Study of alloCART-19 Cell Therapy in Pediatric Patients With Relapsed/Refractory B-Cell Acute Lymphoblastic Leukemia

NCT04173988 | Active Not Recruiting Early Phase 1 DMC

• 1 other identifier: 2019-272
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the safety and tolerability of CD19-Directed Allogeneic Chimeric Antigen Receptor T- cell (alloCART-19)therapy in pediatric patients with relapsed/refractory acute lymphoblastic leukemia（ALL）.

Conditions

ALL, Childhood B-Cell

Keywords

Allogeneic CAR-T19

Outcome Measures

Primary Outcomes (1)

• Dose Limiting Toxicity

  Dose Limiting Toxicity (DLT) is defined as patients with the adverse event (AE) or laboratory abnormality per Lee DW and Locke FL standards and management guideline, and should be possibly related to alloCART-19 cell therapy, and should be unrelated to the disease itself, disease progression, concomitant diseases or concomitant medication. DLT will be analyzed as categorical variable，coded as 1 for DLT occur, 0 for no DLT.

  Day 28 after the first alloCART-19 infusion

Secondary Outcomes (3)

• The occurrence of adverse events

  After the first alloCART-19 infusion for 2 year

• Objective Response Rate

  Day 28 and 3 months after the first alloCART-19 infusion

• Best Overall Response

  Day 28 and 3 months after the first alloCART-19 infusion

Other Outcomes (2)

• AlloCART-19 cells

  After the first alloCART-19 infusion for 2 years

• T cell subsets

  After the first alloCART-19 infusion for 2 years

Study Arms (1)

alloCART-19

EXPERIMENTAL

For the very first patient, the initial dose could be administered via one or three intravenous infusions within 1 to 5 days. Starting from the second patient, the investigator will decide whether to use single or multiple alloCART-19 infusions, based on the treatment experience at previous dose level(s) and the patient's baseline disease burdens. A lymphodepletion conditioning with cyclophosphamide and fludarabine will be conducted before alloCART-19 infusion.

Genetic: alloCART-19; Drug: Cyclophosphamide; Drug: Fludarabine

Interventions

alloCART-19 GENETIC

AlloCART-19 is an allogeneic CAR-T cell product targeting CD19. * For children with body weight ≤ 50 kg, dose range for dose escalation will be 0.5 - 5 × 10\^6 CAR+ cells/kg * For children with body weight \> 50 kg, dose range for dose escalation will be 0.25 - 2.5 × 10\^8 CAR+ cells.

Also known as: allogeneic CAR-T19

alloCART-19

Cyclophosphamide DRUG

Chemotherapy for lymphodepletion

Also known as: no other intervention names

alloCART-19

Fludarabine DRUG

Chemotherapy for lymphodepletion

Also known as: no other intervention names

alloCART-19

Eligibility Criteria

• Age: 1 Year - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Signed informed consent and assent forms if applicable must be obtained prior to the start of any research procedure
• Age 1 year at the time of screening to age 18 years at the time of initial diagnosis
• Relapsed/refractory pediatric ALL that meet one of the following conditions:
• Incomplete patients with conventional chemotherapy regimens, or primary refractory patients who failed to complete remission with 2 courses of standard chemotherapy regimen, or did not achieve complete remission after first-line or multi-line salvage chemotherapy
• Early recurrence after complete remission (\< 12 months) or late recurrence after complete remission (≥ 12 months) and chemotherapy was not completely relieved by the standardized two course induction regimens
• Recurrence after autologous or allogeneic hematopoietic stem cell transplantation
• Patients who are Philadelphia chromosome-positive (Ph+) are eligible if they have failed at least 2 lines of chemotherapy and have failed two lines of TKI therapy or if TKI therapy is contraindicated.
• For relapsed patients, CD19 tumor expression demonstrated in bone marrow or peripheral blood by flow cytometry within 3 months of study entry
• Karnofsky performance status of \> 60 at screening
• During the screening period and within 10 days of treatment, adequate organ function defined as:
• Renal Function: serum creatinine ≤ 2 x ULN
• Liver Function: ALT and/or AST ≤ 10 x ULN (depending on age), bilirubin ≤ 5 x ULN
• Pulmonary Function: oxygen saturation ≥ 91%
• Heart Function: echocardiogram (ECHO): left ventricular ejection fraction (LVEF) ≥ 45%
• Bone marrow with ≥ 5% lymphoblasts by morphologic assessment at screening or immunological/molecular biological results with persistent MRD

You may not qualify if:

• Pregnant or lactating women
• Unable to tolerate venipuncture
• Prior history of:
• Allogeneic cell therapy (including hematopoietic stem cell transplantation) within 6 weeks of alloCART-19 infusion
• Any live vaccine within 4 weeks of alloCART-19 infusion and/or plan to receive live vaccine after enrollment
• Immunosuppressants for GvHD treatment within 4 weeks of alloCART-19 infusion
• Systemic corticosteroid treatment at doses greater than 5 mg/day prednisone\*3 days (or equivalent corticosteroids) within 72 hours prior to alloCART-19 treatment
• Before receiving alloCART-19 treatment, had received the following anti-neoplastic therapies: Tyrosine kinase inhibitors and hydroxyurea within 72 hours; Vincristine, 6-mercaptopurine, 6-thioguanine, methotrexate \< 25 mg/m2, cytosine arabinoside \< 100 mg/m2/day, or asparaginase (non-pegylated) within 1-week; Pegylated-asparaginase within 4 weeks; Central nervous system disease prophylaxis (e.g. intrathecal methotrexate) within 1 week; Investigational drug treatment within 4 weeks
• Had received the following anti-neoplastic radiotherapy before receiving alloCART-19 treatment: Radiotherapy for non-CNS sites within 2 weeks; Radiotherapy for the CNS site within 8 weeks
• Have the following medical history:
• Grade 2 to 4 acute or extensive chronic graft-versus-host disease (GVHD)
• Isolated extramedullary disease recurrence (e.g. central nervous system and testis)
• Previous or active central nervous system (CNS) diseases such as seizures, cerebral ischemia/bleeding, dementia, cerebellar disease or any autoimmune disease involving CNS
• Previous malignant tumors (excluding curative trends and inactive skin cancer in situ or cervical cancer)
• Genetic syndromes associated with bone marrow failure states: such as Fanconi anemia, Kostmann syndrome, Shwachman syndrome or any other known bone marrow failure syndrome (excluding Down syndrome)

Sponsors & Collaborators

• Children's Hospital of Fudan University: lead

Study Sites (1)

Children's Hospital of Fudan University

Shanghai, Minhang, 201102, China

Location

MeSH Terms

Interventions

Cyclophosphamide; fludarabine

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• zhai xiaowen, PhD

  PI

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: vice president

Study Record Dates

• First Submitted: November 13, 2019
• First Posted: November 22, 2019
• Study Start: January 9, 2020
• Primary Completion: October 20, 2024
• Study Completion: July 20, 2025
• Last Updated: March 15, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)