Diamond Blackfan AnemiaPhase 1/2DBANCT03966053

The Use of Trifluoperazine in Transfusion Dependent DBA

A Phase 1/2 study testing Trifluoperazine in people with Diamond Blackfan Anemia and Pure Red Cell Aplasia, run by Adrianna Vlachos, MD at 2 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

Who is it for?: Ages 18 to 65 years
Conditions the study is for: Diamond Blackfan Anemia, Pure Red Cell Aplasia
What is being tested?: Trifluoperazine
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 2 participants
Where: 2 sitesUnited States
Study dates: 13 Sep 2019to 13 Oct 2021
Phase: Phase 1/2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 65 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

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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.

Who cannot join

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.

Show all 11Show fewer

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

Trial locations and contacts

2 sites in 1 country.

United States2 sites

Boston Children's hospital
Boston, Massachusetts, 02115
The Feinstein Institute for Medical Research
Manhasset, New York, 11030

Other trials in United States

About this study

Official title: Phase I/II, Open Label Study to Determine Safety of Trifluoperazine (TFP) in Adults With Red Blood Cell Transfusion-Dependent Diamond Blackfan Anemia

Diamond Blackfan anemia (DBA) is a rare inherited pure red cell aplasia. The two main non-stem cell transplant therapeutic options are corticosteroids and red blood cell (RBC) transfusions. About 80% of DBA patients initially respond to corticosteroids, however, half of the patients cannot continue due to side effects or loss of response. These patients are then typically dependent on RBC transfusions throughout life. Each of these treatments is fraught with many side effects and significant morbidity and mortality are potential consequences of hematopoietic stem cell transplantation (SCT). The majority of individuals with DBA have mutations in genes encoding structural proteins of the small or large ribosomal subunit leading to deficiency of the particular ribosomal protein (RP). Using the RP deficient zebrafish embryo model, high throughput drug screens have demonstrated a strong hematologic response to several calmodulin inhibitors. One of these chemicals is trifluoperazine (TFP). TFP treatment of a mouse model of DBA also increased the red blood cell count and the hemoglobin (Hb) levels in the mice. TFP is a FDA-approved typical antipsychotic agent that has been available since 1958 with a well-known safety profile. In the United States, TFP is approved for the short-term treatment of generalized non-psychotic anxiety; treatment or prevention of nausea and vomiting of various causes; and, management of psychotic disorders.

This study aims to determine the safety/tolerability of TFP in adult subjects with DBA. TFP's expected dose-limiting toxicity is primarily neurologic (extrapyramidal) when used long-term at typical anti-psychotic doses (range 10-50 mg daily). Non-neurologic adverse effects in subjects with DBA have not been investigated. We will perform a dose escalation study to define the safety and tolerability of lower doses of this agent in subjects with DBA. To mitigate the potential risks of administering TFP to this new population, we will (1) start dosing at dose levels well below those prescribed for psychosis, (2) dose escalate to a maximum of 10 mg daily (the lowest dose typically prescribed for psychosis), and (3) perform weekly safety monitoring. Given the positive signal in DBA animal models and the 60-year clinical experience with higher doses of TFP, this drug warrants a trial in humans to assess tolerability in DBA.

Read the detailed description

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.

Conditions: Diamond Blackfan Anemia, Pure Red Cell Aplasia
Being tested: Trifluoperazine
Keywords: Diamond Blackfan Anemia
Medical subject headings: Anemia, Diamond-Blackfan, Red-Cell Aplasia, Pure

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

TrifluoperazineDrug
Also called TFP
Trifluoperazine (TFP)1mg, 2mg, 5mg, or 10mg will be given once daily by mouth for 21 days

Study groups in NCT03966053
Study group	Role	What they receive
Cohort A	Experimental	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. Receives: Drug: Trifluoperazine
Cohort B	Experimental	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. Receives: Drug: Trifluoperazine
Cohort C	Experimental	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. Receives: Drug: Trifluoperazine
Cohort D	Experimental	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. Receives: Drug: Trifluoperazine

What is being measured

The primary outcome is the main question the study is designed to answer.

Number of Participants With Treatment-related Adverse Events as Assessed by the Simpson-Angus Scale and CTCAE v4.0
Each subject will undergo weekly safety assessment using the Simpson-Angus Extrapyramidal Side Effects Scale to determine the safety of TFP in this new population of patients. The subjects will also undergo weekly bloodwork to evaluate for any liver or kidney abnormalities as well as a complete blood count and reticulocyte count. All dosed subjects will be followed for an additional 1 week after discontinuing study drug (post-study safety follow-up). There will be no more than 6 subjects enrolled at any particular time.
Treatment will be discontinued for any subject if their Hb is > 12 gm/dL , and not associated with RBC transfusions.
Measured: 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.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

13 Sep 201913 Oct 2021

First posted29 May 2019
Study start13 Sep 2019
Primary completion13 Oct 2021
Study completion13 Oct 2021

Why it stopped: Supporter terminated study due to slow subject accrual secondary to COVID pandemic limiting travel to research site.

