Clinical trial NCT04629651: Captopril Use on the Degree of Marrow Fibrosis in Bone Marrow Fibrosis/Myeloproliferative Neoplasms
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
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
PHASE2
Conditions: Bone Marrow Fibrosis
Myeloproliferative Neoplasm
Keywords: primary myelofibrosis (PMF)
post-polycythemia vera/essential thrombocythemia-MF (secondary MF)
Lead sponsor: Case Comprehensive Cancer Center
Sponsor class: OTHER
First posted: 2020-11-16
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Detailed 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.

Eligibility criteria: 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study-related procedure is done that is not part of standard medical care, with the understanding that consent may be withdrawn by the participants any time without prejudice to future medical care.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

Primary outcomes:
measure: Change in degree of bone marrow fibrosis by World Health Organization WHO grade
timeFrame: At 6 months
Secondary outcomes:
measure: Change in spleen size by ultrasound
timeFrame: At 3 months
measure: Change in spleen size by ultrasound
timeFrame: At 6 months
measure: Change in symptom burden assessed using Myeloproliferative Neoplasm Symptom Assessment Form total symptom scores (MPN-SAF TSS)
timeFrame: At 3 months
measure: Change in symptom burden assessed using MPN-SAF TSS
timeFrame: At 6 months
measure: 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
timeFrame: Up to 1 year from end of treatment
Other outcomes:
Locations:
city: Cleveland
country: United States
facility: Cleveland Clinic, Case Comprehensive Cancer Center
state: Ohio
Study officials:
affiliation: Cleveland Clinic, Case Comprehensive Cancer Center
name: Aaron Gerds, MD
role: PRINCIPAL_INVESTIGATOR
References: