Omacetaxine for Consolidation and Maintenance

• Sponsor: Emory University (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01873495
• Collaborator: Teva Pharmaceuticals USA (Industry)
• Enrollment: 7
• Location: 1
• Arm: 1
• Duration (Months): 62
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this pilot study is to assess the safety and tolerability of omacetaxine for consolidation in patients age 55 and older with acute myelogenous leukemia (AML) in first complete remission following induction with cytarabine and an anthracycline, and also to assess the safety and tolerability of omacetaxine for maintenance in patients age 55 and older with acute AML in first complete remission following 3 consolidation courses with omacetaxine.

Condition or Disease	Intervention/Treatment	Phase
Acute Myelogenous Leukemia (AML)	Drug: Omacetaxine	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 7 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Omacetaxine for Consolidation and Maintenance in Patients Age ≥ 55 With AML in First Remission: A Pilot Study
• Study Start Date: May 1, 2013
• Actual Primary Completion Date: Jul 1, 2018
• Actual Study Completion Date: Jul 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Omacetaxine: Consolidation/Maintenance	Drug: Omacetaxine; Omacetaxine 1.25 mg/m² sub-cutaneously twice daily for 5 consecutive days every 28 (± 8) days for 3 cycles. Patients in continuous remission after 3 cycles of consolidation will receive maintenance omacetaxine 1.25 mg/m² twice daily for 3 days, every 28 days for up to 6 cycles; Other Names: Synribo

Outcome Measures

Primary Outcome Measures

1. Disease Status Assessment Prior to Each Consolidation Cycle [14 days]

   Disease status will be assessed by a bone marrow aspirate and biopsy prior to each of 3 consolidation cycles (to ensure that patients are still in remission).

2. Assessment of Disease Status [1 month]

   Bone marrow biopsy and aspirate will be obtained.

3. Bone Marrow Aspirate to Confirm Continuous Remission [3 months]

   Bone marrow aspirate to confirm continuous remission will be obtained before starting maintenance and at 3 and 6 months from the start of maintenance.

4. Maintenance Toxicities [24 weeks]

   Toxicities will be monitored by history, physical examination, and laboratory monitoring during maintenance.

Secondary Outcome Measures

1. Consolidation Toxicities [12 weeks]

   Toxicities will be monitored by history, physical examination, and laboratory monitoring (CBC, serum chemistries to include renal and liver function tests) obtained weekly during consolidation and monthly during maintenance according to standard of care (Appendices C and D). Toxicity will be assessed according to the NCI Common Toxicity Criteria Version 4.0 (available at the NCI web site http://ctep.cancer.gov/reporting/ctc.html).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 55 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Diagnosis of AML including de novo, secondary, or with an antecedent hematologic disorder (AHD) according to the World Health Organization (WHO) criteria.

2. Age ≥ 55 years.

3. Patient eligible for standard induction chemotherapy based on Eastern Cooperative Oncology Group (ECOG) performance status and vital organ function at the discretion of the treating physician.

4. Patients who received 1-2 cycles of hypomethylating therapy (decitabine azacitidine) are eligible.

5. Provide signed written informed consent.

6. Be able to comply with study procedures and follow-up examinations.

7. Be non-fertile or agree to use birth control during the study through the end of last treatment visit.

8. Adequate renal and hepatic function at the time of second registration:

• Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN); and

• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN; and

• Serum creatinine ≤ 1.2 x ULN.

1. ECOG performance ≤ 2 at the time of second registration.

2. Patients with a history of carcinoma in remission, on no therapy or on hormonal therapy for the adjuvant treatment of breast carcinoma or prostate carcinoma are included in the study.

Exclusion Criteria:

1. Diagnosis of acute promyelocytic leukemia (APL, French-American-British [FAB] classification M3 or WHO classification of APL with t (15;17)(q22;q12), (PML/retinoic acid receptor alpha [RARa] and variants).

2. Prior treatment with omacetaxine.

3. Relapsed or refractory AML.

4. Investigational agent received within 30 days prior to the first dose of study drug. If received any investigational agent prior to this time point, drug-related toxicities must have recovered to Grade 2 or less prior to first dose of study drug.

