Ruxolitinib Plus LVP in Patients With R/R ETP-ALL

Study Overview
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Brief Summary
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To determine the maximum tolerated dose (MTD), if present, and dose schedule of ruxolitinib in combination with L-ASP, vincristine, and prednisone (LVP) in patients with relapsed-and-refractory (R/R) early T precursor acute lymphocytic leukemia (ETP-ALL). Once determined, the purpose of this study will be to determine the efficacy of ruxolitinib in combination with LVP in patients with R/R ETP-ALL.

Official Title
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Phase I/II Study of Ruxolitinib Plus L-asparaginase, Vincristine, and Prednisone in Adult Patients With Relapsed or Refractory Early T Precursor Acute Lymphocytic Leukemia

Conditions
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Acute T Cell Leukemia

Intervention / Treatment
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* Drug: Ruxolitinib
* Drug: Vincristine
* Drug: Prednisone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects with early T-precursor ALL, with any of the following: refractory to primary induction therapy or refractory to salvage therapy, in untreated first relapse with first remission duration <12 months in untreated second or greater relapse relapse at any time after allogeneic HSCT Subject has received intensive combination chemotherapy for the treatment of ALL for initial treatment or subsequent salvage therapy. Greater than 5% blasts in the bone marrow Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 Exclusion Criteria: Malignancy other than ALL within 5 years before recruitment, except for adequately treated selected cancers without evidence of disease Current relevant central nervous system (CNS) pathology or known or suspected CNS involvement Isolated extramedullary disease Current autoimmune disease or history of autoimmune disease with potential CNS involvement Autologous HSCT within 6 weeks or allogeneic HSCT within 12 weeks before blinatumomab treatment, or eligibility for allogeneic HSCT at the time of enrollment Active acute grade 2 to 4 graft versus host disease (GvHD) according to Glucksberg et al (1974) criteria that required systemic treatment to prevent or treat GvHD 2 weeks before blinatumomab treatment Known exclusion criteria to investigator choice of SOC chemotherapy (per package insert) Cancer chemotherapy or radiotherapy with 2 weeks, or immunotherapy (included CD19 therapy) within 4 weeks of protocol-specified therapy Abnormal laboratory values (alanine or aspartate transaminase [ALT or AST] or alkaline phosphatase [ALP] ≥ 5 × upper limit of normal [ULN]; total bilirubin or creatinine ≥ 1.5 × ULN), or calculated creatinine clearance < 60 mL/min.

Ages Eligible for Study
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Minimum Age: 13 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Open label dosing cohorts will evaluate oral ruxolinitib (doses ranging from 10 - 80 mg) in combination with vincristine (1.4 mg/m2) and oral prednisone (1 mg/kg, 5 days a week for 4 weeks).
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ruxolitinib, vincristine, prednisone<br>Open label dosing cohorts will evaluate oral ruxolitinib (doses ranging from 10 - 80 mg) in combination with vincristine (1.4 mg/m2) and oral prednisone (1 mg/kg, 5 days a week for 4 weeks). | Drug: Ruxolitinib<br>* Dose escalation up to 80 mg administered orally<br>* Other names: JAK1/JAK2 inhibitor;Drug: Vincristine<br>* 1.4 mg/m2 i.v. weekly for 4 weeks<br>* Other names: Oncovin;Drug: Prednisone<br>* 1 mg/kg orally 5 consecutive days per week for 4 weeks.<br>* Other names: steroid;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Establish optimal dose of ruxolitinib | Determine maximum tolerated dose (MTD) of ruxolitinib | Upon completion of a 28 day treatment cycle | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate safety by assessing toxicities | Evaluate safety by assessing possible toxicities of thrombocytopenia, neutropenia, serum creatinine, total bilirubin, diarrhea, and/or vomiting. | Upon completion of a 28 day treatment cycle | 
| Overall response |  | At the end of Cycle 2 (each cycle is 60 days) | 
| Complete response |  | At the end of Cycle 2 (each cycle is 60 days) |