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

Phase 1
Conditions
Acute T Cell Leukemia
Interventions
Registration Number
NCT03613428
Lead Sponsor
Sichuan University
Brief Summary

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.

Detailed Description

Not available

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
12
Inclusion Criteria
  1. 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
  2. Subject has received intensive combination chemotherapy for the treatment of ALL for initial treatment or subsequent salvage therapy.

  3. Greater than 5% blasts in the bone marrow

  4. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2

Exclusion Criteria
  1. Malignancy other than ALL within 5 years before recruitment, except for adequately treated selected cancers without evidence of disease
  2. Current relevant central nervous system (CNS) pathology or known or suspected CNS involvement
  3. Isolated extramedullary disease
  4. Current autoimmune disease or history of autoimmune disease with potential CNS involvement
  5. Autologous HSCT within 6 weeks or allogeneic HSCT within 12 weeks before blinatumomab treatment, or eligibility for allogeneic HSCT at the time of enrollment
  6. 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
  7. Known exclusion criteria to investigator choice of SOC chemotherapy (per package insert)
  8. Cancer chemotherapy or radiotherapy with 2 weeks, or immunotherapy (included CD19 therapy) within 4 weeks of protocol-specified therapy
  9. 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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
ruxolitinib, vincristine, prednisonePrednisoneOpen 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).
ruxolitinib, vincristine, prednisoneRuxolitinibOpen 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).
ruxolitinib, vincristine, prednisoneVincristineOpen 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).
Primary Outcome Measures
NameTimeMethod
Establish optimal dose of ruxolitinibUpon completion of a 28 day treatment cycle

Determine maximum tolerated dose (MTD) of ruxolitinib

Secondary Outcome Measures
NameTimeMethod
Overall responseAt the end of Cycle 2 (each cycle is 60 days)
Evaluate safety by assessing toxicitiesUpon completion of a 28 day treatment cycle

Evaluate safety by assessing possible toxicities of thrombocytopenia, neutropenia, serum creatinine, total bilirubin, diarrhea, and/or vomiting.

Complete responseAt the end of Cycle 2 (each cycle is 60 days)
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