Study of T Cells Targeting CD19/BCMA (CART-19/BCMA) for High Risk Multiple Myeloma Followed With Auto-HSCT

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 high risk multiple myeloma after auto-HSCT.To test the safety and efficacy of giving targeting CD19 and BCMA T cells in treating high risk multiple myeloma followed with auto-HSCT.

Study Overview

• Status: Recruiting
• Conditions: Safety and Efficacy
• Intervention / Treatment: Biological: anti-CD19 and anti-BCMA CAR; Drug: Immunomodulatory drugs

Detailed Description

Adults ages 18-75 with high risk Multiple Myelomas (R-ISS III stage or with extramedullary infiltration or with del(17p), t(4;14), t(14;16), t(14;20), 1q21+ or disease progression during treatment).

Design:

Participants may be screened with:

Medical history Physical exam Blood and urine tests Heart tests Bone marrow sample Multiple scans and X-rays Participants will have apheresis. Blood is removed through a needle in an arm. T cells are removed. 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 auto-HSCT. Hematopoietic reconstitution after auto-HSCT, participants will get the T cells through the IV within 3 days. Maintenance therapy with IMiDs was received after combined CAR T 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 1, 2, 3, 6, 9 and 12 months after the infusion, then every 3 months until disease progression. A bone marrow sample will be taken at the 3-month visit.

• Study Type: Interventional
• Enrollment (Anticipated): 15
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: chengcheng fu; Phone Number: 0086-0512-67781856; Email: fuzhengzheng@suda.edu.cn

Study Locations

• China
  • Jiangsu
    • Suzhou, Jiangsu, China, 215000
      • Recruiting
      • First Affiliated Hospital, SooChow University
      • Contact: Shi xiaolan, Phd; Email: shixiaolan@suda.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Multiple myeloma patients eligible for auto-HSCT.
• High risk multiple myeloma (R-ISS III stage or with extramedullary infiltration or with del(17p), t(4;14), t(14;16), t(14;20), 1q21+ or disease progression during treatment).
• Expected survival ≥ 3 months.
• Creatinine < 2.0 mg/dl.
• Blood coagulation function: PT and APTT <2x normal.
• Arterial blood oxygen saturation>92%.
• ALT(alanine aminotransferase)/AST (aspartate aminotransferase)< 3x normal
• Karnofsky scores ≥ 60 and ECOG score≤2.
• Adequate venous access for apheresis, and no other contraindications for leukapheresis.
• Patients should not take 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: anti-CD19 and anti-BCMA CAR; Participants will get auto-HSCT. Hematopoietic reconstitution after auto-HSCT, participants will get the anti-CD19 CAR T cells (on d0) and anti-BCMA CAR T cells as split-dose (40% on d1 and 60% on d2)	Biological: anti-CD19 and anti-BCMA CAR; Participants will get auto-HSCT. Hematopoietic reconstitution after auto-HSCT, participants will get the anti-CD19 CAR T cells (1×10e+7/kg on d0) and anti-BCMA CAR T cells as split-dose (total 5×10e+7/kg, 40% on d1 and 60% on d2); Drug: Immunomodulatory drugs; Maintenance therapy; Other Names: IMiDs

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and severity of adverse events	Proportion of subjects with adverse events overall and by severity grade	Approximately 3 years
PFS	Is defined as time from first induction date to first documentation of PD, or death due to any cause, whichever occurs first.	Minimum of 2 years after first induction
OS	Is defined as time from first induction date to time of death due to any cause	Minimum of 2 years after first induction

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of best response	According to IMWG response criteria at the end of the research.	Minimum of 2 years
MRD negative conversion ratio and persistence	MRD negative by flow cytometry	Minimum of 2 years
Proportion of subjects who achieved Complete Response (CR) Rate	Percentage of subjects who achieved CR or stringent CR according to IMWG Uniform Response Criteria for Multiple Myeloma	Minimum of 2 years
Pharmacokinetics - Cmax	Maximum transgene level	Approximately 2.5 years after first CAR infused
Pharmacokinetics - Tmax	Time to peak transgene level	Approximately 2.5 years after first CAR infused
Pharmacokinetics - AUC	Area under the curve of the transgene level	Approximately 2.5 years after first CAR infused
Duration of persistence of CAR T cells in the blood	Duration of persistence of CAR T cells in the blood	Approximately 2.5 years after first CAR infused

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital of Soochow University

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 20, 2018
• Primary Completion (ANTICIPATED): December 1, 2021
• Study Completion (ANTICIPATED): December 1, 2023

Study Registration Dates

• First Submitted: February 19, 2018
• First Submitted That Met QC Criteria: March 5, 2018
• First Posted (ACTUAL): March 7, 2018

Study Record Updates

• Last Update Posted (ACTUAL): May 19, 2021
• Last Update Submitted That Met QC Criteria: May 17, 2021
• Last Verified: December 1, 2020

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; Neoplasms, Plasma Cell; Multiple Myeloma
• Other Study ID Numbers: myeloma-03

Drug and device information, study documents

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