Phase II Study of TPA Plus Dexamethasone & CMT in Hematologic Malignancies
Condition: Leukemia
MeSH terms: Leukemia
Intervention: 12-O-tetradecanoylphorbol-13-acetate; Dexamethasone; Choline magnesium trisalicylate
Intervention description: The initial dose of TPA will be 1 mg/week x 3 weeks (Day 1, 8, 15). Up to 6 cycles.; Dexamethasone 10 mg PO qid will start 24h prior to TPA and continue for 24h after TPA x 3 weeks. Up to 6 cycles.; 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.
Intervention MeSH terms: Dexamethasone; Dexamethasone acetate; Choline magnesium trisalicylate; Choline; Dexamethasone 21-phosphate; BB 1101
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 1.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Acute Myelogenous Leukemia; Relapsed AML; Refractory AML

Summary:

      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.
    

Eligibility criteria:

        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.