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Phase I/II Study of PR104 in Subjects With Refractory/Relapsed Acute Leukemia Using Adaptive Dose Selection

Phase 1/Phase 2
18 Years
Open (Enrolling)
Acute Myelogenous Leukemia, Acute Lymphocytic Leukemia

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Trial Information

Phase I/II Study of PR104 in Subjects With Refractory/Relapsed Acute Leukemia Using Adaptive Dose Selection

A single arm study defining the recommended dose of PR104 for each subpopulation in this
patient population.

Following informed consent, subjects will undergo baseline evaluation with a history,
physical exams, blood work, and disease assessment. Subjects will be assigned a dose of
PR104 based on a Bayesian model maintained at the Statistical department at MD Anderson
Cancer Center. The model will be updated with both toxicity and efficacy data as it is
generated for each subject. New subjects will receive the currently predicted best dose for
their respective subset based on prior treatment, age and duration of prior response.

PR104 will be administered initially as induction therapy for up to 3 cycles. Response will
be assessed around day 42 (+/- 2 days) of the study. Subjects who obtain a CR or CRp will
receive consolidation therapy for up to 4 additional cycles.

Subjects will be evaluated each week during the induction phase of the study. During the
consolidation phase of the study, subjects will be evaluated on Day 1 of each cycle and as
clinically indicated. Subjects with clinically significant progression will be removed from

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

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

- 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

- 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

- 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 limit of normal unless considered due to Gilbert's syndrome; Alanine
aminotransferase (ALT), or aspartate aminotransferase (AST) 3x the upper limit of

- Willingness to provide at least one pre-PR104 leukemia sample (e.g., bone marrow or
peripheral blood) for analysis of AKR1C3.

Exclusion Criteria:

- Pregnant and nursing subjects

- 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

- Active heart disease including myocardial infarction within previous 3 months,
symptomatic coronary artery disease, arrhythmias not controlled by medication, or
uncontrolled congestive heart failure

- Another active concomitant malignancy likely to effect any of the primary or
secondary outcome measures in the current study

- 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.

Type of Study:


Study Design:

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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).

Outcome Time Frame:

42 days

Safety Issue:



United States: Food and Drug Administration

Study ID:




Start Date:

January 2010

Completion Date:

December 2012

Related Keywords:

  • Acute Myelogenous Leukemia
  • Acute Lymphocytic Leukemia
  • AML
  • Acute Myeloid Leukemia
  • Acute Myelogenous Leukemia
  • Refractory AML
  • Relapsed AML
  • Refractory Acute Myeloid Leukemia
  • Relapsed Acute Myeloid Leukemia
  • Refractory Acute Myelogenous Leukemia
  • Relapsed Acute Myelogenous Leukemia
  • ALL
  • Acute Lymphocytic Leukemia
  • Relapsed Acute Lymphocytic Leukemia
  • Refractory Acute Lymphocytic Leukemia
  • Relapsed ALL
  • Refractory ALL
  • Leukemia
  • Leukemia, Lymphoid
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid



MD Anderson Cancer CenterHouston, Texas  77030-4096
Seattle Cancer Care AllianceSeattle, Washington  98109