A Feasibility and Safety Study of Concomitant Therapy With Allo-CAR-T Cells and Allo-HSCT in Patients With Relapse or Refractory Leukemia

NCT03463928 | Unknown Phase 1

• 1 other identifier: CHN-PLAGH-BT-027
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

Allogenic hematopoietic stem cell transplant (Allo-HSCT) is routinely used for treatment of aggressive hematological malignancies. The biological foundation of allo-HSCT is the graft-versus-leukemia (GVL) effect, which is primarily mediated by donor T cells present in the graft and is able to eradicate malignant B cells either CD19+ or CD19-. Relapse following an allo-HSCT remains a major challenge in the treatment of B-ALL. CD19-directed CAR-T cell therapy has shown promising results for the treatment of relapsed or refractory B-cell malignancies; however, a subset of patients relapse due to the loss of CD19 in tumor cells. Co-infusion of donor-derived CD19/22 bispecific CAR-T cells or CD19-directed CAR-T cells and donor-derived-HSCT has the potential to combine the CAR-T cell mediated targeted elimination of CD19 expressing B cells with GVL effect, which could have clear advantages in reducing the risk of relapse and the evolution of CD19- escape variants or clonally related malignancies in other lineages. Therefore, a complete and durable tumor responses induced by this immunotherapy could be expected.

Conditions

B Cell Leukemia

Outcome Measures

Primary Outcomes (1)

• Number of Participants with Severe/Adverse Events as a Measure of Safety and Tolerability

  24 weeks

Secondary Outcomes (3)

• Overall remission rate (ORR) = CR + CRi

  24 weeks

• Six-month Overall survival

  24 weeks

• Six-month Progression free survival

  24 weeks

Interventions

donor-derived CD19/22 bispecific CAR-T cells or CD19-directed CAR-T cells; donor-derived-HSCT BIOLOGICAL

The allo-CAR-T cells will be infused in a fractionated manner, 1/3 on day 0, 2/3 on day 1.The allo-HSCT will be infused on day 2.

Eligibility Criteria

• Age: 12 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Male or female participant
• Years to 60 Years
• Patient with relapsed or refractory B-cell leukemia or lymphoma
• Estimated life expectancy ≥ 12 weeks (according to investigator's judgement)
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
• Adequate organ function

You may not qualify if:

• Prior malignancy, except carcinoma in situ of the skin or cervix treated with curative intent and with no evidence of active disease
• Diagnosis of Burkitt's leukemia/lymphoma according to WHO classification or chronic myelogenous leukemia lymphoid blast crisis
• Richter's syndrome
• Presence of Grade II-IV (Glucksberg) or B-D (IBMTR) acute or extensive chronic GVHD at the time of screening
• Subjects with any autoimmune disease or any immune deficiency disease or other disease in need of immunosuppressive therapy
• Severe active infection (uncomplicated urinary tract infections, bacterial pharyngitis is allowed), Prophylactic antibiotic, antiviral and antifungal treatment is permissible
• Active hepatitis B, active hepatitis C, or any human immunodeficiency virus (HIV) infection at the time of screening
• Patient has an investigational medicinal product within the last 30 days prior to screening
• Previous treatment with investigational gene or cell therapy medicine products
• Pregnant or nursing women

Sponsors & Collaborators

• Chinese PLA General Hospital: lead

Study Sites (1)

Biotherapeutic Department and Hematology Department of Chinese PLA General Hospital

Beijing, 100853, China

RECRUITING

MeSH Terms

Conditions

Leukemia, B-Cell

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Central Study Contacts

Hejin Jia

CONTACT

86-10-55499341; jiahejin@163.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Molecular & Immunological Department, Biotherapeutic Department, Chinese PLA General Hospital

Study Record Dates

• First Submitted: March 7, 2018
• First Posted: March 13, 2018
• Study Start: October 8, 2017
• Primary Completion: June 1, 2019
• Study Completion: December 1, 2019
• Last Updated: March 13, 2018

Record last verified: 2018-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)