Phase I/II Study of PR104 in Subjects with Refractory/Relapsed Acute Leukemia using Adaptive Dose Selection
The goal of this clinical research study is to find the highest tolerable dose of PR104 that can be given to patients with AML. After the highest tolerable dose is found, additional patients with AML or ALL will be enrolled in this study. Another goal of this clinical research study is to learn if PR104 can help to control AML and ALL. The safety of the study drug will also be studied.
Disease Group: Hematologic Disorder,Leukemia
Treatment Agent: PR104
Treatment Location: Both at MD Anderson & outside MD Anderson at one or more Collaborating Sites or Institutions
Estimatated Length of Stay in Houston: PR104 will be administered primarily on an outpatient basis. PR104 may be ;administered as an inpatient based at the discretion of the treating ;physician.The length of hospital stay is 1-2 days every 2-3 weeks during 3 ;cycles of induction.
Sponsor: Proacta Inc.
Return Visit: 1-3 times weekly during induction courses (1-3), then weekly during consolidation courses (1-4) if administered at MDACC. If during the consolidation courses the patients are followed by the local oncologist, they must come to MDACC every 3 weeks.
Home Care: Supportive care only.
Primary objectives: Determine the toxicities and recommended dose of PR104 when administered IV to subjects with refractory/relapsed acute leukemia. Secondary objectives: 1. Evaluate the pharmacokinetics (PK) of PR104 and a series of PR104 metabolites.. 2. Evaluate the efficacy of PR104. 3. Evaluate the expression of Aldo-Keto Reductase (AKR1C3) in bone marrow and leukemic cells. 4. Evaluate potential biomarkers of hypoxia.
IRB Review and Approval Date: 02/11/2010
Recruitment Status: Not Accepting
Projected Accrual: 50
1) Signed informed consent.
2) Age 18 years or more.
3) Histologically diagnosed acute myeloid leukemia (AML) or acute lymphocytic leukemia (ALL) by WHO classification.
4) Refractory or relapsed disease (requiring at least 5% leukemic blasts in the bone marrow, regardless of the presence of other features such as new or recurrent dysplastic changes or extramedullary disease) according to the following definitions: AML - Relapsed (defined as >/=5% leukemic blasts in the bone marrow) after receiving 1prior induction regimen, (i.e., first relapse); - Refractory (defined as >/=5% leukemic blasts in the bone marrow) to not more than 1 prior induction regimen (i.e., up to 1 induction failure). ALL - Relapsed/refractory (defined as >/=5% leukemic blasts in the bone marrow) after receiving 1 or more prior induction regimens (i.e., any number of relapses)
5) ECOG performance status of 0-2.
6) At least 2 weeks from administration of prior anti-leukemia therapy unless subject has progressed while receiving targeted therapy on a continuous daily dosing schedule.
7) No remaining clinically significant toxicities from prior chemotherapy of grade 2 or greater.
8) Women of child-bearing potential (i.e., women who are pre-menopausal or not surgically sterile) must be willing to use an acceptable contraceptive method (abstinence, oral contraceptive or double barrier device) for the duration of the study and for 30 days following the last dose of study drug, and must have a negative urine or serum pregnancy test within 2 weeks prior to beginning treatment on this trial.
9) Sexually active men must be willing to use an acceptable contraceptive method for the duration of time on study and for 30 days following the last dose of study drug.
10) Clinical laboratory values within the following ranges unless considered due to leukemic organ involvement: - Serum creatinine </=2.0 mg/dl. - Total bilirubin </=1.5X the upper limits of normal unless considered due to Gilbert's syndrome; - Alanine iminotransferase (ALT), or aspartate aminotransferase (AST) </=3X the upper limit of normal.
11) Willingness to provide at least one pre-PR104 leukemia sample (e.g., bone marrow or peripheral blood) that contains greater than or equal to 5% leukemic blasts for analysis of AKR1C3 (if peripheral blood samples demonstrates less than 5% leukemic blasts, must be willing to undergo a bone marrow.)
1) Pregnant and nursing subjects.
2) Uncontrolled intercurrent illness including, but not limited to uncontrolled infection, symptomatic congestive heart failure, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
3) Active heart disease including myocardial infarction within previous 3 months, symptomatic coronary artery disease, arrhythmias not controlled by medication, or uncontrolled congestive heart failure.
4) Another active concomitant malignancy likely to effect any of the primary or secondary outcome measures in the current study.
5) Subjects receiving any other standard or investigational treatment for their hematologic malignancy (other than hydroxyurea). Subjects with CNS leukemia are eligible and may receive concurrent standard intrathecal chemotherapy.
Information and next steps
Phase I/Phase II
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