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

NCT00664677 | Terminated Phase 1

• 1 other identifier: EM-1421 #105
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• 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

  Adverse events and toxicity will be assessed prior to each cycle of treatment and at times when clinically indicated.

Secondary Outcomes (2)

• Pharmacokinetics (PK) of Terameprocol (EM-1421) given as intravenous infusion three times a week in patients with leukemia

  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.

• To access anti-tumor activity

  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).

Study Arms (1)

Terameprocol (EM-1421)

EXPERIMENTAL

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).

Drug: Terameprocol (EM-1421)

Interventions

Terameprocol (EM-1421) DRUG

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.

Also known as: Terameprocol, EM-1421, meso-Tetra-o-Methyl Nordihydroguaiaretic Acid

Terameprocol (EM-1421)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Erimos Pharmaceuticals: lead

Study Sites (1)

UNC, Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, 27599, United States

Location

Related Links

• Link to pubmed abstract of publication Tibes et al., Investigational New Drugs April 2015, Volume 33, Issue 2, pp 389-396

MeSH Terms

Conditions

Leukemia; Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Lymphocytic, Chronic, B-Cell; Myelodysplastic Syndromes; Leukemia, Myelomonocytic, Chronic

Interventions

terameprocol

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Myeloid; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Myeloproliferative Disorders; Bone Marrow Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Leukemia, B-Cell; Myelodysplastic-Myeloproliferative Diseases

Study Officials

• Neil Frazer, MB, ChB

  Erimos Pharmaceutical

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 21, 2008
• First Posted: April 23, 2008
• Study Start: August 1, 2007
• Primary Completion: March 1, 2009
• Study Completion: June 1, 2009
• Last Updated: February 23, 2016

Record last verified: 2016-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)