5. Psychiatric disorders that would interfere with consent, study participation, or follow-up.

6. Systemic fungal, bacterial, viral, or other infection not controlled (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment).

7. Any other severe concurrent disease, or have a history of serious organ dysfunction or disease involving the heart, kidney, liver, or other organ system that may place the patient at undue risk to undergo the proposed therapy. This includes uncontrolled hypertension and uncontrolled diabetes, as cases of life threatening hyperglycemia have been reported (using continuous infusion at higher doses of omacetaxine).

8. Active carcinoma requiring systemic chemotherapy or radiation therapy.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Emory University Winship Cancer Institute	Atlanta	Georgia	United States	30322

Sponsors and Collaborators

• Emory University
• Teva Pharmaceuticals USA

Investigators

• Principal Investigator: Martha L. Arellano, MD, Emory University

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jan 14, 2017
• Informed Consent Form - Mar 30, 2017

More Information

Publications

None provided.

• Responsible Party: Martha Arellano, MD, Emory University
• ClinicalTrials.gov Identifier: NCT01873495
• Other Study ID Numbers: IRB00057844; Winship2176-11
• First Posted: Jun 10, 2013
• Last Update Posted: Sep 24, 2019
• Last Verified: Sep 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Leukemia, Myeloid; Leukemia, Myeloid, Acute; Homoharringtonine

Study Results

Participant Flow

Recruitment Details	Patients were enrolled between 5/8/2013 and 7/23/2018 at Winship Cancer Institute of Emory University.

Arm/Group Title	Omacetaxine: Consolidation/Maintenance
Arm/Group Description	Omacetaxine: Omacetaxine 1.25 mg/m² sub-cutaneously twice daily for 5 consecutive days every 28 (± 8) days for 3 cycles. Patients in continuous remission after 3 cycles of consolidation will receive maintenance omacetaxine 1.25 mg/m² twice daily for 3 days, every 28 days for up to 6 cycles
Period Title: Overall Study
STARTED	7
COMPLETED	0
NOT COMPLETED	7

Baseline Characteristics

Arm/Group Title	Omacetaxine: Consolidation/Maintenance
Arm/Group Description	Omacetaxine: Omacetaxine 1.25 mg/m² sub-cutaneously twice daily for 5 consecutive days every 28 (± 8) days for 3 cycles. Patients in continuous remission after 3 cycles of consolidation will receive maintenance omacetaxine 1.25 mg/m² twice daily for 3 days, every 28 days for up to 6 cycles
Overall Participants	7
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	5 71.4%
>=65 years	2 28.6%
Sex: Female, Male (Count of Participants)
Female	3 42.9%
Male	4 57.1%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	7 100%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	1 14.3%
White	6 85.7%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (Count of Participants)
United States	7 100%

Outcome Measures

1. Primary Outcome

Title	Disease Status Assessment Prior to Each Consolidation Cycle
Description	Disease status will be assessed by a bone marrow aspirate and biopsy prior to each of 3 consolidation cycles (to ensure that patients are still in remission).
Time Frame	14 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Omacetaxine: Consolidation/Maintenance
Arm/Group Description	Omacetaxine: Omacetaxine 1.25 mg/m² sub-cutaneously twice daily for 5 consecutive days every 28 (± 8) days for 3 cycles. Patients in continuous remission after 3 cycles of consolidation will receive maintenance omacetaxine 1.25 mg/m² twice daily for 3 days, every 28 days for up to 6 cycles
Measure Participants	7
Relapsed AML	0 0%
Remission	7 100%

2. Primary Outcome

Title	Assessment of Disease Status
Description	Bone marrow biopsy and aspirate will be obtained.
Time Frame	1 month

Outcome Measure Data

Analysis Population Description

Seven patients completed at least one cycle of omacetaxine.

