Phase II Study of TPA Plus Dexamethasone & CMT in Hematologic Malignancies

Study Overview
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Brief Summary
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This phase II trial is studying the side effects and how well giving tetradecanoylphorbol acetate together with dexamethasone and choline magnesium trisalicylate works in treating patients with relapsed or refractory acute myeloid leukemia.

Official Title
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A Phase II Study of 12-O-tetradecanoylphorbol-13-acetate (TPA) Plus Dexamethasone & Choline Magnesium Trisalicylate in the Treatment of Patients With Relapsed/Refractory Acute Myelogenous Leukemia

Conditions
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Leukemia

Intervention / Treatment
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* Drug: 12-O-tetradecanoylphorbol-13-acetate
* Drug: Dexamethasone
* Drug: Choline magnesium trisalicylate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Must have a histologically documented relapsed/refractory AML for which there is no standard therapy that has been demonstrated to have curative or palliative potential. ECOG performance status of 0-2. Must be 18 years or older. Estimated life expectancy > 1 month. Laboratory data: total bilirubin ≤ 1.5 x upper limit of normal unless due to Gilbert's syndrome serum creatinine ≤ 2.0 mg/dl AST ≤ 3.0 x upper limit of normal Cardiac ejection fraction > 40% FEV1.0 > 50% predicted Prior therapy: > 3 weeks since chemotherapy, biological therapy or radiation; anticipated maximum hematological improvement since last dose of chemotherapy. (Concurrent hydroxyurea administration will be allowed to control WBC count, platelet count, or symptoms). No active infections. Negative pregnancy test for women of childbearing potential. No uncontrolled psychiatric illness or medical illness that the principal investigator feels will compromise the patient's tolerance of the study medication. Must provide informed consent. Exclusion Criteria Patients with an allergy to proton pump inhibitors, required for GI prophylaxis; or salicylates are excluded. Pregnant or lactating women Age <18 years. Because no dosing or adverse event data are currently available on the use of TPA alone or in combination with dexamethasone in patients < 18 years of age, children are excluded from this study but will be eligible for future pediatric Phase II combination trials. The effects of TPA on the developing human fetus are unknown. For this reason, women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation and for 10 weeks after. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. Should the female partner of a participant in this study become pregnant or suspect she is pregnant during this study, the PI of this study will be available to provide advice about further medical/obstetric care/referral for the female partner. Patients with active CNS involvement (documented by radiographic lesions and/or malignant cells in the CSF) will be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. Patients with treatment of any other investigational drug within the last 30 days prior to entering the study.

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: TPA + Dexamethasone and CMT<br>12-O-tetradecanoylphorbol-13-acetate (TPA) plus Dexamethasone & Choline magnesium trisalicylate (Trilisate) | Drug: 12-O-tetradecanoylphorbol-13-acetate<br>* The initial dose of TPA will be 1 mg/week x 3 weeks (Day 1, 8, 15). Up to 6 cycles.<br>* Other names: TPA;Drug: Dexamethasone<br>* Dexamethasone 10 mg PO qid will start 24h prior to TPA and continue for 24h after TPA x 3 weeks. Up to 6 cycles.<br>* Other names: Dexamethasone sodium phosphate;Drug: Choline magnesium trisalicylate<br>* Choline magnesium trisalicylate 1500 mg PO TID will begin 24h prior to TPA and continue for 24h post TPA x 3 weeks. Up to 6 cycles.<br>* Other names: Trilisate;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response Rate > 20% for 12-O-tetradecanoylphorbol-13- Acetate (TPA)+ Dexamethasone + Choline Magnesium Trisalicylate(Trilisate) |  | 42 months | 
| Grade 3 and 4 Non-hematologic Treatment-related Toxicity Rates < 25% |  | 43 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effects of Treatment on Immunophenotype, Signaling Profile, and Nuclear NF-kB Expression | Cycle 1 of treatment | 48 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute Myelogenous Leukemia, Relapsed AML, Refractory AML