Study of IFN-α Combined With CAR-T Cell Therapy in Relapsed and Refractory Acute Lymphoblastic Leukemia（R/R-ALL）

An Open-label, Phase 2, Single-Center Study to Assess the Efficacy and Safety of Interferon-α Combined With Chimeric Antigen Receptor (CAR) T-cell Therapy in Patients With Relapsed and Refractory Acute Lymphoblastic Leukemia（R/R-ALL)

The purpose of this study is to evaluate the safety and efficacy of IFN-α combined with CAR-T cell therapy in relapsed and refractory acute lymphoblastic leukemia (R/R ALL).

Study Overview

• Status: Recruiting
• Conditions: B-cell Acute Lymphoblastic Leukemia
• Intervention / Treatment: Combination product: IFN-α combined with CAR-T cell therapy

Detailed Description

This is a phase 2, single-center study. The patients will receive IFN-α combined with infusion of CAR T-cells in R/R B-ALL patients. The study participation will be 5 years including treatment and follow-up periods.

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: xiaowen tang, Ph.D; Phone Number: 1391353826; Email: xwtang1020@163.com
• Study Contact Backup: Name: depei wu, Ph.D; Phone Number: 86-0512677801856; Email: drwudepei@163.com

Study Locations

• China
  • Jiangsu
    • Suzhou, Jiangsu, China, 215000
      • Recruiting
      • The First Affiliated Hospital of Soochow University
      • Contact: xiaowen tang, doctor; Phone Number: 13913538266; Email: xwtang1020@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 65 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Diagnosed refractory and relapsed acute B-lymphoblastic leukemia.
2. Age 12-65.
3. Eastern Cooperative Oncology Group (ECOG) score 0-2.
4. Target on leukemia is >20% positive detected with flowcytometry.
5. Patients with left ventricular ejection fraction ≥ 0.5 by echocardiography or grade I/II cardiovascular dysfunction according to the New York Heart Association Classification.

5.Patients with aspartate aminotransferase or glutamic-pyruvic transaminase > 3x upper limit of normal or bilirubin > 2.0 mg/dL.

6.No other immunotherapy was received within 3 months.

Exclusion Criteria:

1. Patients are pregnant or lactating.
2. Patients with congenital immunodeficiency.
3. Patients with central nervous system leukemia.
4. Patients with uncontrolled active infection.
5. Patients with active hepatitis B or hepatitis C infection.
6. Patients with HIV infection.
7. Patients with atrial or venous thrombosis or embolism.
8. Patients with myo-infarction or severe arrythmia in the recent 6 months.
9. Other comorbidities that investigators considered not suitable for this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental group; IFN-α combined with CAR T-cells therapy	Combination product: IFN-α combined with CAR-T cell therapy; Adults: 14 daily intramuscular injections 300 million IU of Interferon-α for a 28-day cycle. Children: 14 daily intramuscular injections 200mg/m^2 of Interferon-α for a 28-day cycle. CAR T cell: (1-2)×10^7/kg, intravenously infusion.; Other Names: CAR-T cell therapy
No Intervention: Control group; CAR T-cells therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response rate (ORR)	ORR includes CR, CRi, MLFS and PR. Complete remission (CR)：Bone marrow blasts <5%; absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease; absolute neutrophil count >1.0x 10^9/L; platelet count >100x10^9/L. CR with incomplete hematologic recovery (CRi)：All CR criteria except for residual neutropenia (<1.0x10^9/L) or thrombocytopenia (<100x10^9/L). Morphologic leukemia-free state (MLFS): Bone marrow blasts <5%; absence of blasts with Auer rods; absence of extramedullary disease; no hematologic recovery required. Partial remission (PR): All hematologic criteria of CR; decrease of bone marrow blast percentage to 5% to 25%; and decrease of pretreatment bone marrow blast percentage by at least 50%.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of adverse events	adverse events are evaluated with CTCAE V5.0	2 years
Cumulative incidence of relapse(CIR)	time from the date of achievement of a remission until the date of relapse	2 years
Overall survival (OS)	time from enrollment to the date of death from any cause	2 years
Leukemia-free survival (LFS)	time from enrollment to the date of primary refractory disease, or relapse from CR, or death from any cause	2 years
the duration of CAR-T cells in patients	the time of CAR-T cells' persistence in blood and the copies of CAR-T cells	2 years

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital of Soochow University

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2019
• Primary Completion (Anticipated): July 31, 2023
• Study Completion (Anticipated): July 31, 2025

Study Registration Dates

• First Submitted: August 25, 2020
• First Submitted That Met QC Criteria: August 28, 2020
• First Posted (Actual): September 1, 2020

Study Record Updates

• Last Update Posted (Actual): September 1, 2020
• Last Update Submitted That Met QC Criteria: August 28, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Keywords: IFN-α, CAR-T
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid
• Other Study ID Numbers: IFN-α+CAR-T

Drug and device information, study documents

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