Captopril Use on the Degree of Marrow Fibrosis in Bone Marrow Fibrosis/Myeloproliferative Neoplasms

NCT04629651 | Withdrawn Phase 1 DMC FDA Drug

• 1 other identifier: CASE3920
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the safety and tolerability of captopril and evaluate the effectiveness captopril as measured by changes in the grade of bone marrow scar tissue. The change in spleen size by ultrasound will also be measured.

Conditions

Bone Marrow Fibrosis; Myeloproliferative Neoplasm

Keywords

primary myelofibrosis (PMF); post-polycythemia vera/essential thrombocythemia-MF (secondary MF)

Outcome Measures

Primary Outcomes (1)

• Change in degree of bone marrow fibrosis by World Health Organization WHO grade

  Change in degree of bone marrow fibrosis by WHO grade. "Change" is defined as reduction by one grade (e.g. MF-3 to MF-2 or MF-2 to MF-1)

  At 6 months

Secondary Outcomes (5)

• Change in spleen size by ultrasound

  At 3 months

• Change in spleen size by ultrasound

  At 6 months

• Change in symptom burden assessed using Myeloproliferative Neoplasm Symptom Assessment Form total symptom scores (MPN-SAF TSS)

  At 3 months

• Change in symptom burden assessed using MPN-SAF TSS

  At 6 months

• Response rate per International Working Group-Myeloproliferative Neoplasms Research and Treatment 2 (IWG-MRT) Criteria as measured by percent of participants with CR, PR, or CI

  Up to 1 year from end of treatment

Study Arms (1)

Captopril

EXPERIMENTAL

In phase I, Cohorts of 3 patients each will receive doses of captopril with a goal dose of 150mg total by mouth (PO) daily. Initial dose per patient will start at 12.5 mg daily, which will then be increased on weekly intervals as tolerated. To be administered per the intra-patient dose escalation scheme below Phase I: Day 0: 12.5mg/day Day 7: 12.5mg twice daily Day 14: 12.5mg three times daily Day 21: 25mg three times daily Day 28: 50mg three times daily Phase II: The efficacy of captopril will be assessed in the Phase II portion. Captopril given at Maximum Tolerated Dose - bone marrow evaluation to be done at 6 months

Drug: Captopril

Interventions

Captopril DRUG

Oral, to be administered per the dose escalation scheme.

Captopril

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must have histologically confirmed diagnosis of primary myelofibrosis (PMF), or post-polycythemia vera/essential thrombocythemia-MF (i.e. secondary MF) by 2016 WHO criteria
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0 -2
• Creatinine clearance \>30 ml/minute
• Women of childbearing potential should be advised to avoid becoming pregnant while receiving treatment. All men and women of childbearing potential must use acceptable methods of birth control throughout the study.
• Participants should be able to give voluntary informed written consent to participate in the study. Informed consent will be obtained prior to enrollment and before any study-related procedure is done that is not part of standard medical care, with the understanding that consent may be withdrawn by the participants any time without prejudice to future medical care.

You may not qualify if:

• Completed hematopoietic cell transplant (HCT)
• Presence of \>10% blasts in peripheral blood or on bone marrow examination
• Screening blood pressure(BP)parameters of systolic BP \< 100 and diastolic BP \< 60
• Splenic irradiation within 3 months prior to the first dose of captopril
• Prior ACE inhibitor, angiotensin II receptor antagonist, or aliskiren use within 12 months prior to trial enrolment
• Known allergy/hypersensitivity to ACE inhibitors
• Participants receiving any other investigational agents
• Pregnant or nursing participants - captopril is a risk category D and is excreted in breast milk
• Participants with creatinine clearance \<30 ml/minute or on dialysis
• Any serious medical condition, laboratory abnormality, or psychiatric illness that, in the view of the treating physician, would place the participant at an unacceptable risk if he or she were to participate in the study or would prevent that person from giving informed consent

Sponsors & Collaborators

• Case Comprehensive Cancer Center: lead

Study Sites (1)

Cleveland Clinic, Case Comprehensive Cancer Center

Cleveland, Ohio, 44122, United States

Location

MeSH Terms

Conditions

Primary Myelofibrosis; Myeloproliferative Disorders

Interventions

Captopril

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Proline; Imino Acids; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Aaron Gerds, MD

  Cleveland Clinic, Case Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 10, 2020
• First Posted: November 16, 2020
• Study Start: April 1, 2024
• Primary Completion: October 1, 2024
• Study Completion: October 1, 2024
• Last Updated: October 11, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL

Locations

US (1)