The Use of Trifluoperazine in Transfusion Dependent DBA (DBA)
Diamond Blackfan Anemia, Pure Red Cell Aplasia
About this trial
This is an interventional treatment trial for Diamond Blackfan Anemia focused on measuring Diamond Blackfan Anemia
Eligibility Criteria
Inclusion Criteria:
- Men and women age: 18 years and <65 years of age.
- Weight: ≥45 kilograms.
- DBA diagnosed according to the DBA criteria (Vlachos, 2008)
- RBC transfusion-dependence (defined as 2 units packed RBCs per 28 days averaged over 84 days [12 weeks] prior to study entry)
- Calculated creatinine clearance > 30 mL/min
- Karnofsky performance status scale score ≥ 70
- Female subjects of childbearing potential must have a negative serum pregnancy test and use highly effective methods of birth control during the study
- Male subjects must agree to use a latex condom during any sexual contact with females of childbearing potential while participating in the study
- Agreement to adhere to the study visit schedule, understand and comply with all protocol requirements.
Exclusion Criteria:
- Liver: aspartate aminotransferase (AST) > 5 x the upper limit of normal (ULN), alanine aminotransferase (ALT) >5 x ULN, or bilirubin > 5 x ULN
- Heart disease (New York Heart Association classification of ≥ 3)
- History of angina
- Uncontrolled hypertension
- Subjects currently responsive to corticosteroids for treatment of DBA.
- Treatment with another investigational drug or device <56 days pre-study entry.
- Pregnant or lactating females
- Any history of severe allergic reaction requiring the use of epinephrine
- Known hypersensitivity to the study drug or other phenothiazines
- History or presence of extrapyramidal signs
- History of cancer
Sites / Locations
- Boston Children's hospital
- The Feinstein Institute for Medical Research
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Experimental
Experimental
Experimental
Experimental
Cohort A
Cohort B
Cohort C
Cohort D
Cohort A: Three subjects will receive Trifluoperazine (TFP) 1 mg PO daily. If there is no non-neurologic toxicity Grade 3 at the end of the 21 days, Cohort B will start. If 1/3 subjects in Cohort A demonstrates toxicity Grade 3, an additional 3 subjects will be enrolled in Cohort A. If 2 or more of the 6 subjects in Cohort A demonstrate toxicity Grade 3, the trial will be stopped; no MTD will be declared. If less than 2 of the 6 subjects in Cohort A demonstrate toxicity Grade 3 within 21 days of starting therapy, Cohort B will start.
Cohort B: Three subjects will receive TFP 2 mg PO daily. If there is no non-neurologic toxicity Grade 3 at the end of the 21 days, Cohort C will start. If 1/3 subjects in Cohort B demonstrates toxicity Grade 3, an additional 3 subjects will be enrolled in Cohort B: If 2 or more of the 6 subjects in Cohort B demonstrate toxicity Grade 3, the study will be stopped, and 1 mg/day will be declared the MTD. If < 2 of the 6 subjects in Cohort B demonstrate toxicity Grade 3 within 21 days of starting therapy, Cohort C will start.
Cohort C: Three subjects will receive TFP 5 mg PO daily. If there is no non-neurologic toxicity ≥ Grade 3 at the end of the 21 days, Cohort D will start. If 1/3 subjects in Cohort C demonstrates toxicity Grade 3, an additional 3 subjects will be enrolled in Cohort C: If 2 or more of the 6 subjects in Cohort C demonstrate toxicity Grade 3, the study will be stopped, and 2 mg/day will be declared the MTD. If < 2 of the 6 subjects in Cohort C demonstrate toxicity Grade 3 within 21 days of starting therapy, cohort D will start.
Cohort D: Three subjects will receive TFP 10 mg PO daily. If 0/3 subjects in Cohort D demonstrates toxicity Grade 3, the study will be stopped, and 10 mg/day will be declared the MTD. If 1/3 subjects in Cohort D demonstrates toxicity Grade 3, an additional 3 subjects will be enrolled in Cohort D. If 2 or more of the 6 subjects in Cohort D demonstrate toxicity Grade 3, the study will be stopped, and 5 mg/day will be declared the MTD. If <2 of the 6 subjects in Cohort D demonstrate toxicity > Grade 3 within 21 days of starting therapy, 10mg/day will be declared the MTD.