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

Myeloproliferative Neoplasm Clinical Trial

Official title:

Phase I/II Prospective Trial Investigating the Safety and Efficacy of Captopril Use on the Degree of Marrow Fibrosis in Patients With Primary or Secondary Bone Marrow Fibrosis/Myeloproliferative Neoplasms

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT04629651
• Other study ID #: CASE3920
• Status: Withdrawn
• Phase: Phase 1/Phase 2
• Start date: April 2024
• Est. completion date: October 2024

Study information

• Verified date: October 2023
• Source: Case Comprehensive Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

Captopril is an investigational (experimental) drug that works by inhibiting the production of angiotensin II by blocking angiotensin converting enzyme. Reducing angiotensin II may reduce the bone marrow scar tissue in myelofibrosis. It is not approved by the Food and Drug Administration (FDA) for this indication. Participants in this study will be asked to have 2 bone marrow biopsies, a total of 3 blood samples, and fill out questionnaires asking about how you feel.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: October 2024
• Est. primary completion date: October 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Bone Marrow Fibrosis
• Fibrosis
• Myeloproliferative Disorders
• Myeloproliferative Neoplasm
• Neoplasms
• Primary Myelofibrosis

Intervention

Drug:
• Captopril
Oral, to be administered per the dose escalation scheme.

Locations

Country	Name	City	State
United States	Cleveland Clinic, Case Comprehensive Cancer Center	Cleveland	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
Case Comprehensive Cancer Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Change in spleen size by ultrasound	Change in spleen size in centimeters measured using abdominal ultrasound by an experienced radiologist. Spleen length will be asses for response	At 3 months
Secondary	Change in spleen size by ultrasound	Change in spleen size in centimeters measured using abdominal ultrasound by an experienced radiologist. Spleen length will be asses for response	At 6 months
Secondary	Change in symptom burden assessed using Myeloproliferative Neoplasm Symptom Assessment Form total symptom scores (MPN-SAF TSS)	Change in symptom burden assessed using MPN-SAF TSS The MPN-SAF TSS is assessed by the patients themselves and this includes fatigue, concentration, early satiety, inactivity, night sweats, itching, bone pain, abdominal discomfort, weight loss, and fevers. Scoring is from 0 (absent/as good as it can be) to 10 (worst imaginable/as bad as it can be) for each item. The MPN-SAF TSS is the summation of all the individual scores (0-100 scale). Symptoms response requires =50% reduction in the MPN-SAF TSS.	At 3 months
Secondary	Change in symptom burden assessed using MPN-SAF TSS	Change in symptom burden assessed using Myeloproliferative Neoplasm Symptom Assessment Form total symptom scores (MPN-SAF TSS).; The MPN-SAF TSS is assessed by the patients themselves and this includes fatigue, concentration, early satiety, inactivity, night sweats, itching, bone pain, abdominal discomfort, weight loss, and fevers. Scoring is from 0 (absent/as good as it can be) to 10 (worst imaginable/as bad as it can be) for each item. The MPN-SAF TSS is the summation of all the individual scores (0-100 scale). Symptoms response requires =50% reduction in the MPN-SAF TSS.	At 6 months
Secondary	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	Includes Complete response (CR), partial remission (PR) or Clinical improvement (CI); CR: Bone marrow: Age-adjusted normocellularity; <5% blasts; =grade 1 MF; AND; Peripheral blood: Hemoglobin =10 g/dL and PR: Periph. blood: Hem. =10 g/dL and OR; Bone marrow: [See CR]; AND; Peripheral blood: Hem. =85, but <10 g/dL & CI: Achievement of anemia, spleen, or symptoms response without progressive disease or increase in severity of anemia, thrombocytopenia, or neutropenia	Up to 1 year from end of treatment