Antineoplastic Agents

All Drugs and Chemicals

Homoharringtonine

Enzyme Inhibitors

1.25 mg/m2 subcutaneous twice daily for 14 days

Omacetaxine

John Nemunaitis, M.D.

PK Study of Homoharringtonine (Omacetaxine Mepesuccinate) Administered Subcutaneously to Patients With Advanced Solid and Hematologic Tumors

This is an open-label non-randomized pharmacokinetic (PK) study of Homoharringtonine (Omacetaxine Mepesuccinate) administered as a subcutaneous (SC)injection to patients with relapsed and/or refractory hematologic malignancies and to patients with advanced solid tumors with no bone marrow involvement.

Pharmacokinetic (PK) Study of Homoharringtonine (Omacetaxine Mepesuccinate) Administered Subcutaneously to Patients With Advanced Solid and Hematologic Tumors

A Pharmacokinetic Study of Homoharringtonine (Omacetaxine Mepesuccinate) Administered Subcutaneously to Patients With Advanced Solid and Hematologic Tumors

ChemGenex Pharmaceuticals

Neoplasms

Blood and Lymph Conditions

All Conditions

Symptoms and General Pathology

Rare Diseases

Leukemia

Leukemia, Myeloid

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Neoplasms by Histologic Type

Hematologic Diseases

Myeloproliferative Disorders

Bone Marrow Diseases

Chronic Disease

Disease Attributes

Chronic Graft Versus Host Disease

Myeloid Leukemia

Chronic Myeloid Leukemia

Chronic Myeloproliferative Disorders

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.

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.

Omacetaxine mepesuccinate

Jorge Cortes, MD

Andreas Hochhaus, MD Prof Dr

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.

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.

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

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

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.

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.

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).

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

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.

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.

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.

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

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).

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 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 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.

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.

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 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.

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.

Cephalon

Teva Branded Pharmaceutical Products R&D, Inc.

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 24 months.

Study participants with chronic myeloid leukemia (CML) in the chronic phase at the time of enrollment. 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.

CML: Chronic Phase

Study participants with chronic myeloid leukemia (CML) in the accelerated phase at the time of enrollment. 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.

CML: Accelerated Phase

Study participants with chronic myeloid leukemia (CML) in the blast phase at the time of enrollment. 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.

CML: Blast Phase

Total

Age, Continuous

Sex: Female, Male

Caucasian

Black

Hispanic

Asian

Other

Race/Ethnicity, Customized

Height

Weight

Body Surface Area (BSA)

Class I

Class II

Class III

Class IV

* Class I: Cardiac disease, but no symptoms and no limitation in ordinary physical activity, e.g. shortness of breath when walking, climbing stairs etc.
* Class II: Mild symptoms (mild shortness of breath and/or angina) and slight limitation during ordinary activity.
* Class III: Marked limitation in activity due to symptoms, even during less-than-ordinary activity, e.g. walking short distances (20-100 m). Comfortable only at rest.
* Class IV: Severe limitations. Experiences symptoms even while at rest. Mostly bed-bound patients.

New York Heart Association (NYHA) Classification

Grade 0

Grade 1

Grade 2

Grade 3

* Grade 0: Fully active, able to carry on all pre-disease activities without restriction;
* Grade 1: Restricted in physically strenuous activity, ambulatory and able to carry out work of a light nature;
* Grade 2: Ambulatory and capable of all self-care but unable to work. Up and about more than 50% of waking hours;
* Grade 3: Capable of only limited self-care, confined to bed or chair \> 50% of waking hours;
* Grade 4: Completely disabled. Cannot carry on any self-care. Confined to bed or chair.

Eastern Cooperative Oncology Group Performance Status

Time from Initial Chronic Myeloid Leukemia (CML) Diagnosis

Intent to treat population includes all participants who provide written informed consent and receive at least one dose of study medication.

Director, Clinical Research

Treatment included induction therapy of 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.