Arm/Group Title	Omacetaxine: Consolidation/Maintenance
Arm/Group Description	Omacetaxine: Omacetaxine 1.25 mg/m² sub-cutaneously twice daily for 5 consecutive days every 28 (± 8) days for 3 cycles. Patients in continuous remission after 3 cycles of consolidation will receive maintenance omacetaxine 1.25 mg/m² twice daily for 3 days, every 28 days for up to 6 cycles
Measure Participants	7
Relapsed AML	1 14.3%
Remission	6 85.7%

3. Primary Outcome

Title	Bone Marrow Aspirate to Confirm Continuous Remission
Description	Bone marrow aspirate to confirm continuous remission will be obtained before starting maintenance and at 3 and 6 months from the start of maintenance.
Time Frame	3 months

Outcome Measure Data

Analysis Population Description

No patients entered the maintenance phase of this study.

Arm/Group Title	Omacetaxine: Consolidation/Maintenance
Arm/Group Description	Omacetaxine: Omacetaxine 1.25 mg/m² sub-cutaneously twice daily for 5 consecutive days every 28 (± 8) days for 3 cycles. Patients in continuous remission after 3 cycles of consolidation will receive maintenance omacetaxine 1.25 mg/m² twice daily for 3 days, every 28 days for up to 6 cycles
Measure Participants	0

4. Primary Outcome

Title	Maintenance Toxicities
Description	Toxicities will be monitored by history, physical examination, and laboratory monitoring during maintenance.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

No patients entered the maintenance phase of this study.

Arm/Group Title	Omacetaxine: Consolidation/Maintenance
Arm/Group Description	Omacetaxine: Omacetaxine 1.25 mg/m² sub-cutaneously twice daily for 5 consecutive days every 28 (± 8) days for 3 cycles. Patients in continuous remission after 3 cycles of consolidation will receive maintenance omacetaxine 1.25 mg/m² twice daily for 3 days, every 28 days for up to 6 cycles
Measure Participants	0

5. Secondary Outcome

Title	Consolidation Toxicities
Description	Toxicities will be monitored by history, physical examination, and laboratory monitoring (CBC, serum chemistries to include renal and liver function tests) obtained weekly during consolidation and monthly during maintenance according to standard of care (Appendices C and D). Toxicity will be assessed according to the NCI Common Toxicity Criteria Version 4.0 (available at the NCI web site http://ctep.cancer.gov/reporting/ctc.html).
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

Two participants experienced toxicities: thrombocytopenia and atrial flutter.

Arm/Group Title	Omacetaxine: Consolidation/Maintenance
Arm/Group Description	Omacetaxine: Omacetaxine 1.25 mg/m² sub-cutaneously twice daily for 5 consecutive days every 28 (± 8) days for 3 cycles. Patients in continuous remission after 3 cycles of consolidation will receive maintenance omacetaxine 1.25 mg/m² twice daily for 3 days, every 28 days for up to 6 cycles
Measure Participants	7
Thrombocytopenia	1 14.3%
Atrial Flutter	1 14.3%
No Toxicities	5 71.4%

Adverse Events

Time Frame	Adverse events were collected weekly during consolidation and monthly during maintenance.
Arm/Group Title	Omacetaxine: Consolidation/Maintenance
Arm/Group Description	Omacetaxine: Omacetaxine 1.25 mg/m² sub-cutaneously twice daily for 5 consecutive days every 28 (± 8) days for 3 cycles. Patients in continuous remission after 3 cycles of consolidation will receive maintenance omacetaxine 1.25 mg/m² twice daily for 3 days, every 28 days for up to 6 cycles
All Cause Mortality
	Omacetaxine: Consolidation/Maintenance
	Affected / at Risk (%)	# Events
Total	0/7 (0%)
Serious Adverse Events
	Omacetaxine: Consolidation/Maintenance
	Affected / at Risk (%)	# Events
Total	1/7 (14.3%)
Cardiac disorders
Atrial flutter	1/7 (14.3%)
Other (Not Including Serious) Adverse Events
	Omacetaxine: Consolidation/Maintenance
	Affected / at Risk (%)	# Events
Total	1/7 (14.3%)
Blood and lymphatic system disorders
Thrombocytopenia	1/7 (14.3%)

Limitations/Caveats

Accrual was halted early due to the inability of 30% of subjects to complete the intended consolidation and maintenance.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.