UnknownPhase 1/2

PR104 in Treating Patients With Refractory/Relapsed Acute Leukemia

United States50 participantsStarted 2010-01

Plain-language summary

The current understanding of PR104 justifies the evaluation of PR104 in subjects with relapsed/refractory AML and ALL. These include: * Hypoxia. Leukemic bone marrow is likely to demonstrate a level of hypoxia sufficient to activate PR104 to its active metabolites PR104H and PR104M. * Myelotoxicity as the primary toxicity at MTD. In prior clinical studies in subjects with solid tumors PR104 has demonstrated myelotoxicity as the primary toxicity. This observation suggests that PR104 will exert a similar effect on leukemic cells. * AKR1C3. AML has been reported to exhibit high levels of AKR1C3 which should lead to selective activation of PR104 within both hypoxic and oxic leukemic cells. * Preclinical data. PR104 has demonstrated impressive activity in an initial study using primary human ALL in a mouse model. The initial dose finding phase of the study will provide estimates of the activity and toxicity of PR104 in subjects with refractory/relapsed AML, and determine the optimal individualized dose to give each subject based on his/her covariates (prior CR duration, prior number of salvage therapies, age). Once a potentially beneficial dose has been determined, an expanded cohort of subjects with AML or ALL will receive PR104 at a uniform dose. This information will prove valuable in defining the future clinical development of PR104, and in determining if PR104 has sufficient activity and acceptable safety in AML to warrant future phase II or phase III studies in this indication. Primary objectives * Determine the toxicities and recommended dose of PR104 when administered IV to subjects with relapsed/refractory AML and ALL. Secondary objectives * Evaluate the pharmacokinetics (PK) of PR104 and a series of PR104 metabolites * Evaluate any anti-tumor effects of PR104 * Evaluate the expression of AKR1C3 in bone marrow and leukemic cells * Evaluate potential biomarkers of hypoxia

Who can participate

Age range18 Years

SexALL

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AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

Inclusion Criteria: * Signed informed consent * Age 18 years or more * Histologically diagnosed acute myeloid leukemia (AML) or acute lymphocytic leukemia (ALL) by WHO classification * 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 up to 2 prior induction regimens, (i.e., first or second relapse); Refractory (defined as ≥5% leukemic blasts in the bone marrow) to not more than 1 prior induction regimen (defined as failure to achieve a CR or CRp following induction therapy), (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) * ECOG performance status of 0-2 * At least 2 weeks from administration of prior anti-leukemia therapy unless subject has progressed while receiving targeted therapy on a continuous dosing schedule * No remaining clinically significant toxicities from prior chemotherapy of grade 2 or greater * 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…

What they're measuring

Determine the optimal individualized dose to give each refractory/relapsed AML subject based on his/her covariates (prior CR duration, prior number of salvage therapies, age).

Timeframe: 42 days

Trial details

NCT IDNCT01037556

SponsorProacta, Incorporated

Sponsor typeINDUSTRY

Study typeINTERVENTIONAL

Primary completion2012-12