Total Participants

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

Percentage of Participants Achieving a Major Cytogenetic Response by Subpopulation and Total Population

>=1 TEAE

>= 1 SAE

Worst severity: Grade 1

Worst severity: Grade 2

Worst severity: Grade 3

Worst severity: Grade 4

Worst severity: Grade 5

Relation to drug: Unrelated

Relation to drug: Possibly

Relation to drug: Probably

Relation to drug: Unknown

With hematologic toxicity

Discontinued treatment due to AE

Deaths during study or follow-up

Deaths during study (outcome of SAE)

Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Subpopulation and Total

Complete

Partial

Minor

Minimal

No Response

Unevaluable

Percentage of Participants in Each Cytogenetic Response Category Representing the Degree of Suppression of the Philadelphia Chromosome (Ph+)

Intent to treat population of participants who had evaluable samples. Participants with no data for these analyses either had degraded samples or the samples were missing.

Percentage of Participants With Major Molecular Response (MMR) Representing the Degree of Suppression of BCR-ABL Transcript Levels Using the Housekeeping Gene GUS

Percentage of Participants With Major Molecular Response (MMR) Representing the Degree of Suppression of BCR-ABL Transcript Levels Using the Housekeeping Gene ABL

Complete response

Partial response

Hematologic improvement

Return to chronic phase

No evidence of leukemia

No response

Percentage of Participants in Each Hematologic Response Category

Intent to treat population of study participants who had extramedullary disease at baseline. Analysis not performed due to insufficient sample size.

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

100% reduction

75-99% reduction

50-74% reduction

25-49% reduction

1-24% reduction

0% reduction

Not assessable

Intent to treat population of participants with post-baseline assessment of T315I mutated BCR ABL

Percentage of Participants With the Largest Percentage Reduction From Baseline of T315I Mutated BCR-ABL

Intent to treat population of participants who had a response to treatment

Number of Treatment Cycles Needed to Achieve Best Hematologic Response

Intent to treat population of participants who had a cytogenetic response

Number of Treatment Cycles Needed to Achieve Best Cytogenetic Response

Kaplan-Meier Estimates for Time to Onset of Best Hematologic Response

Kaplan-Meier Estimates for Time to Onset of Best Cytogenetic Response

Intent to treat population of participants who had a response

Kaplan-Meier Estimates for Duration of Best Hematologic Response

Kaplan-Meier Estimates for Duration of Best Cytogenetic Response

Kaplan-Meier Estimates for Time to Disease Progression

Kaplan-Meier Estimates for Overall Survival

Overall Study

Philadelphia Chromosome

Leukemia, Myeloid, Chronic-Phase

Anti-Infective Agents

Cytarabine

Interferons

Interferon-alpha

Interferon-alfa-1b

Interferon alpha-2

Antiviral Agents

Antimetabolites

Immunosuppressive Agents

Immunologic Factors

Interferon alfa and cytarabine daily by subcutaneous injection. Homoharringtonine is administered by continuous infusion on days 1-5.

Recombinant Interferon Alfa

Homoharringtonine is administered by continuous infusion on days 1-5.

Omacetaxine Mepesuccinate

Hagop M. Kantarjian, MD

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining biological therapy with chemotherapy may kill more cancer cells.

PURPOSE: Phase II trial to study the effectiveness of chemotherapy with cytarabine and homoharringtonine and biological therapy with interferon alfa in treating patients with chronic phase chronic myelogenous leukemia.

OBJECTIVES: I. Determine the effectiveness of low dose cytarabine, homoharringtonine, and interferon alfa in stimulating a complete cytogenic response in patients with Philadelphia chromosome positive early chronic phase chronic myelogenous leukemia. II. Evaluate the duration of the cytogenic response in these patients after this treatment. III. Determine differential success rates and analyze results by prognostic subsets (e.g., risk group, splenomegaly, thrombocytosis, age, etc.) in this patient population.

OUTLINE: Patients receive debulking therapy consisting of hydroxyurea until blood count is at proper level. Patients then receive interferon alfa and cytarabine daily by subcutaneous injection. Homoharringtonine is administered by continuous infusion on days 1-5. Treatment continues for 5-7 years in the absence of unacceptable toxicity or disease progression (accelerated or blastic phase CML). If complete remission is achieved, peripheral blood stem cells are collected. Patients are followed every 3 months for the first year and every 6 months thereafter.

