Health Condition 1: C910- Acute lymphoblastic leukemia [ALL]
Conditions
Interventions
Intervention1: Ruxolitinib drug: The drug will be administered at three different dose levels in total of 6 cohorts.
The drug will be added after phase I therapy (after 36 days post treatment).
Coho
Sponsors
Tata Research Administrative Council TRAC
Eligibility
Inclusion criteria
Inclusion criteria: 1. Newly diagnosed Ph-like B cell precursor acute lymphoblastic leukemia 2. Diagnostic bone marrow or peripheral blood sample must demonstrate a Ph-like expression profile with 1 of the following genetic lesions- a- CRLF2 overexpression by flow cytometry( >10%) b- CRLF2 rearrangement with fusion partners(IGH,P2RY8) or c- JAK2 rearrangement d- EPOR rearrangement e- PAX5 rearrangement f- Other JAK pathway alterations ( eg g, JAK2 fusions, EPOR fusions, SH2B3 deletions, IL7RA mutations) as detected by targeted RNA sequencing. 3. ECOG PS 0-3 4. Patients must have adequate organ and marrow function as defined below - Adequate liver function (SGOT/SGPT - Adequate kidney function (S. Cr 60ml/min/1.73m2) - Platelet count >75000/uL 5. Women of child bearing potential must agree to use adequate contraception prior to study entry and for the duration of study participation.
Exclusion criteria
Exclusion criteria: 1. Patients who test positive for Ph +ve (BCR-ABL 1) / ETV6-RUNX1 / TCF3-PBX1 / MLL rearrangements / High hyperdiploidy by FISH/Conventional karyotyping 2. Seropositivity (HIV)- Patients receiving anti-retroviral therapy 3. Active replication of Hepatitis B virus / Hepatitis C virus 4. Uncontrolled comorbidities (Hypertension / Diabetes Mellitus / Seizures) 5. Pregnant patients 6. Active uncontrolled infection 7. Usage of strong CYP3A4 inhibitors within 5 half lives before first dose of study drug
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Dose limiting toxicities at each level: 1.Grade 4 non-hematologic toxicity. 2.Grade 3 non-hematologic toxicity for greater than or equal to 7 consecutive days. 3. Grade greater than or equal to 2 serum bilirubin with coincident direct bilirubin greater than or equal to 0.5 mg/dL. 4.Any grade greater than or equal to 2 hemorrhagic event. 5.Grade 3 febrile neutropenia (At the discretion of investigator). 6.Grade 3/4 thrombocytopenia lasting for greater than or equal to 7 consecutive days.Timepoint: Twice weekly and/or at 64th day of phase II induction. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Pharmcokinetic parameters Like AUC, Cmax will be derived from the ruxolitinib concentrations present in their blood sample using Pheoneix WinNonlin software.Timepoint: 1 day;2. Event free survival will be calculated from date of enrolment in study to any event or last follow up. Events will be defined as relapse, progression, induction failure or death due to any cause. Kaplan â??Meier methodology will be used to calculate the event free survivalTimepoint: 2 years;3. Overall survival will be calculated from date of enrolment to death due to any cause. All patients will be censored at last follow up for survival analysis. 4. MRD negative rates (n subset of patients who are MRD positive at the time of enrolment)Timepoint: 2 years | — |
Countries
India
Contacts
Public ContactDr Hasmukh Jain
Tata Memorial Center
Outcome results
None listed