in Treating Patients With Chronic Myeloid Leukemia (CML) With the T315I BCR-ABL Gene Mutation

NCT00375219 | Completed Phase 2 Results DMC

• 2 other identifiers: CGX-635-CML-2022006-000176-32
• Study Type: interventional
• Target: 103
• Locations: 10 countries
• Sites: 32

Brief 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.

Conditions

Chronic Myeloid Leukemia

Keywords

Chronic Myeloid Leukemia; CML; HHT; Homoharringtonine; Omacetaxine; T315i; ChemGenex; ChemGenex Pharmaceuticals

Outcome Measures

Primary Outcomes (3)

• 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.

  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.

  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).

  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+)

  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

  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

  Day 1 up to Month 6

• Percentage of Participants in Each Hematologic Response Category

  Day 1 up to Month 6

• Percentage of Participants With Extramedullary Disease (EMD) at Baseline Achieving a Clinical Response

  Day 1 up to Month 9

Study Arms (1)

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.

Drug: Omacetaxine mepesuccinate

Interventions

Omacetaxine mepesuccinate DRUG

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.

Also known as: Homoharringtonine, OMA, Synribo, HHT, CGX-635

omacetaxine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Teva Branded Pharmaceutical Products R&D, Inc.: lead
• Cephalon: collaborator
• ChemGenex Pharmaceuticals: collaborator

Study Sites (32)

Teva Investigational Site 003

Los Angeles, California, 90033, United States

Location

Teva Investigational Site 007

Jacksonville, Florida, 32224, United States

Location

Teva Investigational Site 006

Atlanta, Georgia, 30329, United States

Location

Teva Investigational Site 008

Beech Grove, Indiana, 46107, United States

Location

Teva Investigational Site 011

Baltimore, Maryland, 21201, United States

Location

Teva Investigational Site 004

Boston, Massachusetts, 02111, United States

Location

Teva Investigational Site 005

Buffalo, New York, 14263, United States

Location

Teva Investigational Site 002

The Bronx, New York, 10467, United States

Location

Teva Investigational Site 010

Philadelphia, Pennsylvania, 19111, United States

Location

Teva Investigational Site 001

Houston, Texas, 77030, United States

Location

Teva Investigational Site 013

Montreal, H3a 1a1, Canada

Location

Teva Investigational Site 009

Toronto, M5G 2M9, Canada

Location

Teva Investigational Site 029

Bordeaux, 33076, France

Location

Teva Investigational Site 021

Le Chesnay, 78157, France

Location

Teva Investigational Site 022

Lille, 59000, France

Location

Teva Investigational Site 020

Lyon, 69437, France

Location

Teva Investigational Site 024

Nice, 06202, France

Location

Teva Investigational Site 028

Paris, 75475, France

Location

Teva Investigational Site 023

Poitiers, 86021, France

Location

Teva Investigational Site 027

Strasbourg, 67100, France

Location

Teva Investigational Site 025

Toulouse, 31059, France

Location

Teva Investigational Site 026

Vandœuvre-lès-Nancy, 54511, France

Location

Teva Investigational Site 031

Berlin, 10117, Germany

Location

Teva Investigational Site 030

Mannheim, 68169, Germany

Location

Teva Investigational Site 050

Budapest, 1096, Hungary

Location

Teva Investigational Site 071

Hyderabad, 500082, India

Location

Teva Investigational Site 070

Mumbai, 400 014, India

Location

Teva Investigational Site 090

Bologna, 41038, Italy

Location

Teva Investigational Site 060

Gdansk, 80-952, Poland

Location

Teva Investigational Site 061

Warsaw, 02776, Poland

Location

Teva Investigational Site 080

Singapore, 169608, Singapore

Location

Teva Investigational Site 040

London, W12 0HS, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 22896000 DERIVED

MeSH Terms

Conditions

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Interventions

Homoharringtonine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Harringtonines; Alkaloids; Heterocyclic Compounds; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds, 4 or More Rings

Results Point of Contact

• Title: Director, Clinical Research
• Organization: Teva Branded Pharmaceutical Products, R&D Inc.

ustevatrials@tevapharm.com

215-591-3000

Study Officials

• Jorge Cortes, MD

  Univ. of Texas M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

• Andreas Hochhaus, MD Prof Dr

  Mannheim der Universitat Heidelberg

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 8, 2006
• First Posted: September 12, 2006
• Study Start: September 20, 2006
• Primary Completion: March 23, 2010
• Study Completion: June 28, 2013
• Last Updated: November 15, 2021
• Results First Posted: June 3, 2014

Record last verified: 2021-11

Locations

CA (2); IT (1); SG (1); HU (1); FR (10); GB (1); DE (2); PL (2); US (10); IN (2)