Bone Marrow Fibrosis, Myeloproliferative Neoplasm
Conditions
Keywords
primary myelofibrosis (PMF), post-polycythemia vera/essential thrombocythemia-MF (secondary MF)
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.
Interventions
DRUGCaptopril
Oral, to be administered per the dose escalation scheme.
Sponsors
Case Comprehensive Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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study-related procedure is done that is not part of standard medical care, with the understanding that consent may be withdrawn by the participants any time without prejudice to future medical care.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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in degree of bone marrow fibrosis by World Health Organization WHO grade | At 6 months | 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) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in spleen size by ultrasound | At 3 months | Change in spleen size in centimeters measured using abdominal ultrasound by an experienced radiologist. Spleen length will be asses for response |
| 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 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. |
| Change in symptom burden assessed using MPN-SAF TSS | At 6 months | 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. |
| 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 | 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 \<upper normal limit (UNL); Neutrophil count ≥1 x 10\^9/L and \<UNL; Platelet count ≥100 x 10\^9/L and \<UNL;\<2% immature myeloid cells Clinical: Resolution of disease symptoms; Spleen & liver not palpable; No evidence of extramedullary hematopoiesis (EMH) PR: Periph. blood: Hem. ≥10 g/dL and \<UNL; Neutrophil count ≥1 x 10\^9/L and \<UNL; Platelet count ≥100 x 10\^9/L & \<UNL;\<2% immature myeloid cells OR Bone marrow: \[See CR\] AND Peripheral blood: Hem. ≥85, but \<10 g/dL & \<UNL; Neutrophil count ≥1 x 10\^9/L & \<UNL; Platelet count ≥50, but \<100 x 109/L and \<UNL; \<2% immature myeloid cells Clinical:\[See CR\] CI: Achievement of anemia, spleen, or symptoms response without progressive disease or increase in severity of anemia, thrombocytopenia, or neutropenia |
Countries
United States
Outcome results
None listed