EUCTR2018-000579-34-GB进行中（未招募）1 期
A Phase 1/2 Study of CPI-0610, a Small Molecule Inhibitor of BET Proteins: Phase 1 (Dose Escalation of CPI-0610 in Patients with Hematological Malignancies) and Phase 2 (Dose Expansion of CPI-0610 with and without Ruxolitinib in Patients with Myeloproliferative Neoplasms) - MANIFEST
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 297
研究概览
简要总结
暂无简介。
研究设计
- 研究类型
- Interventional clinical trial of medicinal product
入排标准
- 性别
- All
入选标准
- •Prior JAKi:
- •1. Adult (aged = 18 years)
- •2. Patients with confirmed diagnosis of MF who meet all of the following criteria:
- •a. Dynamic International Prognostic Scoring System (DIPSS) risk category of intermediate-2 or higher.
- •b. Platelet count = 75 x 10^9/L without the assistance of thrombopoietic factors or transfusions
- •c. ANC = 1 x 10^9/L without the assistance of granulocyte growth factors
- •d. Spleen volume of =450 cm3 by CT or MRI for Cohorts 1B and 2B OR RBC transfusion dependent (defined as an average of =2 units of RBC transfusions per month over the 12 weeks prior to enrollment for Cohorts 1A and 2A
- •e. Peripheral blood blast count <10%
- •f. At least 2 symptoms measurable (score = 1) using the MFSAF v4.0
- •g. Monotherapy Arm (Arm 1) patients only: Previously treated with a JAKi and be intolerant, resistant, refractory or lost response to the JAKi; have not received the JAKi within 2 weeks prior to start of study drug, or are ineligible to be treated with a JAKi
- •h. Combination Arm (Arm 2) patients only: Must have received ruxolitinib for at least 6 months and be on a stable ruxolitinib dose for a minimum 8 weeks (prior to start of study drug)
- •3. ECOG performance status = 2.
- •4. Serum direct bilirubin = 1.5 x ULN (upper limit of normal)
- •5. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) = 2.5 x ULN. The AST and /or ALT may be elevated up to 5 x ULN if the elevation can be reasonably ascribed to liver involvement.
- •6. Calculated or measured creatinine clearance (CrCl) = 45 ml/min (either measured or estimated by the Cockcroft-Gault formula).
- •7. Patients must have fully recovered from major surgery and from the acute toxic effects of prior chemotherapy and radiotherapy (residual CTCAE grade 1 toxicity, e.g., grade 1 peripheral neuropathy, and residual alopecia are allowed).
- •8. Male and female patients with reproductive potential must agree to use highly effective contraceptive methods while on study therapy and for 3 months after the last dose of CPI-0610. NOTE: Male patients should be informed of the risk of testicular toxicity and provided with adequate advice regarding sperm preservation.
- •JAKi Naive Arm 3:
- •1. Adult (aged = 18 years)
- •2. Patients with confirmed diagnosis of MF who meet all of the following criteria:
- •a. DIPSS (see Appendix 3) risk category of intermediate-1 or higher.
- •b. Platelet count = 100 x 10^9/L without the assistance of thrombopoietic factors or transfusions
- •c. ANC = 1 x 10^9/L without the assistance of granulocyte growth factors
- •d. Spleen volume = 450 cm3 by CT/MRI
- •e. Peripheral blood blast count <10%
- •f. At least 2 symptoms measurable (score = 3) or a total score of = 10 using the MFSAF v4.0
- •g. No prior treatment with JAKi allowed
- •3. ECOG performance status = 2.
- •4. Life expectancy of >24 weeks
- •5. Serum direct bilirubin < 2.0 x ULN
- •6. AST and ALT = 2.5 x ULN. The AST and /or ALT may be elevated up to 5 x ULN if the elevation can be reasonably ascribed to liver involvement.
- •7. Calculated or measured CrCL = 45 ml/min (either measured or estimated by the Cockcroft-Gault formula).
- •8. Patients with a history of transfusions must have a documented transfusion record during the 12 weeks prior to the first dose of study drug
- •9. Patients must have fully recovered from major surgery and from the acute toxic effects of prior chemotherapy and radiotherapy (residual CTCAE grade 1 toxicity, e.g., grade 1 peripheral neuropathy, and residu
排除标准
- •Prior JAKi Arm 1 and Add-on to Jaki Arm 2
- •1. Patients in Cohorts 1B and 2B: Patients who have had prior splenectomy
- •2. Patients in Cohorts 1B and 2B: Patients who have had splenic irradiation within 3 months of starting study drug
- •3. Current known active or chronic infection with HIV, Hepatitis B or Hepatitis C
- •4. Patients with active clinically significant infection will not be eligible for enrolment until recovery for at least 2 weeks prior to the first dose of study drug.
- •5. Patients wih anemia from iron deficiency, B12 and folate deficiencies hemoyltic anemia, or infection.
- •6. Serum ferritin level < lower limit of normal (LLN) as per institutional standards
- •7. Patient with a major bleeding event causing a decrease in hemoglobin of = 2g/dL or leading to transfusion of = 2 units of packed red cells in the last 6 months prior to enrollment
- •8. Patients with Child-Pugh Class B or C
- •9. GI function or GI disease that could significantly alter the absorption of CPI-0610 and/or ruxolitinib
- •10. Impaired cardiac function or clinically significant cardiac diseases, including any of the following:
- •11. Ongoing uncontrolled hypertension despite maximal antihypertensive treatment
- •12. Any other concurrent severe and/or uncontrolled concomitant medical condition that in the opinion of the investigator could compromise participation in the study or analysis of study data
- •13. Systemic anti-cancer treatment (other than ruxolitinib for the Combination Arm (Arm 2); see inclusion criterion #2) other than hydroxyurea and anagrelide less than 2 weeks (or 5 half-lives) before the first dose of CPI-0610
- •14. Any investigational agent >2 weeks (or 5 half-lives) before the first dose of CPI-0610
- •15. Prior treatment with a BET inhibitor
- •16. Hematopoietic growth factor (granulocyte growth factor, erythropoiesis stimulating agent, thrombopoietin mimetic) or androgenic steroids less than 4 weeks before the first dose of study drug
- •17. Patients in the Combination Arm (Arm 2) who are receiving treatment with fluconazole
- •18. Systemic corticosteroids at daily doses = 10 mg of oral prednisone or equivalent within 2 weeks before the first dose of study drug
- •For further exclusion criteria for Arm 1 & 2 and details please refer to the protocol)
- •JAKi Naive Arm 3:
- •1. Prior treatment with a BET inhibitor
- •2. Patients who have had a prior splenectomy
- •3. Patients who have had splenic irradiation within 3 months of starting study drug
- •4. Current known active or chronic infection with HIV, Hepatitis B or Hepatitis C
- •5. Patients with active clinically significant infection will not be eligible for enrollment until recovery for at least 2 weeks prior to the first dose of study drug
- •6. Patients with anemia from iron deficiency, B12 and folate deficiencies, hemolytic anemia or infection
- •7. Serum ferritin level < LLN as per institutional standards
- •8. Patient with a major bleeding event causing a decrease in Hgb of = 2g/dL or leading to transfusion of =2 units of packed red cells in the last 6 months prior to enrollment
- •9. Patients with Child-Pugh Class B or C
- •10. Impairment of GI function or GI disease that could significantly alter the absorption of CPI-0610 and/or ruxolitinib
- •11. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption or patients with hypersensitivity to any ingredient in the formulation of ruxolitinib
- •12. Patients who have or have had PML
- •13. Impaired cardiac function or cl
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