Anti-BCMA or/and Anti-CD19 CART Cells Treatment of Relapsed Multiple Myeloma

NCT03767725 | Unknown Phase 1

• 1 other identifier: Weihong Chen06082018
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial studies the side effects and best dose of BCMA CART cells in treating patients with BCMA positive multiple myeloma that have not respond to chemotherapy and autologous Hematopoietic Stem Cell Transplantation (Auto-HSCT). B-cell maturation antigen (BCMA), a cell surface protein expressed on mutiple maloma cells, has emerged as a very selective antigen to be targeted in novel immunotherpy for MM. Targeting postulated CD19 positive myeloma stem cells with anti-CD19 CAR-T cells is a novel approach to MM therapy.

Conditions

Multiple Myeloma in Relapse

Keywords

Anti-BCMA, Anti-CD19, CART cell, treatment, Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• No Dose-limiting toxicity

  No Dose-limiting toxicity

  up to 5 mouths after T cell infusion

Study Arms (1)

Treatment

EXPERIMENTAL

Phase 1 Clinical Study of The patients undergo leukapheresis. The patients then receive fludarabine and cyclophosphamide on days-5 to-3. Subjects will receive (0.6-60)x10E8 transduced CART cells as a split dose over three days as follows: Day 0, 10% fraction: (0.06-6)x10E8 CART19 cells, Day 1, 30% fraction: (0.18-18)x10E8 CART19 cells, Day 2, 60% fraction: (0.36-36)x10E8 CART19 cells.

Biological: Treatment

Interventions

Treatment BIOLOGICAL

Phase 1 Clinical Study of The patients undergo leukapheresis. The patients then receive fludarabine and cyclophosphamide on days-5 to-3. Subjects will receive (0.6-60)x10E8 transduced CART cells as a split dose over three days as follows: Day 0, 10% fraction: (0.06-6)x10E8 CART19 cells, Day 1, 30% fraction: (0.18-18)x10E8 CART19 cells, Day 2, 60% fraction: (0.36-36)x10E8 CART cells.

Treatment

Eligibility Criteria

• Age: 14 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Have the capacity to give informed consent
• Have measurable disease by International Myeloma Working Group (IMWG) criteria based on one or more of the following findings:
• Serum M-protein \>= 1 g/dL
• Urine M-protein \>= 200 mg/24 hour
• Involved serum free light chain (sFLC) level \>= 10 mg/dL with abnormal κ/λ ratio
• Measurable biopsy-proven plasmacytomas (\>= 1 lesion that has a single diameter \>= 2 cm)
• Bone marrow plasma cells \>= 30%
• Have a diagnosis of BCMA+ multiple myeloma (MM) (\>= 5% BCMA+ by flow cytometry on CD138 co-expressing plasma cells obtained within 45 days of study enrollment); the MM diagnosis must be confirmed by internal pathology review of a fresh biopsy specimen at the Fred Hutchinson Cancer Research Center (FHCRC)/Seattle Cancer Care Alliance (SCCA)
• Have relapsed or treatment refractory disease with \>= 10% CD138+ malignant plasma cells (IHC) on bone marrow (BM) core biopsy, either:
• Following autologous stem cell transplant (ASCT)
• Or, if a patient has not yet undergone ASCT, the individual must:
• Be transplant ineligible, due to age, comorbidity, patient choice, insurance reasons, concerns of rapidly progressive disease, and/or discretion of attending physician, and,
• Demonstrate disease that persists after \> 4 cycles of induction therapy and that is double refractory (persistence/progression) after therapy with both a proteasome inhibitor and immunomodulatory drug (IMiD) administered either in tandem, or in sequence.

You may not qualify if:

• Active hepatitis B, hepatitis C at the time of screening
• Patients who are (human immunodeficiency virus \[HIV\]) seropositive
• Subjects with uncontrolled systemic fungal, bacterial, viral or other infection despite appropriate antibiotics or other treatment at the time of leukapheresis
• \> 1 hospital admission for infection in prior 3 months
• Presence of acute or chronic graft-versus-host disease (GVHD) unless limited to skin involvement and managed with topical steroid therapy alone
• History of any one of the following cardiovascular conditions within the past 6 months: class III or IV heart failure as defined by the New York Heart Association (NYHA), cardiac angioplasty or stenting, myocardial infarction, unstable angina, or other clinically significant cardiac disease
• History or presence of clinically relevant central nervous system (CNS) pathology such as epilepsy, seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, psychosis, active central nervous system MM involvement and/or carcinomatous meningitis; subjects with previously treated central nervous systems involvement may participate, provided they are free of disease in the CNS (documented by flow cytometry performed on the cerebrospinal fluid (CSF) within one week of enrollment) and have no evidence of new sites of CNS activity
• Pregnant or nursing women; NOTE: Women of reproductive potential must have a negative serum pregnancy test performed within 48 hours of starting conditioning chemotherapy
• Use of any of the following:
• Therapeutic doses of corticosteroids (defined as \> 20 mg/day prednisone or equivalent) within 7 days prior to leukapheresis; physiologic replacement, topical, and inhaled steroids are permitted
• Allogeneic hematopoietic stem cell transplant (allo-HSCT) within 90 days of leukapheresis
• Cytotoxic chemotherapeutic agents within 1 week of leukapheresis; oral chemotherapeutic agents are allowed if at least 3 half-lives have elapsed prior to leukapheresis
• Low dose chemotherapy (e.g., bortezomib, lenalidomide, cyclophosphamide =\< 300 mg/m\^2) given after leukapheresis to maintain disease control must be stopped \>= 7 days prior to initiation of lymphodepleting chemotherapy
• Lymphotoxic chemotherapeutic agents within 2 weeks of leukapheresis
• Experimental agents within 4 weeks of leukapheresis unless progression is documented on therapy and at least 3 half-lives have elapsed prior to leukapheresis

Sponsors & Collaborators

• Shenzhen Second People's Hospital: lead

Study Sites (1)

Shenzhen Second People's Hospital,The first affiliated hospital of Shenzhen University

Shenzhen, Guangdong, 518035, China

RECRUITING

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Therapeutics

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Central Study Contacts

Weihong Chen, M.D.

CONTACT

86-755-83366388; whitney-cindy@hotmail.com

Xin Du, M.D.

CONTACT

86-755-83366388; duxingz@medmail.com.cn

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: professor, Chief physician, principal investigator

Model Details: Anti-BCMA or/and Anti-CD19 CAR Autologous T Cells

Study Record Dates

• First Submitted: December 5, 2018
• First Posted: December 7, 2018
• Study Start: June 2, 2018
• Primary Completion: June 1, 2021
• Study Completion: September 1, 2021
• Last Updated: December 10, 2018

Record last verified: 2018-12

Locations

CN (1)