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

NCT00462943 | Completed Phase 2 Results DMC

• 2 other identifiers: CGX-635-CML-2032007-001286-15
• Study Type: interventional
• Target: 100
• Locations: 10 countries
• Sites: 29

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.

Conditions

Chronic Myeloid Leukemia

Keywords

CML; HHT; Homoharringtonine; Omacetaxine

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 9 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 4 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)

OMA

EXPERIMENTAL

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.

Drug: Omacetaxine mepesuccinate

Interventions

Omacetaxine mepesuccinate DRUG

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.

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

OMA

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
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (29)

Teva Investigational Site 303

Los Angeles, California, 90033, United States

Location

Teva Investigational Site 308

Beech Grove, Indiana, 46107, United States

Location

Teva Investigational Site 311

Baltimore, Maryland, 21201, United States

Location

Teva Investigational Site 305

Buffalo, New York, 14263, United States

Location

Teva Investigational Site 302

The Bronx, New York, 10466, United States

Location

Teva Investigational Site 310

Philadelphia, Pennsylvania, 19111, United States

Location

Teva Investigational Site 301

Houston, Texas, 77030, United States

Location

Teva Investigational Site 314

Seattle, Washington, 98109, United States

Location

Teva Investigational Site 313

Montreal, H3a 1a1, Canada

Location

Teva Investigational Site 309

Toronto, M5G 2M9, Canada

Location

Teva Investigational Site 329

Bordeaux, 33076, France

Location

Teva Investigational Site 321

Le Chesnay, 78157, France

Location

Teva Investigational Site 322

Lille, 59000, France

Location

Teva Investigational Site 320

Lyon, 69437, France

Location

Teva Investigational Site 324

Nice, 06202, France

Location

Teva Investigational Site 328

Paris, 75475, France

Location

Teva Investigational Site 323

Poitiers, 86021, France

Location

Teva Investigational Site 327

Strasbourg, 67100, France

Location

Teva Investigational Site 325

Toulouse, 31059, France

Location

Teva Investigational Site 331

Berlin, 10117, Germany

Location

Teva Investigational Site 330

Mannheim, 68169, Germany

Location

Teva Investigational Site 350

Budapest, 1096, Hungary

Location

Teva Investigational Site 371

Hyderabad, 500082, India

Location

Teva Investigational Site 370

Mumbai, 400 014, India

Location

Teva Investigational Site 390

Bologna, 41038, Italy

Location

Teva Investigational Site 360

Gdansk, 80-952, Poland

Location

Teva Investigational Site 361

Warsaw, 02776, Poland

Location

Teva Investigational Site 380

Singapore, 169608, Singapore

Location

Teva Investigational Site 340

London, W12 0HS, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 23468307 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

  M.D. Anderson Cancer Center

  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: April 17, 2007
• First Posted: April 19, 2007
• Study Start: March 7, 2007
• Primary Completion: August 4, 2009
• Study Completion: June 27, 2013
• Last Updated: December 28, 2021
• Results First Posted: June 30, 2014

Record last verified: 2021-12

Locations

CA (2); DE (2); US (8); IN (2); PL (2); GB (1); SG (1); FR (9); IT (1); HU (1)