CD19 Targeted CAR T Cell Therapy in Patients With Relapsed/ Refractory B Cell Acute Lymphoblastic Leukaemia (ALL)

NCT ID: NCT04653493

Last Updated: 2021-03-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

UNKNOWN

Clinical Phase

PHASE1

Total Enrollment

22 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-08-31

Study Completion Date

2024-08-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

This is a single-arm, open-label, phase I study (safety and dose escalation) of autologous Chimeric Antigen Receptor (CAR) T-cells targeting CD19 in patients with relapsed/refractory B cell acute lymphoblastic leukemia (ALL).

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

In this single-center, open-label, nonrandomized, no control, prospective clinical trial, pediatric or adolescent/young adult patients with CD19+ relapsed or refractory B cell acute lymphoblastic leukemia (R/R B-ALL) will be enrolled.

Eligible patients will receive CAR T product intravenously as a single or split dose following pre-conditioning by a lymphodepleting chemotherapeutic regimen and will then enter a 30-day follow-up period to monitor adverse events using the NCI CTCAE (version 5.0).

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Relapsed B Cell Acute Lymphoblastic Leukemia (ALL) Refractory B Cell Acute Lymphoblastic Leukemia (ALL)

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

CD19 CAR-T cells

Pediatric or adolescent/young adult patients with CD19+ relapsed or refractory B cell acute lymphoblastic leukemia (R/R B-ALL)

Group Type EXPERIMENTAL

CD19 CAR engineered autologous T-cells

Intervention Type BIOLOGICAL

Given IV

Following preconditioning with lymphodepleting chemotherapy (cyclophosphamide and fludarabine) patients will be treated with CD19 Chimeric Antigen Receptor (CAR) T cells as a single or split dose (day 0, 1 and 2, CAR cells will be intravenously infused at the 10%, 30% and 60% ratio respectively). Dosing of CD19 CAR-T cells will follow a dose-escalation schema, with dose changes based on dose-limiting toxicities.

Cyclophosphamide

Intervention Type DRUG

Given IV

Fludarabine

Intervention Type DRUG

Given IV

Mesna

Intervention Type DRUG

Given IV

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

CD19 CAR engineered autologous T-cells

Given IV

Following preconditioning with lymphodepleting chemotherapy (cyclophosphamide and fludarabine) patients will be treated with CD19 Chimeric Antigen Receptor (CAR) T cells as a single or split dose (day 0, 1 and 2, CAR cells will be intravenously infused at the 10%, 30% and 60% ratio respectively). Dosing of CD19 CAR-T cells will follow a dose-escalation schema, with dose changes based on dose-limiting toxicities.

Intervention Type BIOLOGICAL

Cyclophosphamide

Given IV

Intervention Type DRUG

Fludarabine

Given IV

Intervention Type DRUG

Mesna

Given IV

Intervention Type DRUG

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

CD19+ ALL patients with any of the following:

1. Relapsed or Refractory CD19 positive B-cell acute lymphoblastic leukemia (R/R B-ALL) A. Primary refractory disease despite at least 2 cycles of an intensive chemotherapy regimen designed to induce remission B. Refractory disease despite salvage therapy C. 2nd or greater relapse D. Any relapse after allogeneic hematopoietic stem cell transplantation
2. Informed consent explained to and signed by patient/parents or legal guardian.
3. The Karnofsky (age ≥10 years)/Lansky (age \<10 years) performance status score over 50 points.
4. Expected to survive for more than 3 months.
5. Patients with a history of prior allogeneic hematopoietic stem cell transplant (HSCT) must be at least 3 months from HSCT at the time of CD19 CAR-T cells infusion and also have not received a donor lymphocyte infusion (DLI) within the 28 days prior to apheresis.
6. Important organ function is satisfied: Heart ultrasound indicates cardiac ejection fraction ≥ 50%, no obvious abnormality in ECG; Adequate pulmonary function defined as forced vital capacity (FVC) ≥ 50% of predicted value; or pulse oximetry ≥ 92% on room air if the patient is unable to perform pulmonary function testing; creatinine clearance calculated by Cockcroft-Gault formula ≥ 50 ml/min/1.73m2; Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤ 5 times the upper limit of normal for age; Total Bilirubin ≤ 3 times the upper limit of normal for age.
7. Absolute lymphocyte count ≥ 0.5 x 10⁹/L.
8. Hemoglobin ≥ 8 g/dl (can be transfused).
9. Platelet count ≥ 20,000/μL (can be transfused).
10. Meets eligibility criteria to undergo autologous apheresis.

Exclusion Criteria

1. Isolated extra-medullary disease relapse.
2. Active CNS involvement of ALL (CNS Grade 3 per National Comprehensive Cancer Network guidelines).
3. Severe, uncontrolled bacterial, fungal or viral infections (Active hepatitis B or C, history of HIV infection)
4. Pre-existing significant neurological disorder.
5. Active significant acute graft versus host disease (GVHD) or moderate/severe chronic GVHD requiring systemic steroids or other immunosuppressants within 4 weeks of enrolment.
6. Pregnant or lactating female.
7. The patient did not agree to use effective contraception during the treatment period and for the following 1 year.
8. A history of other malignant tumors.
9. Receiving systemic steroids therapy exceeding the equivalent of 0.5 mg/ kg/day of methylprednisolone, in the 7 days prior to CAR T-cell infusion
10. Receiving systemic immunosuppressive therapy in the 14 days prior to CAR T-cell infusion
11. Receiving intrathecal chemotherapy in the 7 days prior to CAR T-cell infusion
Maximum Eligible Age

25 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Gene Therapy Research Center, Shariati Hospital, Tehran University of Medical Sciences, Iran

UNKNOWN

Sponsor Role collaborator

Research Institute for Oncology- Hematology and Cell Therapy (RIOHCT), Tehran University of Medical Sciences, Iran

UNKNOWN

Sponsor Role collaborator

Sabz Biomedicals

INDUSTRY

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Tahereh Rostami, M.D

Role: PRINCIPAL_INVESTIGATOR

Research Institute for Oncology- Hematology and Cell Therapy (RIOHCT), Tehran University of Medical Sciences, Tehran, Iran

Naser Ahmadbeigi, PhD

Role: STUDY_DIRECTOR

Gene Therapy Research Center, Shariati hospital, Tehran University of Medical Sciences, Tehran, Iran

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Gene therapy research center, Shariati hospital, Tehran university of medical sciences, Iran

Tehran, , Iran

Site Status

Research Institute for Oncology- Hematology and Cell Therapy (RIOHCT), Tehran University of Medical Sciences

Tehran, , Iran

Site Status

Countries

Review the countries where the study has at least one active or historical site.

Iran

Central Contacts

Reach out to these primary contacts for questions about participation or study logistics.

Tahereh Rostami, M.D

Role: CONTACT

+9821-88004140

Naser Ahmadbeigi, PhD

Role: CONTACT

+9821-82415103

Facility Contacts

Find local site contact details for specific facilities participating in the trial.

Naser Ahmadbeigi, Phd

Role: primary

+9821-82415103

Tahereh Rostami, M.D

Role: primary

+982188004140

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

CD19 CAR T Cells for R/R ALL

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.

CD4CAR for CD4+ Leukemia and Lymphoma
NCT03829540 RECRUITING PHASE1
CAR-T Cell Therapy Targeting to CD19 for R/R ALL
NCT03919240 ACTIVE_NOT_RECRUITING PHASE1/PHASE2