search
Back to results

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

Primary Purpose

ALL, Childhood B-Cell

Status
Recruiting
Phase
Early Phase 1
Locations
China
Study Type
Interventional
Intervention
alloCART-19
Cyclophosphamide
Fludarabine
Sponsored by
Children's Hospital of Fudan University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for ALL, Childhood B-Cell focused on measuring Allogeneic CAR-T19

Eligibility Criteria

1 Year - 18 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria

  • 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:

    1. 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
    2. 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
    3. 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:

    1. Renal Function: serum creatinine ≤ 2 x ULN
    2. Liver Function: ALT and/or AST ≤ 10 x ULN (depending on age), bilirubin ≤ 5 x ULN
    3. Pulmonary Function: oxygen saturation ≥ 91%
    4. 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
  • Female subjects of childbearing age must have a negative serum or urine pregnancy test during the screening period and agree to take effective contraceptive measures during the trial period until the last follow-up

Exclusion Criteria

  • Pregnant or lactating women
  • Unable to tolerate venipuncture
  • Prior history of:

    1. Allogeneic cell therapy (including hematopoietic stem cell transplantation) within 6 weeks of alloCART-19 infusion
    2. Any live vaccine within 4 weeks of alloCART-19 infusion and/or plan to receive live vaccine after enrollment
    3. Immunosuppressants for GvHD treatment within 4 weeks of alloCART-19 infusion
    4. Systemic corticosteroid treatment at doses greater than 5 mg/day prednisone*3 days (or equivalent corticosteroids) within 72 hours prior to alloCART-19 treatment
    5. 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
    6. 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:

    1. Grade 2 to 4 acute or extensive chronic graft-versus-host disease (GVHD)
    2. Isolated extramedullary disease recurrence (e.g. central nervous system and testis)
    3. Previous or active central nervous system (CNS) diseases such as seizures, cerebral ischemia/bleeding, dementia, cerebellar disease or any autoimmune disease involving CNS
    4. Previous malignant tumors (excluding curative trends and inactive skin cancer in situ or cervical cancer)
    5. 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)
    6. Active or latent hepatitis B or active hepatitis C (test within 8 weeks of screening period)
    7. History of HIV, or HIV-positive test within 8 weeks of screening period
    8. Any uncontrolled serious infection during the screening period
    9. Severe, poorly controlled concomitant diseases such as, but not limited to, nervous system, kidney, liver, endocrine or gastrointestinal disorders that may be deemed by the investigator to interfere with the inclusion of the subject in the study.
    10. Any clinical abnormalities including but not limited to the nervous system, cardiovascular system, blood and lymphatic system, immune system, kidney, liver, gastrointestinal tract, respiratory system, metabolism and bones that may be deemed by the investigator to interfere with the inclusion of a subject in the study.
  • The following treatments and/or medications must be excluded:

    1. Simultaneous application of other anti-neoplastic drugs, including traditional Chinese herbal medicines
    2. Drugs that prolong the QT interval (including Ia and III antiarrhythmic drugs)
    3. Daily oxygen therapy
    4. long-term use of corticosteroids (except for inhaled and topical use)
  • Any circumstance or condition that in the judgement of the investigator may interfere with the subject's participation in the trial.

Sites / Locations

  • Children's Hospital of Fudan UniversityRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

alloCART-19

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

The occurrence of adverse events
The adverse events (AE) is a composite variable including liver and kidney function damage, nausea, vomiting, arrhythmia and dyspnea. The variable would be coded as 1 if any of these events occurs after the first alloCART-19 infusion while 0 for none . These adverse events would be measured by assessment scale method according to NCI CTC AE v5.0 classification standard.
Objective Response Rate
Objective Response Rate(ORR)is defined as the proportion of patients whose tumor volume shrank to a predetermined value and the minimum time limit required. ORR = complete remission (CR) + incomplete complete remission (CRi)
Best Overall Response
Best Overall Response(BOR)at 28 days and 3 months after drug infusion was evaluated to preliminarily evaluate the optimal efficacy of alloCART-19 infusion in patients.

Full Information

First Posted
November 13, 2019
Last Updated
November 12, 2022
Sponsor
Children's Hospital of Fudan University
search

1. Study Identification

Unique Protocol Identification Number
NCT04173988
Brief Title
Study of alloCART-19 Cell Therapy in Pediatric Patients With Relapsed/Refractory B-Cell Acute Lymphoblastic Leukemia
Official Title
A Single Center, Open Label, Single Arm Exploratory Clinical Study of CD19-Directed Allogeneic Chimeric Antigen Receptor CART-cell Immunotherapy Cell Therapy in Pediatric Patients With Relapsed/Refractory B-Cell Acute Lymphoblastic Leukemia
Study Type
Interventional

