Leukemia
Conditions
Keywords
Acute Myelogenous Leukemia, Relapsed AML, Refractory AML
Brief 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.
Interventions
DRUG12-O-tetradecanoylphorbol-13-acetate
The initial dose of TPA will be 1 mg/week x 3 weeks (Day 1, 8, 15). Up to 6 cycles.
DRUGDexamethasone
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.
Sponsors
Rutgers Cancer Institute of New Jersey
National Cancer Institute (NCI)
Biosuccess Biotech Co., Ltd.
Rutgers, The State University of New Jersey
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | 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
| Measure | Time frame | Description |
|---|---|---|
| Effects of Treatment on Immunophenotype, Signaling Profile, and Nuclear NF-kB Expression | 48 months | Cycle 1 of treatment |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| TPA + Dexamethasone and CMT 12-O-tetradecanoylphorbol-13-acetate (TPA) plus Dexamethasone & Choline magnesium trisalicylate (Trilisate)
12-O-tetradecanoylphorbol-13-acetate: The initial dose of TPA will be 1 mg/week x 3 weeks (Day 1, 8, 15).
Up to 6 cycles.
Dexamethasone: 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: 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. | 1 |
| Total | 1 |
Baseline characteristics
| Characteristic | TPA + Dexamethasone and CMT |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 1 Participants |
| Region of Enrollment United States | 1 participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 1 |
| serious Total, serious adverse events | 1 / 1 |
Outcome results
Primary
Grade 3 and 4 Non-hematologic Treatment-related Toxicity Rates < 25%
Time frame: 43 months
Population: The study participant died before the study data collection completed.
Primary
Response Rate > 20% for 12-O-tetradecanoylphorbol-13- Acetate (TPA)+ Dexamethasone + Choline Magnesium Trisalicylate(Trilisate)
Time frame: 42 months
Population: The study participant died before the study data collection completed.
Secondary
Effects of Treatment on Immunophenotype, Signaling Profile, and Nuclear NF-kB Expression
Cycle 1 of treatment
Time frame: 48 months
Population: The study participant died before the study data collection completed.