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Omacetaxine in Patients With Intermediate-1 and Higher Risk Myelodysplastic Syndrome (MDS) Post Hypomethylating Agent (HMA) Failure

Primary Purpose

Leukemia

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Omacetaxine

About this trial

This is an interventional treatment trial for Leukemia focused on measuring Leukemia, Myelodysplastic Syndrome, MDS, Omacetaxine, Synribo, Homoharringtonine

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Age >/= 18 years
Diagnosis of MDS confirmed within 10 weeks prior to study entry according to WHO criteria. Patients are either not eligible for or choose not to proceed with a stem cell transplant.
MDS classified as follows: RAEB-1 (5%-9% BM blasts); RAEB-2 (10%-19% BM Blasts); CMML (5%-19% BM blasts); RAEB-t (20%-29% BM blasts) AND/OR by IPSS: intermediate-1 and high risk patients.
No response, progression, or relapse (according to 2006 IWG criteria) following at least 4 cycles of either azacitidine or decitabine, which were completed within the last 2 years - AND/OR - intolerance to azacitidine or decitabine defined as drug-related >/= grade 3 hepatic or renal toxicity leading to treatment discontinuation during the preceding 2 years.
Eastern Cooperative Oncology Group (ECOG) performance status of </= 2.
Willing to adhere to and comply with all prohibitions and restrictions specified in the protocol.
Patient (or patient's legally authorized representative) must have signed an informed consent document indicating that the patient understands the purpose of and procedures required for the study and is willing to participate in the study.)

Exclusion Criteria:

Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia.
Active infection not adequately responding to appropriate antibiotics (i.e. ongoing temperatures of >/= 38 degree Celsius).
Total bilirubin >/= 1.5 mg/dL and not related to hemolysis or Gilbert's disease. Patients with total bilirubin >/= 1.5 mg/dL to 3 mg/dL are eligible if at least 75% of the bilirubin is indirect.
Alanine transaminase (ALT/SGPT) or aspartate transaminase (AST/SGOT) >/= 2.5 x the upper limit of normal.
Serum creatinine > 1.5 mg/dL.
Female patients who are pregnant or lactating.
Patients with reproductive potential who are unwilling to following contraception requirements (including condom use for males with sexual partners, and for females: prescription oral contraceptives [birth control pills], contraceptive injections, intrauterine devices [IUD], double-barrier method [spermicidal jelly or foam with condoms or diaphragm], contraceptive patch, or surgical sterilization) throughout the study.
Female patients with reproductive potential who do not have a negative urine or blood beta-human chorionic gonadotropin (beta HCG) pregnancy test at screening.
Patients receiving any other concurrent investigational agent or chemotherapy, radiotherapy, or immunotherapy.
Prior hydroxyurea for control of leukocytosis or use of hematopoietic growth factors (eg, G-CSF, GM-CSF, procrit, aranesp, thrombopoietins) is allowed at any time prior to or during study if considered to be in the best interest of the patient.
Psychiatric illness or social situation that would limit the patient's ability to comply with study requirements.

Sites / Locations

University of Texas MD Anderson Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Omacetaxine

Arm Description

Omacetaxine 1.25 mg/m2 subcutaneously every 12 hours on Days 1-3 of every 28-day study cycle. Participant may continue taking the study drug for up to 24 cycles of treatment.

Outcomes

Primary Outcome Measures

Overall Survival (OS)

Overall survival defined as the time from treatment start to the time of death. Overall survival continuously monitored using the Bayesian method.

Number of Participants With a Response

Response is Complete Response (CR) + Partial Response (PR) + Hematologic Improvement (HI). CR is the normalization of the peripheral blood and bone marrow with </= 5% bone marrow blasts, a peripheral blood granulocyte count >/= (1.0x10^9/L, and a platelet count >/= 100x10^9/L). PR is the same as CR except for the presence of 6-15% marrow blasts, or 50% reduction if <15% at start of treatment. HI meets all of the criteria for CR except for platelet recovery to >/=100x10^9L.

Secondary Outcome Measures

Full Information

NCT ID

NCT02159872

First Posted

June 6, 2014

Last Updated

May 14, 2021

Sponsor

M.D. Anderson Cancer Center

Collaborators

Teva Pharmaceuticals USA

1. Study Identification

Unique Protocol Identification Number

NCT02159872

Brief Title

Omacetaxine in Patients With Intermediate-1 and Higher Risk Myelodysplastic Syndrome (MDS) Post Hypomethylating Agent (HMA) Failure

Official Title

A Phase II Study of Omacetaxine (OM) in Patients With Intermediate-1 and Higher Risk Myelodysplastic Syndrome (MDS) Post Hypomethylating Agent (HMA) Failure

Study Type

Interventional

2. Study Status

Record Verification Date

May 2021

Overall Recruitment Status

Completed

Study Start Date

May 18, 2015 (Actual)

Primary Completion Date

April 14, 2020 (Actual)

Study Completion Date

April 14, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

M.D. Anderson Cancer Center

Collaborators

Teva Pharmaceuticals USA

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

The goal of this clinical research study is learn if omacetaxine can help to control myelodysplastic syndrome (MDS). The safety of this drug will also be studied. This is an investigational study. Omacetaxine is FDA approved and commercially available for the treatment of chronic myelogenous leukemia (CML). It is investigational to use omacetaxine in patients with MDS. The study doctor can explain how the study drug is designed to work. Up to 80 participants will be enrolled in this study. All will take part at MD Anderson.