2. Study Status

Record Verification Date
November 2022
Overall Recruitment Status
Recruiting
Study Start Date
January 9, 2020 (Actual)
Primary Completion Date
October 20, 2023 (Anticipated)
Study Completion Date
July 20, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Children's Hospital of Fudan University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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).
Detailed Description
This is a single center, open label, single arm, dose escalation study to explore the safety, tolerability, and pharmacokinetic / pharmacodynamic profile of CD19-Directed Allogeneic Chimeric Antigen Receptor T- cell (alloCART-19) in pediatric patients with relapsed or refractory B-cell acute lymphoblastic leukemia. The study will also assess the preliminary efficacy of CD19-Directed Allogeneic Chimeric Antigen Receptor T- cell (alloCART-19). For this exploratory clinical trial, approximately 3-6 patients will be enrolled. During dose escalation, at least one evaluable patient will be enrolled at each dose level. Once DLT is reached, 1 to 3 additional patients will be enrolled at the dose level below DLT, which has been tested and determined to be safe in the trial, to evaluate the optimal safe and therapeutic dose to be approved by the investigator and sponsor.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
ALL, Childhood B-Cell
Keywords
Allogeneic CAR-T19

7. Study Design

Primary Purpose
Treatment
Study Phase
Early Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
6 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
alloCART-19
Arm Type
Experimental
Arm Description
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.
Intervention Type
Genetic
Intervention Name(s)
alloCART-19
Other Intervention Name(s)
allogeneic CAR-T19
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Other Intervention Name(s)
no other intervention names
Intervention Description
Chemotherapy for lymphodepletion
Intervention Type
Drug
Intervention Name(s)
Fludarabine
Other Intervention Name(s)
no other intervention names
Intervention Description
Chemotherapy for lymphodepletion
Primary Outcome Measure Information:
Title
Dose Limiting Toxicity
Description
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.
Time Frame
Day 28 after the first alloCART-19 infusion
Secondary Outcome Measure Information:
Title
The occurrence of adverse events
Description
The adverse events (AE) is a composite variable including liver and kidney function damage, nausea, vomiting, arrhythmia and dyspnea. The variable would be coded as 1 if any of these events occurs after the first alloCART-19 infusion while 0 for none . These adverse events would be measured by assessment scale method according to NCI CTC AE v5.0 classification standard.
Time Frame
After the first alloCART-19 infusion for 2 year
Title
Objective Response Rate
Description
Objective Response Rate(ORR)is defined as the proportion of patients whose tumor volume shrank to a predetermined value and the minimum time limit required. ORR = complete remission (CR) + incomplete complete remission (CRi)
Time Frame
Day 28 and 3 months after the first alloCART-19 infusion
Title
Best Overall Response
Description
Best Overall Response(BOR)at 28 days and 3 months after drug infusion was evaluated to preliminarily evaluate the optimal efficacy of alloCART-19 infusion in patients.
Time Frame
Day 28 and 3 months after the first alloCART-19 infusion
Other Pre-specified Outcome Measures:
Title
AlloCART-19 cells
Description
AlloCART-19 cells would be detected in peripheral blood, bone marrow, and/or CSF. The variable would be coded as 1 if any alloCART-19 cell was founded in the tissues metioned above while 0 for none.
Time Frame
After the first alloCART-19 infusion for 2 years
Title
T cell subsets
Description
T cell subsets is a composite varible including CD3, CD4 and CD8 ratio observed in blood and bone marrow. The variable would be coded as 1 if any of these observations were not in normal range while 0 for all normal.
Time Frame
After the first alloCART-19 infusion for 2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
1 Year
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria 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 Female subjects of childbearing age must have a negative serum or urine pregnancy test during the screening period and agree to take effective contraceptive measures during the trial period until the last follow-up Exclusion Criteria 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) Active or latent hepatitis B or active hepatitis C (test within 8 weeks of screening period) History of HIV, or HIV-positive test within 8 weeks of screening period Any uncontrolled serious infection during the screening period Severe, poorly controlled concomitant diseases such as, but not limited to, nervous system, kidney, liver, endocrine or gastrointestinal disorders that may be deemed by the investigator to interfere with the inclusion of the subject in the study. Any clinical abnormalities including but not limited to the nervous system, cardiovascular system, blood and lymphatic system, immune system, kidney, liver, gastrointestinal tract, respiratory system, metabolism and bones that may be deemed by the investigator to interfere with the inclusion of a subject in the study. The following treatments and/or medications must be excluded: Simultaneous application of other anti-neoplastic drugs, including traditional Chinese herbal medicines Drugs that prolong the QT interval (including Ia and III antiarrhythmic drugs) Daily oxygen therapy long-term use of corticosteroids (except for inhaled and topical use) Any circumstance or condition that in the judgement of the investigator may interfere with the subject's participation in the trial.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Zhai xiaowen, PhD
Phone
8618017590808
Email
zhaixiaowendy@163.com
First Name & Middle Initial & Last Name or Official Title & Degree
wang hongsheng, PhD
Phone
8613916453373
Email
hongsheng@hotmail.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
zhai xiaowen, PhD
Organizational Affiliation
PI
Official's Role
Study Director
Facility Information:
Facility Name
Children's Hospital of Fudan University
City
Shanghai
State/Province
Minhang
ZIP/Postal Code
201102
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Qian Xiaowen, Master
Phone
8613636405337
Email
qxw08@hotmail.com
First Name & Middle Initial & Last Name & Degree
Wang hongsheng, PHD
First Name & Middle Initial & Last Name & Degree
Cao Ping, master
First Name & Middle Initial & Last Name & Degree
Shen Chen, bachelor

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

We'll reach out to this number within 24 hrs