A Phase 1/2 Study of CPI-0610 With and Without Ruxolitinib in Patients With Hematologic and Myeloproliferative Malignancies

Inclusion Criteria

• •* Age: Adults ≥18 years.
• •* Diagnosis: Histologically or cytologically confirmed diagnosis of one of the following hematologic malignancies:
• •* Acute myelogenous leukemia (AML)
• •* Acute lymphocytic leukemia (ALL)
• •* Acute undifferentiated or biphenotypic leukemia
• •* Chronic myeloid leukemia (CML) in blast crisis
• •* Myelodysplastic syndrome (MDS)
• •* Myelodysplastic/myeloproliferative neoplasms (MDS/MPN)
• •* Myelofibrosis (MF)
• •* Performance Status: ECOG ≤2.
• •* Organ Function:
• •* Serum total bilirubin ≤1.5 × ULN
• •* AST/ALT ≤2.5 × ULN (up to 5 × ULN if due to leukemic infiltration)
• •* Serum creatinine ≤2.0 × ULN or CrCl ≥30 mL/min
• •* Hematology (MF only):
• •* Platelet count ≥50 × 10⁹/L and ANC ≥1 × 10⁹/L (MF not on ruxolitinib)
• •* Platelet count ≥75 × 10⁹/L and ANC ≥1 × 10⁹/L (MF on ruxolitinib)
• •* Other:
• •* DIPSS-plus risk category of intermediate-2 or high (MF only)
• •* Serum glucose ≤160 mg/dL (or HbA1C ≤7%)
• •* Fully recovered from major surgery and acute toxic effects of prior therapy
• •* Negative pregnancy test for women of childbearing potential
• •* Agreement to use appropriate contraception
• •* Written informed consent
• •1. MF Arms (Prior JAKi, Add-on JAKi, JAKi Naïve)
• •* Age: Adults ≥18 years
• •* Diagnosis: Confirmed primary MF or MF evolved from ET or PV
• •* Risk: DIPSS intermediate-2 or higher
• •* Platelets:
• •* ≥75 × 10⁹/L (Arms 1 \& 2)
• •* ≥100 × 10⁹/L (Arm 3, JAKi naïve)
• •* ANC: ≥1 × 10⁹/L
• •* Spleen Volume: ≥450 cm³ by MRI/CT (non-TD cohorts) OR
• •* Transfusion Dependence: Average ≥2 RBC transfusions/month (total ≥6 in prior 12 weeks) for TD cohorts
• •* Peripheral Blood Blasts: \<10%
• •* Symptoms: At least 2 symptoms measurable (score ≥1 for Arms 1 \& 2; score ≥3 or total ≥10 for Arm 3) using MFSAF v4.0
• •* Treatment History:
• •* Arm 1 (Prior JAKi): Previously treated with JAKi and intolerant, resistant, refractory, or lost response, or ineligible for JAKi
• •* Arm 2 (Add-on JAKi): On ruxolitinib ≥6 months, stable dose ≥8 weeks, not adequately controlled
• •* Arm 3 (JAKi Naïve): No prior JAKi, eligible for ruxolitinib
• •* Performance Status: ECOG ≤2
• •* Organ Function: Serum direct bilirubin \<2 × ULN, AST/ALT ≤2.5 × ULN (up to 5 × ULN if due to liver involvement), CrCl ≥45 mL/min
• •* Other: Fully recovered from major surgery/acute toxic effects, effective contraception, written informed consent
• •2. ET Arm (High-Risk ET)
• •* Age: Adults ≥18 years
• •* Diagnosis: Confirmed ET (WHO 2016 criteria)
• •* High-Risk: At least one of:
• •* Age \>60 years
• •* Platelets \>1500 × 10⁹/L
• •* Prior thrombosis, erythromelalgia, or migraine (disease-related)
• •* Prior hemorrhage related to ET
• •* Diabetes/hypertension requiring therapy \>6 months
• •* Symptoms: ≥2 symptoms with average score ≥3 or total score ≥15 (MPN-SAF)
• •* Platelets: \>600 × 10⁹/L
• •* Resistant/Intolerant to HU: As defined by ELN
• •* Performance Status: ECOG ≤2
• •* Life Expectancy: \>24 weeks
• •* ANC: ≥1 × 10⁹/L
• •* Organ Function: Serum direct bilirubin \<2 × ULN, AST/ALT ≤2.5 × ULN, CrCl ≥45 mL/min
• •* Other: Fully recovered from major surgery/acute toxic effects, effective contraception, written informed consent