Status:
COMPLETED
Study of Hypoxia-Activated Prodrug TH-302 to Treat Advanced Leukemias
Lead Sponsor:
Threshold Pharmaceuticals
Conditions:
Acute Myelogenous Leukemia
Acute Lymphoblastic Leukemia
Eligibility:
All Genders
18+ years
Phase:
PHASE1
Brief Summary
The primary objective of this study is to determine the maximum tolerated dose, dose limiting toxicity, safety and tolerability of TH-302 in patients with acute leukemias, advanced phase chronic myelo...
Detailed Description
Tumor hypoxia has been associated with resistance to chemotherapy and radiotherapy (Brown et al, 2004; Boyle 2006). TH-302, a hypoxia activated prodrug (HAP), exploits the hypoxic nature of tumors whi...
Eligibility Criteria
Inclusion
- At least 18 years of age.
- 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.
- Relapsed/refractory leukemias for which no standard therapy options are anticipated to result in a durable remission.
- Acute myelogenous leukemia (AML) by WHO classification relapsed or refractory to standard chemotherapy; unsuitable for standard chemotherapy or unwilling to undergo standard chemotherapy.
- 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 tyrosinekinase inhibitor therapy.
- Chronic myelogenous leukemia (CML) in accelerated or blast phase failing prior tyrosine kinase-containing therapy
- High-risk myelodysplastic syndrome (MDS) \[i.e. refractory anemia with excess blasts (RAEB-1 or RAEB-2) by WHO classification\] or chronic myelomonocytic leukemia (CMML) with \>5% marrow blasts, relapsed or refractory to standard therapy
- Chronic lymphocytic leukemia (CLL) relapsed or refractory to standard therapy, not eligible for protocols of higher priority
- Advanced myelofibrosis (MF) resistant or refractory to standard therapy; or untreated with one of following features (1) hemoglobin \< 10 g/dL, (2) platelet count \< 100 x 109/L, WBC \< 4 or \> 30 x 109/L, or splenomegaly ≥ 10 cm below left costal margin
- Age \> 60 years with AML not candidates for or have refused standard chemotherapy, excluding subjects with acute promyelocytic leukemia (APL) or with favorable cytogenetic abnormalities \[inv16, t(8;21)\].
- ECOG performance status of less than or equal to 3
- Adequate organ function as indicated by the following laboratory assessments performed within 14 days prior to the first dose of study drug:
- Total bilirubin ≤ 1.5 times upper limit of normal (x ULN) (≤ 3 x ULN if due to leukemic involvement or Gilbert's syndrome).
- Aspartate aminotransferase or alanine aminotransferase ≤ 2.5 x ULN (≤ 5.0 x ULN if due to leukemic involvement)
- Serum creatinine ≤ 1.5 x ULN.
- All women of childbearing potential must have a negative 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
- New York Heart Association (NYHA) Class III or IV, cardiac disease, myocardial infarction within 6 months prior to Day 1, or unstable arrhythmia
- Seizure disorders requiring anticonvulsant therapy
- Severe chronic obstructive pulmonary disease with hypoxemia or in the opinion of the investigator any physiological state leading to hypoxemia
- Major surgery, other than diagnostic surgery, within 4 weeks prior to Day 1, without complete recovery
- Active uncontrolled infection
- Systemic chemotherapy (with the exception of hydroxyurea and/or steroids) within 14 days (or 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.
- Known active infection with HIV, hepatitis B, or hepatitis C
- Patients who have exhibited allergic reactions to a similar structural compound, biological agent, or formulation (containing solutol and/or propylene glycol)
- Females who are pregnant or breast-feeding
- 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
- Unwillingness or inability to comply with the study protocol for any reason
Key Trial Info
Start Date :
June 1 2010
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
August 1 2013
Estimated Enrollment :
40 Patients enrolled
Trial Details
Trial ID
NCT01149915
Start Date
June 1 2010
End Date
August 1 2013
Last Update
May 7 2015
Active Locations (1)
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1
University of Texas M.D. Anderson Cancer Center
Houston, Texas, United States, 77030