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Study Summary
No. 2010-0268:.......Leukemia; Myeloproliferative Diseases......Marina Konopleva......Leukemia
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Study Summary Title
Study Summary
Number:
2010-0268
Study Title:A Phase I Open-label Study to Assess the Safety, Tolerability and Preliminary Efficacy of TH-302, A Hypoxia-Activated Prodrug, in Patients with Advanced Leukemias
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Physician New Patient Referral
Name:Marina KonoplevaPatients Call:800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Dept:LeukemiaReferring MD
Call:
800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Phone:713-794-1628
Contact us about clinical trials
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General Information
Disease Group:Leukemia
Myeloproliferative Diseases
Supported By:Threshold Pharmaceuticals, Inc.
Phase of Study:Phase IReturn
Visit:
Treatment
Agents:
Oral Hypoxyprobe-1
TH-302
Home Care:
Treatment Loc:Only at MDACC
Estimated
Length of Stay
in Houston:
Description/
Intervention:
The goal of this clinical research study is to find the highest tolerable dose
of TH-302 that can be given to patients with leukemia. The safety of this drug
will also be studied.
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Study Objectives / Outcomes
Primary objectives:
    1. To determine the maximum tolerated dose, dose limiting toxicity, safety and tolerability of TH-302 in patients with acute leukemias, advanced phase chronic myelogenous leukemia (Arm A), high risk myelodysplastic syndromes (Arm A), advanced myelofibrosis (Arm A) or relapsed/refractory chronic lymphocytic leukemia (Arm A).

Secondary objectives:
    1. To determine the clinical activity of TH-302
    2. To evaluate the pharmacokinetics (PK) of TH-302 and Br-IPM.
The exploratory objectives are:
    1. To determine the extent of hypoxia in the bone marrow of patients with advanced leukemias
    2. To explore the association of bone marrow hypoxia and the efficacy and safety of TH-302
    3. To compare the safety and efficacy of TH-302 administered as a 30-60 minute infusion with TH-302 administered as a continuous infusion
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    Study Status Information
    Study Activation / Registration Date:06/18/2010
    IRB Review and Approval Date:06/18/2010
    Study Type:Phase I
    Recruitment Status:Open
    Projected Accrual:N/A
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    Enrollment Eligibility
    If you do not meet the enrollment eligibility, there may be other treatment options for you. Please Contact the Referral Office for more information.

    Inclusion Criteria:1) At least 18 years of age.

    2) Ability to understand the purposes and risks of the study and has signed a written informed consent form approved by the investigator's IRB/Ethics Committee.

    3) Relapsed/refractory leukemias for which no standard therapy options are anticipated to result in a durable remission: Acute myelogenous leukemia (AML), or Acute lymphoblastic leukemia (ALL) relapsed or refractory to standard chemotherapy; unsuitable for standard chemotherapy or unwilling to undergo standard chemotherapy; Philadelphia chromosome (Ph) positive ALL eligible if failed prior tyrosine-kinase inhibitor therapy; Chronic lymphocytic leukemia (CLL) relapsed or refractory to standard therapy (Arm A only); Chronic myelogenous leukemia (CML) in accelerated or blast phase failing tyrosine kinase-containing therapy (Arm A only); High-risk myelodysplastic syndrome (MDS) or chronic myelomonocytic leukemia (CMML) with >5% marrow blasts, relapsed or refractory to standard therapy (Arm A only);

    4) Continued from #3 above: Advanced myelofibrosis (MF) resistant or refractory to standard therapy; or untreated with one of following: hemoglobin < 10 g/dL, platelet count < 100 x 109/L, WBC < 4 or > 30 x 109/L, or splenomegaly >/=10 cm below costal margin (Arm A only).

    5) Age >/= 60 years with AML not candidates for or have refused standard chemotherapy, excluding subjects with acute promyelcytic leukemia (APL) or with favorable cytogenetic abnormalities [inv16, t(8;21)].

    6) ECOG performance status of less than or equal to 3.

    7) Adequate organ function as indicated by the following laboratory assessments performed within 14 days prior to the first dose of study drug: 1) Total bilirubin </= 1.5 times upper limit of normal (x ULN) (</= 3 x ULN if due to leukemic involvement or Gilbert's syndrome); 2) Aspartate aminotransferase or alanine aminotransferase </= 2.5 x ULN (</= 5.0 x ULN if due to leukemic involvement); 3) Serum creatinine </= 1.5 x ULN.

    8) All women of childbearing potential must have a negative urine or serum pregnancy test and women and men subjects must agree to use effective means of contraception (surgical sterilization or the use or barrier contraception with either a condom or diaphragm in conjunction with spermicidal gel or an IUD) with their partner from entry into the study through 6 months after the last dose.

    Exclusion Criteria:1) New York Heart Association (NYHA) Class III or IV, cardiac disease, myocardial infarction within 6 months prior to Day 1, or unstable arrhythmia.

    2) Uncontrolled seizure disorder.

    3) Severe chronic obstructive pulmonary disease with hypoxemia or in the opinion of the investigator any physiological state leading to hypoxemia.

    4) Major surgery, other than diagnostic surgery, within 4 weeks prior to Day 1, without complete recovery.

    5) Active uncontrolled infections.

    6) Systemic chemotherapy (with the exception of hydroxyurea and/or steroids) within 14 days (within 5 half-lives for an investigational agent) prior to first dose of study drug, unless there is evidence of rapidly progressive disease. Concurrent therapy for CNS prophylaxis or continuation of therapy for controlled CNS disease is permitted.

    7) Known active infection with HIV, hepatitis B, or hepatitis C.

    8) Patients who have exhibited allergic reactions to a structural compound similar to TH-302 or its excipients.

    9) Females who are pregnant or breast-feeding.

    10) Unwillingness or inability to comply with the study protocol for any reason.

    11) Concomitant disease or condition that could interfere with the conduct of the study, or that would, in the opinion of the investigator, pose an unacceptable risk to the subject in this study

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    Links
    Registration Number: NCT01149915
    Study Information on Clinical Trials Registry (clinicaltrials.gov)

    Other Links:
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    Results


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