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

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

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.

Study Overview

• Status: Unknown
• Conditions: Acute T Cell Leukemia
• Intervention / Treatment: Drug: Ruxolitinib; Drug: Vincristine; Drug: Prednisone

• Study Type: Interventional
• Enrollment (Anticipated): 12
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Jie Ji, MD; Phone Number: 86-18980605802; Email: jieji@scu.edu.cn
• Study Contact Backup: Name: Ting Liu, MD; Phone Number: 86-28-85422370; Email: liuting@scu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 13 years to 75 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ruxolitinib, vincristine, prednisone; 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; Dose escalation up to 80 mg administered orally; Other Names: JAK1/JAK2 inhibitor; Drug: Vincristine; 1.4 mg/m2 i.v. weekly for 4 weeks; Other Names: Oncovin; Drug: Prednisone; 1 mg/kg orally 5 consecutive days per week for 4 weeks.; Other Names: steroid

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Sichuan University
• Investigators: Principal Investigator: Jie Ji, MD, West Chinia Hospital, Sichuan University

Study record dates

Study Major Dates

• Study Start (Anticipated): December 1, 2018
• Primary Completion (Anticipated): December 30, 2020
• Study Completion (Anticipated): March 30, 2021

Study Registration Dates

• First Submitted: July 16, 2018
• First Submitted That Met QC Criteria: August 1, 2018
• First Posted (Actual): August 3, 2018

Study Record Updates

• Last Update Posted (Actual): August 3, 2018
• Last Update Submitted That Met QC Criteria: August 1, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Leukemia, Lymphoid; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia; Leukemia, T-Cell; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Inflammatory Agents; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Phytogenic; Prednisone; Vincristine
• Other Study ID Numbers: HX-ETP-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No