Eligibility Module
The Eligibility Module contains detailed information about who can participate in the clinical trial. This includes eligibility criteria, age restrictions, gender requirements, healthy volunteer status, and study population descriptions, helping researchers understand who is eligible to participate in the study.
Eligibility Module path is as follows:
Study -> Protocol Section -> Eligibility Module
Eligibility Module
Ignite Creation Date:
2025-12-25 @ 12:04 AM
Ignite Modification Date:
2025-12-25 @ 12:04 AM
NCT ID:
NCT02158858
Eligibility Criteria:
Phase I (Dose Escalation) - Inclusion and Exclusion Criteria:
1. Inclusion Criteria (Phase I):
* 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
2. Exclusion Criteria (Phase I):
* Untreated newly diagnosed acute leukemia (unless AML with myelodysplasia-related changes and 20-30% blasts)
* Relapsed/refractory acute leukemia where further induction chemotherapy is beneficial
* Acute leukemia relapse \<6 months after allogeneic SCT
* CML in blast crisis treated with only one TKI
* Very low/low risk MDS without prior treatment
* CNS involvement by leukemia (unless resolved)
* Active HIV, Hepatitis B or C infection
* GI impairment affecting absorption (unresolved nausea, vomiting, diarrhea \>CTCAE grade 1)
* Significant cardiac disease (recent MI/angina, high cTn, QTcF \>470 ms, LVEF \<50%, uncontrolled arrhythmia, etc.)
* Severe/uncontrolled comorbidities
* Recent systemic anti-cancer therapy (other than hydroxyurea/radiotherapy) \<2 weeks prior
* Ongoing or recent JAK inhibitor use (\<2 weeks prior, MF only)
* Recent therapeutic antibody (\<4 weeks) or investigational agent (\<2 weeks or \<5 half-lives)
* Use of strong CYP450 inhibitors/inducers or drugs with Torsades de Pointes risk
* Immunosuppressive treatment that cannot be discontinued
* Pregnant/lactating women
* Inadequate contraception
* Inability/unwillingness to comply with protocol
Phase II (Expansion) - Inclusion \& Exclusion Criteria:
1. Inclusion Criteria (Phase II):
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
2. Exclusion Criteria (Phase II)
* Prior splenectomy (MF non-TD cohorts)
* Splenic irradiation within 3 months
* Active or chronic HIV, Hepatitis B/C infection
* Active clinically significant infection (until recovery ≥2 weeks)
* Anemia deemed clinically significant (iron/B12/folate deficiency, hemolytic anemia)
* Major bleeding event (≥2 g/dL Hgb drop or ≥2 units transfused in last 6 months)
* Liver cirrhosis Child-Pugh B or C
* GI impairment affecting absorption (unresolved nausea, vomiting, diarrhea \>CTCAE grade 1)
* Rare hereditary problems of galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption (Arm 3)
* Hypersensitivity to ruxolitinib formulation (Arm 3)
* History of PML (Arm 3)
* Significant cardiac disease (recent MI/angina, QTcF \>500 ms \[\>450 ms in France/Germany\], uncontrolled arrhythmia, etc.)
* Ongoing uncontrolled hypertension
* Severe/uncontrolled comorbidities
* Systemic anticancer treatment (other than ruxolitinib for Arm 2, HU/ANA up to 24h prior) \<2 weeks or \<5 half-lives prior
* Prior treatment with any BET inhibitor
* Hematopoietic growth factor or androgenic steroids \<4 weeks prior
* Systemic corticosteroids ≥10 mg prednisone equivalent within 4 weeks (exceptions for short courses)
* Concurrent/second malignancy (except certain adequately treated cancers)
* Pregnant/lactating women, or planning pregnancy within protocol-defined window
* Inability/unwillingness to comply with protocol
Healthy Volunteers:
False
Sex:
ALL
Minimum Age:
18 Years
Study:
NCT02158858
Study Brief:
Protocol Section:
NCT02158858