Study of Hypoxia-Activated Prodrug TH-302 to Treat Advanced Leukemias

NCT01149915 | Completed Phase 1

• 1 other identifier: TH-CR-407
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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 myelogenous leukemia (CML), high risk myelodysplastic syndromes, advanced myelofibrosis or relapsed/refractory chronic lymphocytic leukemia (CLL).

Conditions

Acute Myelogenous Leukemia; Acute Lymphoblastic Leukemia; Chronic Myelogenous Leukemia; High-risk Myelodysplastic Syndrome; Chronic Lymphocytic Leukemia; Advanced Myelofibrosis

Keywords

Advanced Leukemias; Relapsed/Refractory Leukemias; AML; ALL; CML; MDS; CLL; MF; Evofosfamide

Outcome Measures

Primary Outcomes (3)

• To determine the maximum tolerated dose of TH-302

  2 years

• To determine the dose-limiting toxicity of TH-302

  2 years

• TO determine the number of participants with Adverse Events as a measure of safety and tolerability

  2 years

Secondary Outcomes (1)

• To determine the efficacy of TH-302 via specific response criteria

  2 years

Interventions

TH-302 DRUG

TH-302 will be administered as a 30-minute intravenous infusion daily for 5 days every 21 days. Patients who successfully complete a 3-week treatment cycle without evidence of significant treatment-related toxicity or clinically significant progressive disease will continue to receive treatment for up to six cycles.

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Threshold Pharmaceuticals: lead

Study Sites (1)

University of Texas M.D. Anderson Cancer Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

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

Interventions

TH 302

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; 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

Study Officials

• Marina Konopleva, MD, PhD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

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: June 1, 2010
• First Posted: June 24, 2010
• Study Start: June 1, 2010
• Primary Completion: August 1, 2013
• Study Completion: August 1, 2013
• Last Updated: May 7, 2015

Record last verified: 2015-05

Locations

US (1)