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.
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Oral, to be administered per the dose escalation scheme.
Cleveland Clinic, Case Comprehensive Cancer Center
Cleveland, Ohio, United States
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)
Time frame: At 6 months
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
Time frame: At 3 months
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
Time frame: At 6 months
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.
Time frame: At 3 months
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.
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Time frame: 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
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
Time frame: Up to 1 year from end of treatment