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

Phase 2Active Not RecruitingNCT03455972

The First Affiliated Hospital of Soochow University43 enrolled

Overview

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.

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 3-6 months until disease progression. A bone marrow sample will be taken at the 3-6 months visit.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Safety and Efficacy

Interventions

anti-CD19 and anti-BCMA CARBIOLOGICAL

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)

Immunomodulatory drugsDRUG

Maintenance therapy

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

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℃).

Locations (1)

First Affiliated Hospital, Soochow University

Suzhou, Jiangsu, China

Outcomes

Primary Outcomes

Incidence and severity of adverse events

Proportion of subjects with adverse events overall and by severity grade

Time frame: Approximately 2 years

PFS, response

mPFS of all patients. PFS is defined as time from first induction date to first documentation of PD, or death due to any cause, whichever occurs first. Percentage of patients with sCR. Response was graded according to IMWG response criteria.

Time frame: every 6 months after first induction

CAR-T Pharmacokinetics

Maximum transgene level, Time to peak transgene levelm, persistence

Time frame: Minimum of 2 years after first induction

Secondary Outcomes

MRD negative conversion ratio and persistence

MRD negativity by flow cytometry

Time frame: every 3 months for first year, then every 6 months

lymphocyte subsets analysis

Proportion of sub-lymphocytes Monitoring by flow cytometry

Time frame: Minimum of 2 years

immune mutation

Proportion of T-reg cells and B-reg cells detected whether the treatment process induces an immune response to murine single-chain antibodies in patients

Time frame: Minimum of 2 years

Patients quality of life

HRQoL was assessed with the EORTC QLQ-C30 after transplantation followed by CAR-T therapy.

Time frame: within 1 year post CART infusion

Data from ClinicalTrials.gov

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