CD19-targeting CAR T Cells in Relapsed or Refractory CD19 Positive B-cell Malignancies

NCT03559439 | Unknown Phase 1

• 1 other identifier: PTA001
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single center, single arm, open-label phase 1 study to determine the safety and efficacy of autologous T cells expressing CD19 chimeric antigen receptors in adults with CD19+ B cell malignancies.

Conditions

B-cell Malignancy; B-cell Lymphoma; B-Cell Acute Lymphoblastic Leukaemia

Outcome Measures

Primary Outcomes (1)

• Frequency and severity of toxicities and adverse events

  To assess the frequency and severity of toxicities and adverse events according to NCI CTC v4.0

  24 weeks

Secondary Outcomes (2)

• overall response rate

  24 week

• overall survival

  24 week

Study Arms (1)

CD19 CAR T

EXPERIMENTAL

CD19 CAR T cells transduced with a lentiviral vector to express anti-CD19 scFv CD3z:CD28 administered by IV infusion.

Biological: CD19 CAR T

Interventions

CD19 CAR T BIOLOGICAL

CD19 CAR T cells transduced with a lentiviral vector to express anti-CD19 scFv CD3z:CD28 administered by IV infusion. Subjects will receive 0.1-10 x 10\^6 transduced CAR T cells as a split dose over three days as follows:Day 1, 10% fraction, Day 2, 30% fraction, Day 3, 60% fraction.

CD19 CAR T

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• CD19+ relapsed or refractory B cell malignancies:
• Relapsed or refractory B acute lymphocytic leukemia.
• Relapse was defined as presence of \> 5% blasts at screening, or second or subsequent bone marrow relapse, or any bone marrow relapse after allogeneic stem cell transplant and must be ≥ 6 months from stem cell transplant at the time of infusion.
• Refractory was defined by not achieving an initial complete response after 2 cycles of a standard chemotherapy regimen . Patients who were refractory to subsequent chemotherapy regimens after an initial remission were considered chemorefractory
• Patients with Ph+ acute lymphocytic leukemia were eligible if they are intolerant to or have not achieved a remission after two lines of tyrosine kinase inhibitor therapy, or if tyrosine kinase inhibitor therapy is contraindicated, or ineligible for allogeneic stem cell transplant because of:
• Comorbid disease
• Other contraindications to allogeneic stem cell transplant conditioning regimen
• Lack of suitable donor
• Prior hematopoietic stem cell transplant
• Declined allogeneichematopoietic stem cell transplant as a therapeutic option
• Relapsed or refractory non-Hodgkin's lymphoma
• Histopathological CD19+.
• No response to last line of therapy i. partial response as best response to most recent therapy regimen ii. partial response as best response to most recent therapy with duration no longer than 6 month from last dose of therapy
• Refractory post-Autologous stem cell transplant i. Disease progression or relapsed less than or equal to 12 months of Autologous stem cell transplant (must have biopsy proven recurrence in relapsed subjects) ii. If salvage therapy is given post-Autologous stem cell transplant, the subject must have had no response to or relapsed after the last line of therapy
• Subjects must have received adequate prior therapy including at a minimum: anti-CD20 monoclonal antibody unless investigator determines that tumor is CD20-negative and an anthracycline containing chemotherapy regimen for subjects with transformed follicular lymphoma must have received prior chemotherapy for follicular lymphoma and subsequently have chemorefractory disease after transformation to Diffuse large B-cell lymphoma

You may not qualify if:

• Isolated extra-medullary relapse leukemia
• Other malignancies
• Concomitant genetic syndrome, with the exception of Down Syndrome
• Burkitt's lymphoma/leukemia
• Treatment with any prior gene therapy product, anti-CD19/anti-CD3 therapy, or any other anti-CD19 therapy
• Active hepatitis B, C, or any uncontrolled infection
• Grade 2 to 4 Graft versus Host Disease (GVHD)
• Medications or treatments that were to be excluded:
• Corticosteroids within 72 hours of infusion, with the exception of physiologic replacement
• Allogeneic cellular therapy, such as donor lymphocyte infusion within 6 weeks prior to infusion
• Graft versus Host Disease therapies
• Chemotherapy stopped prior to lymphodepletion based on clearance
• central nervous system prophylaxis treatment
• Active central nervous system disease (central nervous system 2 disease \[Cerebral spinal fluid containing blasts, but \< 5 WBCs/microliter\] patients were eligible)
• Any condition that investigator considered may increase the risk of the subjects or interfere with the trial results

Sponsors & Collaborators

• Shanghai Tong Ren Hospital: lead
• Gracell Biotechnology Ltd.: collaborator

Study Sites (1)

Shanghai Tong Ren hospital

Shanghai, China

RECRUITING

MeSH Terms

Conditions

Lymphoma, B-Cell; Burkitt Lymphoma

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections

Study Officials

• Ligen Liu

  Shanghai Tong Ren Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ligen Liu

CONTACT

18017337037; llg3532@shtrhospital.com

Study Design

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

Study Record Dates

• First Submitted: May 30, 2018
• First Posted: June 18, 2018
• Study Start: April 24, 2018
• Primary Completion: November 30, 2021
• Study Completion: December 31, 2021
• Last Updated: November 5, 2020

Record last verified: 2020-11

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)