A Study of PTX-200 (Triciribine) Plus Cytarabine in Refractory or Relapsed Acute Leukemia

Study Overview
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Brief Summary
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A phase I-II open label study of PTX-200 in combination with cytarabine in the treatment of relapsed or refractory acute leukemia.

Detailed Description
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Study design: Phase I/II study The Phase I study is open-label with four increasing dose levels for up to four 21-day cycles. Safety and activity will be evaluated at the end of each cycle. The Phase II study is open label with administration of the recommended phase dose of PTX-200 for up to four 21-day cycles. PTX-200 will be co-administered with cytarabine in both the Phase I and Phase II parts of the study.

Official Title
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A Phase I-II Study of Triciribine Phosphate Monohydrate (PTX-200) Plus Cytarabine in Refractory or Relapsed Acute Leukemia

Conditions
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Acute Leukemia

Intervention / Treatment
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* Drug: PTX-200
* Drug: Cytarabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pathologic confirmation of the diagnosis of AML, ALL (acute lymphoblastic leukemia), or blast-phase CML (chronic myelogenous leukemia) Age ≥ 18 years ECOG Performance Status 0-2 Patients must be able to give adequate informed consent Exclusion Criteria: Hyperleukocytosis with ≥ 30,000 leukemic blasts/µL blood (hydroxyurea permitted up to 24 hours prior to beginning study drugs) Uncontrolled Disseminated Intravascular Coagulation (DIC) Uncontrolled diabetes mellitus Active, uncontrolled infection

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PTX-200 and cytarabine<br>PTX-200 administered intravenously over 1 hour Phase I: 4 dose levels: 25 to 55 mg/m2 (with reduction to 15 mg/m2 if needed. Phase II: maximum tolerated dose. given as a 1 hour infusion Cytarabine administered by continuous infusion at a dose of 400 mg/m2/day for 4 days. | Drug: PTX-200<br>* During the Phase I study, increasing dose levels of PTX-200 will be administered as an intravenous infusion on Day 1 each cycle. Triciribine will be infused over 1 hour on Day 1 of each 21 day cycle. The initial dose level will be 25 mg/m2 and each dose level will be increased by 10 mg/m2 to a maximum dose of 55 mg/m2<br>* Other names: Triciribine Phosphate Monohydrate;Drug: Cytarabine<br>* Cytarabine will be given at a dose of 400 mg/m2 as a continuous IV infusion on days 3-7 of each cycle.<br>* Other names: Ara-C;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment-related Adverse Events | Number of participants with treatment-related Adverse Events as assessed by CTCAE v4.0 that result in dose-limitations (Phase I) | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phospho-Akt (pAkt) expression within CD34+ leukemic blasts | Change from baseline phospho-Akt (pAkt) signaling within CD34+ leukemic blasts and the ability of PTX-200 to downregulate p-Akt and its signaling at a variety of times | 12 months |