Clinical Trial to Evaluate the Safety and Efficacy of IM19 CAR-T Cells in Patients With Relapsed and Refractory (R/R) B-cell Acute Lymphoblastic Leukemia

A Phase 1-2 Study to Evaluate the Safety and Efficacy of IM19 CAR-T Cells in Patients With Relapsed and Refractory (R/R) B-cell Acute Lymphoblastic Leukemia

This is a phase I/II, open-label, multicenter study to assess the efficacy and safety of IM19 CAR-T cells in R/R B-cell Acute Lymphoblastic Leukemia

Study Overview

• Status: Not yet recruiting
• Conditions: Leukemia
• Intervention / Treatment: Biological: IM19 CAR-T cells

• Study Type: Interventional
• Enrollment (Anticipated): 58
• Phase: Phase 2; Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 25 years (ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Relapsed or refractory B-ALL, defined as:

  1. Not chieving a CR after 1 cycle of standard chemotherapy for relapsed leukemia.
  2. Any relapse after HSCT and must be ≥ 6 months from HSCT at the time of IM19 CAR-T cells infusion.
  3. Primary refractory as defined by not achieving a CR after 2 cycles of a standard chemotherapy regimen.
• Patients with Ph+ ALL are eligible if they are intolerant to or have failed two lines of TKI ± chemotherapy ；Ph + all patients with T315I mutation are not required to receive at least two TKI ± chemotherapy in the absence of effective TKI therapy;
• Morphological evidence of disease in bone marrow (at least 5% blasts).
• Aged 3 to 25 years, either sex;
• Estimated life expectancy >3 months;
• ECOG performance status of 0 or 1(age ≥ 16 years) or Lansky (age < 16 years) performance status ≥ 50;
• Women of childbearing age who had a negative blood pregnancy test before the start of the trial and agreed to take effective contraceptive measures during the trial period until the last follow-up; male subjects with fertility partners agreed to take effective contraceptive measures during the trial period until the last follow-up;
• Adequate organ function;
• Volunteer to participate in this trial and sign on the informed consent.

Exclusion Criteria:

• Isolated extramedullary disease relapse；
• Burkitt's lymphoma；
• Patient has obvious symptoms of central nervous system invasion and needs targeted treatment;
• Patient has previously received gene product therapy;
• Patients have graft-versus-host response（GVHD） and need to use immunosuppressants; Or GVHD ≥ grade 2 or being treated with anti GVHD; Or suffering from autoimmune diseases;
• Patient received chemotherapy or radiotherapy within 3 days before leukapheresis
• Patient used systemic steroids within 5 days before leucapheresis, except those who were recently or currently using inhaled steroids;
• Patients who used drugs to stimulate the production of bone marrow hematopoietic cells within 5 days before leucapheresis;
• Patients have participated in other clinical studies within 1 month before screening or plan to participate in other drug clinical trials during this study;
• Patient received allogeneic cell therapy within 6 weeks before CAR-T cell infusion, such as donor lymphocyte infusion(DLI)；
• History or presence of CNS disorder, such as epilepsy, epileptic seizures, cerebrovascular disease (ischemia / hemorrhage / cerebral infarction), brain edema, reversible posterior white matter encephalopathy, paralysis, aphasia, stroke, severe brain injury, dementia, Parkinson's disease, cerebellar disease, cerebral organic syndrome or mental disease;
• Patients has HBV, HCV, HIV ,EBV,ECV or syphilis infection at the time of screening;
• Pregnant or lactating, or planning pregnancy within 180 days after the end of CAR-T cells infusion, or male patients whose partners plan pregnancy 180 days after their CAR-T cell infusion;
• Patients with other tumors in the past 5 years;
• Within 14 days before enrollment, there were active or uncontrollable infections requiring systemic treatment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SEQUENTIAL
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: IM19 CAR-T cells	Biological: IM19 CAR-T cells; IM19 CAR-T cells will be administered at dose level:5 x 10^4 CAR+ T cells/kg,1x 10^5 CAR+ T cells/kg,3 x 10^5 CAR+ T cells/kg,1 x 10^6 CAR+ T cells/kg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Treatment Related adverse events (AEs)		Up to 28 days after CAR-T cell infusion
Persistence of CAR-T cells (cell counts and cell percentage in peripheral blood and bone marrow)	The persistence over time of CAR T cells in the peripheral blood as determined by flow cytometry and qPCR.	Up to 24 weeks after CAR-T cell infusion

Secondary Outcome Measures

Outcome Measure	Time Frame
Objective response rate (ORR)	At 28 days, 3 months and 6 months after CAR-T cell infusion
Anti-therapeutic IM19 CAR-T cells antibody	Up to 24 weeks after CAR-T cell infusion

Collaborators and Investigators

• Sponsor: Beijing Immunochina Medical Science & Technology Co., Ltd.
• Investigators: Principal Investigator: Qian Jiang, Peking University People's Hospital

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): April 1, 2022
• Primary Completion (ANTICIPATED): April 1, 2025
• Study Completion (ANTICIPATED): June 1, 2025

Study Registration Dates

• First Submitted: March 25, 2022
• First Submitted That Met QC Criteria: March 25, 2022
• First Posted (ACTUAL): April 4, 2022

Study Record Updates

• Last Update Posted (ACTUAL): April 4, 2022
• Last Update Submitted That Met QC Criteria: March 25, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: CAR-T; B-cell Acute Lymphoblastic Leukemia
• 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: SD3

Drug and device information, study documents

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