BCMA Chimeric Antigen Receptor Expressing T Cells in Multiple Myeloma

A Phase I Clinical Trial of T-Cells Targeting B-Cell Maturation Antigen for Subjects With BCMA-positive Multiple Myeloma

The goal of this clinical trial is to study the feasibility and efficacy of anti-B-Cell Maturation Antigen (BCMA) expressing T cells in treating patients with multiple myeloma.

Study Overview

• Status: Unknown
• Conditions: Multiple Myeloma
• Intervention / Treatment: Biological: Anti-BCMA CAR-T cells; Drug: Fludarabine; Drug: Cyclophosphamide

Detailed Description

Primary Objectives

1. To determine the feasibility ad safety of BCMA CAR-T cells in treating patients with multiple myeloma.
2. To determine in vivo dynamics and persistency of BCMA CAR-T cells.
3. To access the efficacy of BCMA CAR-T cells in patients with multiple myeloma.

Secondary Objectives

1. To assess the bone marrow and tumor migration of BCMA CAR-T cells.
2. To investigate the tumor killing capability of BCMA CAR-T cells in vitro
3. To investigate the possibility of host immune response to the mouse derived BCMA scFv, and evaluate its correlation to CAR-T persistence.
4. To correlate the subsets and differentiation of BCMA CAR-T cells to observed anti-tumor efficacy.

• Study Type: Interventional
• Enrollment (Anticipated): 10
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Henan
    • Zhengzhou, Henan, China
      • Recruiting
      • Henan Province of TCM

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Expected survival > 12 weeks
• Diagnosis of Multiple Myeloma by MWG criteria 20
• Patients previously received at least 3 different prior treatment regimens for multiple myeloma, including alkylating agent, protein inhibitors, and immunomodulator, and have disease progression in the past 60 days
• Important organs function enough to tolerate this therapy
• At least 90 days after stem cell transplantation
• Clinical performance status of ECOG score 0-4
• Accessible to intravenous injection, and no white blood cell collection contraindications
• Sexually active patients must be willing to utilize one of the more effective birth control methods for 30 days after the CTL infusion. Male partner should use a condom
• Able to understand and sign the Informed Consent Document.

Exclusion Criteria:

• Patients with symptoms of central nervous system
• Patients with second malignancies in addition to multiple myeloma
• Active hepatitis B or C, HIV infections
• Any other active diseases could affect the enrollment of this trial
• Suffering severe cardiovascular or respiratory disease
• Poorly controlled hypertension
• Long term use of immunosuppressive agents after organ transplantation, except currently receiving or recently received glucocorticoid treatment
• A history of mental illness and poorly controlled
• Screening showing target cell transduction efficacy is lower than 30%, or T cell proliferation is not enough for infusion (less than 5 fold)
• Occurrence of unstable pulmonary embolism, deep vein thrombosis, or other major arterial/venous thromboembolic events 30 days prior to assignment
• Women of child-bearing potential who are pregnant or breastfeeding during therapy, or have a planned pregnancy with 2 months after therapy
• Women of child-bearing potential who are not willing to practice birth control from the time of enrollment on this study and for 2 months after receiving the preparative regimen. Women of child bearing potential must have a negative serum or urine pregnancy test performed within 48 hours before infusion
• Active systemic infections or uncontrolled infection within 14 days prior enrollment
• Subjects suffering disease affects the understanding of informed consent or complying with study protocol

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: anti-BCMA CAR-T; Administration of anti-BCMA:TCRζ-4-1-BB CAR-T cells to patients with multiple myeloma	Biological: Anti-BCMA CAR-T cells; Retroviral vector-transduced autologous T cells to express anti-BCMA CAR; Drug: Fludarabine; dose: 25mg/m2/d; Drug: Cyclophosphamide; Dose: 40mg/kg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety measured by occurrence of study related adverse effects defined by NCI CTCAE 4.0	Safety measured by occurrence of study related adverse effects defined by NCI CTCAE 4.0	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall complete remission rate defined by the standard response criteria for malignant lymphoma for each arm	Overall complete remission rate defined by the standard response criteria for malignant lymphoma for each arm	8 weeks
Duration of CAR-positive T cells in circulation	Duration of CAR-positive T cells in circulation	6 months
Total number of CAR-positive T cells infiltrated into lymphoma tissue	Total number of CAR-positive T cells infiltrated into lymphoma tissue	6 months

Collaborators and Investigators

• Sponsor: The Second Affiliated Hospital of Henan University of Traditional Chinese Medicine
• Collaborators: First Affiliated Hospital of Wenzhou Medical University; Shanghai Changzheng Hospital; Hrain Biotechnology Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): February 15, 2017
• Primary Completion (Anticipated): September 1, 2019
• Study Completion (Anticipated): February 1, 2020

Study Registration Dates

• First Submitted: March 15, 2017
• First Submitted That Met QC Criteria: March 27, 2017
• First Posted (Actual): March 28, 2017

Study Record Updates

• Last Update Posted (Actual): February 27, 2019
• Last Update Submitted That Met QC Criteria: February 25, 2019
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Cyclophosphamide; Fludarabine
• Other Study ID Numbers: anti-BCMA CART

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No