Study of T Cells Targeting CD138/BCMA/CD19/More Antigens (CART-138/BCMA/19/More) for Chemotherapy Refractory and Relapsed Multiple Myeloma

Placing a tumor antigen chimeric receptor that has been created in the laboratory into patient autologous or donor-derived T cells may make the body build immune response to kill cancer cells. Genetically engineered lymphocyte (CART) therapy has showed good safety and efficacy in treatment of lymphoma and acute lymphoblastic leukemia. Researchers want to see if this helps people with multiple myeloma.To test the safety and efficacy of giving targeting CD138 or B-cell maturation antigen or CD19 or more antigens T cells in treating patients with multiple myeloma that is refractory to further chemotherapy or relapsed(after stem cell transplantation or intensive chemotherapy).

Study Overview

• Status: Recruiting
• Conditions: Multiple Myeloma
• Intervention / Treatment: Biological: CART-138/BCMA/19/more

Detailed Description

Adults ages 18-75 with Relapsed and/or Chemotherapy Refractory Multiple Myelomas.

Design:

Participants may be screened with:

Medical history Physical exam Blood and urine tests Heart tests Bone marrow sample Multiple scans and X-rays Lymphocytes are collected by apheresis from the enrolled patient or a healthy donor. Blood is removed through a needle in an arm. The rest of the blood is returned through a needle in the other arm.

The cells will be changed in a laboratory. Participants will get 2 chemotherapy drugs over 5 days. Two days later, participants will get an intravenous (IV) catheter in an arm. They will get the split doses CART cells on day0, day1, day2 through the IV in 1 infusion.

After this, participants will stay in the hospital for at least 9 days and stay nearby for 2 weeks. Then they will have blood tests and see a doctor.

Participants will visit the clinic at 1, 2, 3, 6, 9 and 12 months after the infusion, then every 6 months until two years after infusion. A bone marrow sample will be taken at the 3-month visit.

• Study Type: Interventional
• Enrollment (Anticipated): 10
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Ling zhi Yan, Phd; Phone Number: 13584821140; Email: yanlingzhi@suda.edu.cn

Study Locations

• China
  • Jiangsu
    • Suzhou, Jiangsu, China, 215000
      • Recruiting
      • First Affiliated Hospital, Soochow University
      • Contact: Ling zhi Yan, Phd; Phone Number: 13584821140; Email: yanlingzhi@suda.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• CD138 or BCMA antigen positive multiple myeloma in patients with no available curative treatment options (such as autologous or allogeneic SCT).
• Relapsed and/or refractory multiple myeloma.
• Relapsed after prior autologous or allogenic SCT.
• Expected survival ≥ 3 months
• Creatinine < 2.0 mg/dl
• Blood coagulation function: PT and APTT < 2x normal
• Arterial blood oxygen saturation > 92%
• Alanine Aminotransferase (ALT)/Aspartate Aminotransferase (AST) < 3x normal
• Karnofsky scores ≥ 60 and ECOG score ≤ 2
• Adequate venous access for apheresis, and no other contraindications for leukapheresis
• Patients should not take system chemotherapy in one month and immunotherapy in three months prior to CART cells infusion.
• Voluntary informed consent is given

Exclusion Criteria:

• Pregnant or lactating women
• Uncontrolled active infection.
• Active hepatitis B or hepatitis C infection.
• Concurrent use of systemic steroids. Recent or current use of inhaled steroids is not exclusionary.
• Previously treatment with any gene therapy products
• Any uncontrolled active medical disorder that would preclude participation as outlined.
• HIV infection.
• History of myocardial infarction and severe arrhythmia in half a year
• Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease).
• Patients with fever of unknown origin (T > 38℃)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: CART-138/BCMA/19/more	Biological: CART-138/BCMA/19/more; Cyclophosphamide，Fludarabine，CART-138/BCMA /19/more cells Cyclophosphamide: 300 mg/m2 IV over 30 minutes on days -5 , -4,and -3; Fludarabine: 30 mg/m2 IV over 30 minutes immediately following the cyclophosphamide on day -5, -4, and -3 Biological: Anti-CD138/BCMA/CD19/more total CART cells 5x106- 100x106 CAR+ T cells per kg of recipient bodyweight

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determine if there is grade 3 to 5 cytokine release syndrome	Number of Patients With Grade 3 Through Grade 5 Cytokine Release Syndrome(CRS) That Are Related to Study Intervening Measures, Graded According to NCI CTCAE Version 4.0	2 weeks-12 months after initial dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Investigators try to assess major reaction rate (MRR, PR+VGPR+CR) at the end of the research.	Number of Patients achieved major reaction rate (MRR;PR+VGPR+CR) According to IMWG response criteria at the end of the research.	up to 24 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Investigators try to test CART 138 cells copies in vivo.	CART Cell survival time by testing CART-138/BCMA cells copies in vivo through PCR Method.	2 years

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital of Soochow University

Publications and helpful links

General Publications

• Zhang Y, Zhang C, Zhou J, Zhang J, Chen X, Chen J, Wang P, Sun X, Lou X, Qi W, Kang L, Yu L, Wu D, Li C. Case Report: Reversible Neurotoxicity and a Clinical Response Induced by BCMA-Directed Chimeric Antigen Receptor T Cells Against Multiple Myeloma With Central Nervous System Involvement. Front Immunol. 2021 Feb 25;12:552429. doi: 10.3389/fimmu.2021.552429. eCollection 2021.

Study record dates

Study Major Dates

• Study Start: September 1, 2016
• Primary Completion (ANTICIPATED): September 1, 2026
• Study Completion (ANTICIPATED): December 1, 2026

Study Registration Dates

• First Submitted: October 19, 2016
• First Submitted That Met QC Criteria: June 21, 2017
• First Posted (ACTUAL): June 22, 2017

Study Record Updates

• Last Update Posted (ACTUAL): May 2, 2019
• Last Update Submitted That Met QC Criteria: April 30, 2019
• Last Verified: September 1, 2016

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
• Other Study ID Numbers: myeloma-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO