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Phase 1 Study of Terameprocol (EM-1421) in Patients With Leukemia

Primary Purpose

Leukemias, Acute Myeloid Leukemia (AML), Acute Lymphocytic Leukemia (ALL)

Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Terameprocol (EM-1421)
Sponsored by
Erimos Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Leukemias focused on measuring Adult, Leukemia, Terameprocol, Survivin, AML, ALL, ATL, CML, CLL, CMML, MDS

Eligibility Criteria

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

Inclusion Criteria:

  1. Patients with histological confirmed relapsed or refractory leukemias for which no standard therapies are available that are expected to result in durable remissions. Eligible are patients with:

    • acute myeloid leukemia (AML) by WHO or FAB classification
    • acute lymphocytic leukemia (ALL)
    • adult T cell leukemia (ATL)
    • chronic myeloid leukemia in blast crisis (CML-BP) having failed Bcr-Abl specific kinase inhibitors (e.g. imatinib and/or dasatinib)
    • chronic lymphocytic leukemia (CLL)
    • poor-risk myelodysplastic syndrome (MDS) [by WHO >10% blasts or IPSS groups: Int-2, high]
    • chronic myelomonocytic leukemia (CMML)
  2. ECOG performance status of 0-1
  3. Negative pregnancy test within 7 days of start of study drug NOTE: Men and women of child-producing potential must use effective contraceptive methods during the study (e.g. abstinence, intrauterine device [IUD], oral contraceptive or double barrier device)
  4. Written informed consent
  5. In the absence of rapidly progressing disease, the interval from prior therapies to time of study drug administration should be a minimum of 3 weeks for cytotoxic agents or at least 5 half-lives for noncytotoxic agents. Persistent chronic toxicities from prior chemotherapy must not be greater than grade 1
  6. Age greater than or equal to 18 years

  7. Patients must have the following clinical laboratory values:

    • Serum creatinine less than or equal to 2.0 mg/dl or creatinine clearance greater than 50ml/hr
    • Total bilirubin less than or equal to 1.5x the upper limit of normal unless considered due to Gilbert's syndrome
    • Alanine aminotransferase (ALT), or aspartate aminotransferase (AST) less than or equal to 3x the upper limit of normal unless considered due to organ leukemic involvement

Exclusion Criteria:

Patients with any one of the following criteria will not be eligible for study participation:

  1. Uncontrolled intercurrent illness including, but not limited to,

    • uncontrolled infection,
    • myocardial infarction within previous 3 months,
    • symptomatic congestive heart failure (New York Heart Association Class III, IV),
    • symptomatic coronary artery disease
    • cardiac arrhythmia not controlled by medication NOTE: Patients with controlled infection on antibiotic or antifungal therapy are eligible
  2. Psychiatric illness/social situations that would limit compliance with study requirements or unwillingness or inability to comply with procedures required in this protocol
  3. Patients receiving any other standard or investigational treatment for their leukemia NOTE: Hydroxyurea is allowed prior to study drug start and for the first 7 days of therapy
  4. Pregnant and nursing patients are excluded. NOTE: Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; or abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
  5. Major surgery, other than diagnostic surgery, within 4 weeks prior to Day 1
  6. Patients with known CNS disease
  7. History of allergic reactions attributed to compounds of similar chemical or biological composition to Terameprocol (EM-1421) or excipients

Sites / Locations

  • UNC, Lineberger Comprehensive Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Terameprocol (EM-1421)

Arm Description

Terameprocol (EM-1421) as a single agent given intravenously over 6 hours three times a week for two weeks followed by one week rest (two weeks on, one week off).

Outcomes

Primary Outcome Measures

Safety, maximum tolerated dose (MTD) and dose limiting toxicity (DLT) of Terameprocol (EM-1421) given as intravenous infusion three times a week in patients with leukemia

Secondary Outcome Measures

Pharmacokinetics (PK) of Terameprocol (EM-1421) given as intravenous infusion three times a week in patients with leukemia
To access anti-tumor activity

Full Information

First Posted
April 21, 2008
Last Updated
February 20, 2016
Sponsor
Erimos Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT00664677
Brief Title
Phase 1 Study of Terameprocol (EM-1421) in Patients With Leukemia
Official Title
Phase 1 Study of Terameprocol (EM-1421) a Survivin and Cyclin-Dependent Kinase-1 (Cdc2) Inhibitor, in Patients With Leukemia
Study Type
Interventional

2. Study Status

Record Verification Date
February 2016
Overall Recruitment Status
Terminated
Why Stopped
Funding constraints
Study Start Date
August 2007 (undefined)
Primary Completion Date
March 2009 (Actual)
Study Completion Date
June 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Erimos Pharmaceuticals

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
This study is designed to determine the safety, maximum tolerated dose,dose limiting toxicity of Terameprocol(EM-1421)and determine the pharmacokinetics (clearance from the blood)of Terameprocol(EM-1421)given as intravenous infusion three times a week in patients with leukemia.
Detailed Description
The dose of Terameprocol (EM-1421) will be escalated in successive cohorts of 3 patients. Patients will be entered sequentially on each dose level. If none of the first 3 patients at a dose level experience first cycle drug related dose-limiting toxicity (DLT), new patients may be entered at the next higher dose level. If 1 of 3 patients experience first cycle DLT, up to 3 more patients are started at that same dose level. If 2 or more experience first cycle DLT, no further patients are started at that dose. The MTD is the highest dose level in which <2 patients of 6 develop a first cycle DLT. New dose levels may begin accrual only if all patients at the current dose level have been observed for a minimum of 3 weeks after the last infusion of Terameprocol (EM-1421). The recommended phase 2 dose (RP2D) will be the MTD unless significant clinical activity is seen below the MTD. During the observation period of 3 weeks, additional accrual to a previously assessed lower dose level, with no documented DLTs, will be allowed with sponsor approval. Patients will be treated three times a week, with at least one day in between infusions, for two weeks followed by one week of rest. The dose for new cohorts will be escalated from 1000, to 1500 and 2200 mg or de-escalated to 500 mg if 1000 mg exceeds the MTD. The principal investigator will consult with the sponsor to determine the appropriate dose level for a new patient. At the MTD, up to 10 additional patients may be accrued in that dose cohort to further define the toxicities and response of the agent. If the initial dose level exceeds the MTD, a fallback dose level of 500 mg will be implemented. Patients are allowed to be treated with subsequent cycles of Terameprocol (EM-1421) until disease progression or until severe toxicities occur and side effects do not outweigh the benefit of study drug administration in the assessment of the treating physician. Intrapatient dose escalation Intrapatient dose escalation by one dose level may be permitted, but only if at least 3 patients in the next higher dose level have been treated and have been followed for 21 days without experiencing DLT. Decisions for intrapatient dose escalation will be made jointly by the Study Sponsor, treating physician and Principal Investigator. Terameprocol (EM-1421) as a single agent given intravenously over 6 hours three times a week for two weeks followed by one week rest (two weeks on, one week off)in the following dose cohorts starting with 1000 mg dose cohort. Dose Level -1: 500 mg Dose Level 1: 1000 mg Dose Level 2: 1500 mg Dose Level 3: 2200 mg

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Leukemias, Acute Myeloid Leukemia (AML), Acute Lymphocytic Leukemia (ALL), Adult T Cell Leukemia (ATL), Chronic Myeloid Leukemia (CML-BP), Chronic Lymphocytic Leukemia (CLL), Myelodysplastic Syndrome (MDS), Chronic Myelomonocytic Leukemia (CMML)
Keywords
Adult, Leukemia, Terameprocol, Survivin, AML, ALL, ATL, CML, CLL, CMML, MDS

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
16 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Terameprocol (EM-1421)
Arm Type
Experimental
Arm Description
Terameprocol (EM-1421) as a single agent given intravenously over 6 hours three times a week for two weeks followed by one week rest (two weeks on, one week off).
Intervention Type
Drug
Intervention Name(s)
Terameprocol (EM-1421)
Other Intervention Name(s)
Terameprocol, EM-1421, meso-Tetra-o-Methyl Nordihydroguaiaretic Acid
Intervention Description
Terameprocol (EM-1421) as a single agent given intravenously over 6 hours three times a week for two weeks followed by one week rest (two weeks on, one week off.
Primary Outcome Measure Information:
Title
Safety, maximum tolerated dose (MTD) and dose limiting toxicity (DLT) of Terameprocol (EM-1421) given as intravenous infusion three times a week in patients with leukemia
Time Frame
Adverse events and toxicity will be assessed prior to each cycle of treatment and at times when clinically indicated.
Secondary Outcome Measure Information:
Title
Pharmacokinetics (PK) of Terameprocol (EM-1421) given as intravenous infusion three times a week in patients with leukemia
Time Frame
Pharmacokinetics samples will be collected only on the first cycle of treatment with study drug from immediately prior to first study drug infusion to the end of day 12 of infusion.
Title
To access anti-tumor activity
Time Frame
Pharmacodynamic (molecular markers) samples will be collected immediately prior to, day 5 pre-dose and post-dose day 12 of each cycle of study drug administration, at remission and at relapse/or end of study (whichever occurs first).

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients with histological confirmed relapsed or refractory leukemias for which no standard therapies are available that are expected to result in durable remissions. Eligible are patients with: acute myeloid leukemia (AML) by WHO or FAB classification acute lymphocytic leukemia (ALL) adult T cell leukemia (ATL) chronic myeloid leukemia in blast crisis (CML-BP) having failed Bcr-Abl specific kinase inhibitors (e.g. imatinib and/or dasatinib) chronic lymphocytic leukemia (CLL) poor-risk myelodysplastic syndrome (MDS) [by WHO >10% blasts or IPSS groups: Int-2, high] chronic myelomonocytic leukemia (CMML) ECOG performance status of 0-1 Negative pregnancy test within 7 days of start of study drug NOTE: Men and women of child-producing potential must use effective contraceptive methods during the study (e.g. abstinence, intrauterine device [IUD], oral contraceptive or double barrier device) Written informed consent In the absence of rapidly progressing disease, the interval from prior therapies to time of study drug administration should be a minimum of 3 weeks for cytotoxic agents or at least 5 half-lives for noncytotoxic agents. Persistent chronic toxicities from prior chemotherapy must not be greater than grade 1 Age greater than or equal to 18 years Patients must have the following clinical laboratory values: Serum creatinine less than or equal to 2.0 mg/dl or creatinine clearance greater than 50ml/hr Total bilirubin less than or equal to 1.5x the upper limit of normal unless considered due to Gilbert's syndrome Alanine aminotransferase (ALT), or aspartate aminotransferase (AST) less than or equal to 3x the upper limit of normal unless considered due to organ leukemic involvement Exclusion Criteria: Patients with any one of the following criteria will not be eligible for study participation: Uncontrolled intercurrent illness including, but not limited to, uncontrolled infection, myocardial infarction within previous 3 months, symptomatic congestive heart failure (New York Heart Association Class III, IV), symptomatic coronary artery disease cardiac arrhythmia not controlled by medication NOTE: Patients with controlled infection on antibiotic or antifungal therapy are eligible Psychiatric illness/social situations that would limit compliance with study requirements or unwillingness or inability to comply with procedures required in this protocol Patients receiving any other standard or investigational treatment for their leukemia NOTE: Hydroxyurea is allowed prior to study drug start and for the first 7 days of therapy Pregnant and nursing patients are excluded. NOTE: Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; or abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. Major surgery, other than diagnostic surgery, within 4 weeks prior to Day 1 Patients with known CNS disease History of allergic reactions attributed to compounds of similar chemical or biological composition to Terameprocol (EM-1421) or excipients
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Neil Frazer, MB, ChB
Organizational Affiliation
Erimos Pharmaceutical
Official's Role
Study Director
Facility Information:
Facility Name
UNC, Lineberger Comprehensive Cancer Center
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Links:
URL
http://www.ncbi.nlm.nih.gov/pubmed/25523151
Description
Link to pubmed abstract of publication Tibes et al., Investigational New Drugs April 2015, Volume 33, Issue 2, pp 389-396

Learn more about this trial

Phase 1 Study of Terameprocol (EM-1421) in Patients With Leukemia

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