Detailed Description

Study Drug Administration: Each cycle will be 4-7 weeks, depending on how well the disease responds to the study drug. If you are found to be eligible to take part in this study, you will receive omacetaxine as an injection under your skin 2 times each day, about 12 hours apart, on Days 1-3 of every 28-day study cycle. You will receive instructions on how to give these injections to yourself. You will be given a Research Drug Diary to record the drug you take each day. You must bring the Research Drug Diary and any unused drug with you to each study visit. You will also be told how to properly store the drugs. Depending on how the disease responds to the study drugs, the number of days you receive your injections may stay the same, increase, or decrease. Your doctor will discuss this with you. During Cycle 1, if the doctor thinks it is needed, you will be given hydroxyurea by mouth to decrease the risk of side effects. You may ask the study staff for information about how the drug is given and its risks. Study Visits: At the beginning of every cycle, you will have a physical exam before your dose of study drug. Every week (+/- 2 days), blood (about 2-3 teaspoons) will be drawn for routine tests. If the disease appears to get better, this blood will only be drawn every 2-4 weeks while you are still receiving the study drugs. If you live far from the clinic, this blood can be drawn at a clinic close to your home, and the results will be reported to the study doctor. If the study doctor thinks it is needed, you may have an additional bone marrow aspirate at any time during the study to check the status of the disease and for cytogenetic testing. Length of Study: You may continue taking the study drug for up to 24 cycles of treatment. You will no longer be able to take the study drug if the disease gets worse, if intolerable side effects occur, or if you are unable to follow study directions. Your participation on the study will be over after the follow-up visits. Follow-Up: You will have follow-up visits at the clinic every 3-6 months for up to 5 years after you stop taking the study drug. You will be asked about your health and any new drugs you may be taking. If you cannot come to the clinic, you will be called by the study staff and asked about your health. These calls should last about 5-10 minutes. Every 4-8 weeks after your last dose of study drug, blood (about 2-3 teaspoons) will be drawn for routine tests.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Leukemia

Keywords

Leukemia, Myelodysplastic Syndrome, MDS, Omacetaxine, Synribo, Homoharringtonine

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

48 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Omacetaxine

Arm Type

Experimental

Arm Description

Omacetaxine 1.25 mg/m2 subcutaneously every 12 hours on Days 1-3 of every 28-day study cycle. Participant may continue taking the study drug for up to 24 cycles of treatment.

Intervention Type

Drug

Intervention Name(s)

Omacetaxine

Other Intervention Name(s)

Synribo, Homoharringtonine

Intervention Description

1.25 mg/m2 subcutaneously every 12 hours on Days 1-3 of every 28-day study cycle.

Primary Outcome Measure Information:

Title

Overall Survival (OS)

Description

Overall survival defined as the time from treatment start to the time of death. Overall survival continuously monitored using the Bayesian method.

Time Frame

Up to 2.5 Years

Title

Number of Participants With a Response

Description

Time Frame

Up to 2 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Age >/= 18 years Diagnosis of MDS confirmed within 10 weeks prior to study entry according to WHO criteria. Patients are either not eligible for or choose not to proceed with a stem cell transplant. MDS classified as follows: RAEB-1 (5%-9% BM blasts); RAEB-2 (10%-19% BM Blasts); CMML (5%-19% BM blasts); RAEB-t (20%-29% BM blasts) AND/OR by IPSS: intermediate-1 and high risk patients. No response, progression, or relapse (according to 2006 IWG criteria) following at least 4 cycles of either azacitidine or decitabine, which were completed within the last 2 years - AND/OR - intolerance to azacitidine or decitabine defined as drug-related >/= grade 3 hepatic or renal toxicity leading to treatment discontinuation during the preceding 2 years. Eastern Cooperative Oncology Group (ECOG) performance status of </= 2. Willing to adhere to and comply with all prohibitions and restrictions specified in the protocol. Patient (or patient's legally authorized representative) must have signed an informed consent document indicating that the patient understands the purpose of and procedures required for the study and is willing to participate in the study.) Exclusion Criteria: Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia. Active infection not adequately responding to appropriate antibiotics (i.e. ongoing temperatures of >/= 38 degree Celsius). Total bilirubin >/= 1.5 mg/dL and not related to hemolysis or Gilbert's disease. Patients with total bilirubin >/= 1.5 mg/dL to 3 mg/dL are eligible if at least 75% of the bilirubin is indirect. Alanine transaminase (ALT/SGPT) or aspartate transaminase (AST/SGOT) >/= 2.5 x the upper limit of normal. Serum creatinine > 1.5 mg/dL. Female patients who are pregnant or lactating. Patients with reproductive potential who are unwilling to following contraception requirements (including condom use for males with sexual partners, and for females: prescription oral contraceptives [birth control pills], contraceptive injections, intrauterine devices [IUD], double-barrier method [spermicidal jelly or foam with condoms or diaphragm], contraceptive patch, or surgical sterilization) throughout the study. Female patients with reproductive potential who do not have a negative urine or blood beta-human chorionic gonadotropin (beta HCG) pregnancy test at screening. Patients receiving any other concurrent investigational agent or chemotherapy, radiotherapy, or immunotherapy. Prior hydroxyurea for control of leukocytosis or use of hematopoietic growth factors (eg, G-CSF, GM-CSF, procrit, aranesp, thrombopoietins) is allowed at any time prior to or during study if considered to be in the best interest of the patient. Psychiatric illness or social situation that would limit the patient's ability to comply with study requirements.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Elias Jabbour, MD

Organizational Affiliation

M.D. Anderson Cancer Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of Texas MD Anderson Cancer Center

City

Houston

State/Province

Texas

ZIP/Postal Code

77030

Country

United States

12. IPD Sharing Statement

Links:

URL

http://www.mdanderson.org

Description

University of Texas MD Anderson Cancer Center Website

Learn more about this trial

Omacetaxine in Patients With Intermediate-1 and Higher Risk Myelodysplastic Syndrome (MDS) Post Hypomethylating Agent (HMA) Failure

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