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Diamond Blackfan AnemiaStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1/2
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Sequential
Model description: Dose escalation study
Masking: None (open label)
Enrolment: 2 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03966053
Sponsor's protocol ID: 17-0748
Acronym: DBA
Status last verified: Nov 2022
First submitted: 23 May 2019
Last updated: 14 Dec 2022
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Cancer in Inherited Bone Marrow Failure Syndromes
Diamond Blackfan Anemia, Dyskeratosis Congenita
RecruitingObservational study
Mobilization of CD34+ Peripheral Blood Stem Cells in Patients With Diamond Blackfan Anemia Syndrome (DBAS)
Diamond Blackfan Anemia
RecruitingPhase 2
AlloSCT for Malignant and Non-malignant Hematologic Diseases Utilizing Alpha/Beta T Cell and CD19+ B Cell Depletion
Acute Leukemia, Severe Aplastic Anemia
RecruitingPhase 1/2
T-Cell Depleted Alternative Donor Bone Marrow Transplant for Sickle Cell Disease (SCD) and Other Anemias
Sickle Cell Anemia, Beta-thalassemia Major
RecruitingPhase 1
Assessing the Safety, Tolerability, and Efficacy of APR-2020 in Pediatric and Adolescent Subjects With RPS19 Deficient Diamond-Blackfan Anemia
RPS19 Deficient Diamond-Blackfan Anemia

All Diamond Blackfan Anemia trials

Study at a glance

From the registry record, last updated by the sponsor on 14 Dec 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Phase I/II, Open Label Study to Determine Safety of Trifluoperazine (TFP) in Adults With Red Blood Cell Transfusion-Dependent Diamond Blackfan Anemia
ClinicalTrials.gov ID: NCT03966053
Acronym / sponsor ID: DBA / 17-0748
Conditions: Diamond Blackfan Anemia, Pure Red Cell Aplasia
Keywords: Diamond Blackfan Anemia
Phase: Phase 1/2
Study type: Interventional
Recruitment status: TerminatedReason stopped: Supporter terminated study due to slow subject accrual secondary to COVID pandemic limiting travel to research site.
Enrolment: 2 participants (actual)
Lead sponsor: Adrianna Vlachos, MDUniversity, hospital or other
Study start: 13 Sep 2019 (actual)
Primary completion: 13 Oct 2021 (actual)
Study completion: 13 Oct 2021 (actual)
First posted: 29 May 2019 (actual)
Results: Posted 14 Dec 2022

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

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.

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Sequential
Masking: None (open label)
Number of arms: 4
Model description: Dose escalation study

Arm	Type	Receives
Cohort A	Experimental	Drug: TrifluoperazineCohort 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	Experimental	Drug: TrifluoperazineCohort 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	Experimental	Drug: TrifluoperazineCohort 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	Experimental	Drug: TrifluoperazineCohort 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.

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (9 listed)

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

Key exclusion criteria (11 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
TrifluoperazineAlso: TFPTrifluoperazine (TFP)1mg, 2mg, 5mg, or 10mg will be given once daily by mouth for 21 days	Drug	Cohort A, Cohort B, Cohort C, Cohort D

Primary outcome

Number of Participants With Treatment-related Adverse Events as Assessed by the Simpson-Angus Scale and CTCAE v4.0
Time frame: 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.
Each subject will undergo weekly safety assessment using the Simpson-Angus Extrapyramidal Side Effects Scale to determine the safety of TFP in this new population of patients. The subjects will also undergo weekly bloodwork to evaluate for any liver or kidney abnormalities as well as a complete blood count and reticulocyte count. All dosed subjects will be followed for an additional 1 week after discontinuing study drug (post-study safety follow-up). There will be no more than 6 subjects enrolled at any particular time. Treatment will be discontinued for any subject if their Hb is > 12 gm/dL , and not associated with RBC transfusions.

Results and safety

Results posted to the registry on 14 Dec 2022, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Cohort A	2	1

Primary outcome: Number of Participants With Treatment-related Adverse Events as Assessed by the Simpson-Angus Scale and CTCAE v4.0

Time frame: 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.. Count of participants. Unit: Participants

Measure	Cohort A n = 1
Value	0

Population analysed: One subject received study drug. The other subject did not receive study drug.

Adverse events

Time frame: 4 weeks. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Cohort A	0 of 1 (0%)	0 of 1 (0%)	0 of 1

Limitations and caveats (from the sponsor): Protocol closed early due to slow accrual secondary to COVID travel restrictions.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 14 Dec 2022.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: No

Related trials for Diamond Blackfan Anemia

RecruitingObservational study
Cancer in Inherited Bone Marrow Failure Syndromes
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RecruitingObservational study
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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Adrianna Vlachos, MD principal investigator

Northwell Health

2 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Trifluoperazine in people with Diamond Blackfan Anemia and Pure Red Cell Aplasia, run by Adrianna Vlachos, MD at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 14 Dec 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 14 Dec 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Treatment-related Adverse Events as Assessed by the Simpson-Angus Scale and CTCAE v4.0 (time frame: 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.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03966053.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Dec 2022.