The Use of Trifluoperazine in Transfusion Dependent DBA
Kulcsszavak
Absztrakt
Leírás
This is a dose escalation safety/tolerability study to evaluate the presence of TFP-related adverse events in DBA subjects, and to determine the maximum tolerated dose (MTD) of TFP in DBA.
If tolerated, this trial will support either a proof of concept trial of low-dose TFP in DBA, or the advancement of a chemically modified TFP-like drug (to alleviate the neurologic toxicity) for the treatment of DBA.
Dátumok
| Utolsó ellenőrzés: | 02/29/2020 |
| Első benyújtás: | 05/22/2019 |
| Becsült beiratkozás benyújtva: | 05/23/2019 |
| Első közzététel: | 05/28/2019 |
| Utolsó frissítés beküldve: | 03/01/2020 |
| Utolsó frissítés közzétéve: | 03/02/2020 |
| A tanulmány tényleges kezdési dátuma: | 09/12/2019 |
| Becsült elsődleges befejezési dátum: | 05/31/2021 |
| A tanulmány becsült befejezési dátuma: | 05/31/2022 |
Állapot vagy betegség
Beavatkozás / kezelés
Drug: Trifluoperazine
Fázis
Karcsoportok
| Kar | Beavatkozás / kezelés |
|---|---|
| Experimental: Cohort A 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. | |
| Experimental: Cohort B 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. | |
| Experimental: Cohort C 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. | |
| Experimental: Cohort D 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. |
Jogosultsági kritériumok
| Tanulásra alkalmas korok | 18 Years Nak nek 18 Years |
| Tanulásra alkalmas nemek | All |
| Egészséges önkénteseket fogad | Igen |
| Kritériumok | 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 |
Eredmény
Elsődleges eredménymérők
1. Number of participants with treatment-related adverse events as assessed by the Simpson-Angus Scale and CTCAE v4.0 [The subjects will be evaluated weekly for 4 weeks after the start of the 21-day course, 3 weeks while on the study drug and one week after completion.]