PROJECTED ACCRUAL: A total of 100 patients will be accrued for this study within 3 years.

Chemotherapy and Biological Therapy in Treating Patients With Chronic Phase Chronic Myelogenous Leukemia

Therapy of Early Chronic Phase Chronic Myelogenous Leukemia (CML) With Alpha Interferon (IFN-A), Low-Dose Cytosine Arabinoside (ARA-C), and Homoharringtonine (HHT)

National Cancer Institute (NCI)

M.D. Anderson Cancer Center

Amino Acids

Tyrosine Kinase Inhibitors

Tyrosine

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.

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.

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.

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.

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

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

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.

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).

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 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.

Study participants with chronic myeloid leukemia (CML) in the chronic phase at the time of enrollment. 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 24 months.

Study participants with chronic myeloid leukemia (CML) in the accelerated phase at the time of enrollment. 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 24 months.

Study participants with chronic myeloid leukemia (CML) in the blast phase at the time of enrollment. 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 24 months.

Not available

Intent to Treat Population: all participants who provided written informed consent and received at least 1 dose of study drug constitute the ITT population.

Treatment included induction therapy of 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 24 months.

Study participants chronic myeloid leukemia (CML) in the chronic phase at the time of enrollment. 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 24 months.

Clinical response

Intent to treat population of study participants who had extramedullary disease at baseline

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Pharmacokinetic (PK) Study of Homoharringtonine (Omacetaxine Mepesuccinate) Administered Subcutaneously to Patients With Advanced Solid and Hematologic Tumors	NCT00675350	Hematologic Tum...	Omacetaxine	18 Years -	Teva Branded Pharmaceutical Products R&D, Inc.
Homoharringtonine (Omacetaxine Mepesuccinate) in Treating Patients With Chronic Myeloid Leukemia (CML) With the T315I BCR-ABL Gene Mutation	NCT00375219	Chronic Myeloid...	Omacetaxine mep...	18 Years -	Teva Branded Pharmaceutical Products R&D, Inc.
Chemotherapy and Biological Therapy in Treating Patients With Chronic Phase Chronic Myelogenous Leukemia	NCT00003239	Leukemia	Recombinant Int... Cytarabine Omacetaxine Mep...	12 Years -	M.D. Anderson Cancer Center
Homoharringtonine (Omacetaxine Mepesuccinate) in Treating Patients With Chronic Myeloid Leukemia (CML) With the T315I BCR-ABL Gene Mutation	NCT00375219	Chronic Myeloid...	Omacetaxine mep...	18 Years -	Teva Branded Pharmaceutical Products R&D, Inc.
Open Label Study of Subcutaneous Homoharringtonine (Omacetaxine Mepesuccinate) in Patients With Advanced CML	NCT00462943	Chronic Myeloid...	Omacetaxine mep...	18 Years -	Teva Branded Pharmaceutical Products R&D, Inc.
Pharmacokinetic (PK) Study of Homoharringtonine (Omacetaxine Mepesuccinate) Administered Subcutaneously to Patients With Advanced Solid and Hematologic Tumors	NCT00675350	Hematologic Tum...	Omacetaxine	18 Years -	Teva Branded Pharmaceutical Products R&D, Inc.
Chemotherapy and Biological Therapy in Treating Patients With Chronic Phase Chronic Myelogenous Leukemia	NCT00003239	Leukemia	Recombinant Int... Cytarabine Omacetaxine Mep...	12 Years -	M.D. Anderson Cancer Center
Open Label Study of Subcutaneous Homoharringtonine (Omacetaxine Mepesuccinate) in Patients With Advanced CML	NCT00462943	Chronic Myeloid...	Omacetaxine mep...	18 Years -	Teva Branded Pharmaceutical Products R&D, Inc.

Spots Global Cancer Trial Database for hht

Every month we try and update this database with for hht cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for hht

Every month we try and update this database with for hht cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for hht cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.