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

Safety and Efficacy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03455972
• Other study ID #: myeloma-03
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: February 20, 2018
• Est. completion date: December 2023

Study information

• Verified date: December 2020
• Source: The First Affiliated Hospital of Soochow University
• Contact: chengcheng fu
• Phone: 0086-0512-67781856
• Email: fuzhengzheng[@]suda.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 15
• Est. completion date: December 2023
• Est. primary completion date: December 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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?).

Related Conditions & MeSH terms

• Multiple Myeloma
• Safety and Efficacy

Intervention

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

Locations

Country	Name	City	State
China	First Affiliated Hospital, Soochow University	Suzhou	Jiangsu

Sponsors (1)

Lead Sponsor	Collaborator
The First Affiliated Hospital of Soochow University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence and severity of adverse events	Proportion of subjects with adverse events overall and by severity grade	Approximately 3 years
Primary	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
Primary	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	Duration of best response	According to IMWG response criteria at the end of the research.	Minimum of 2 years
Secondary	MRD negative conversion ratio and persistence	MRD negative by flow cytometry	Minimum of 2 years
Secondary	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
Secondary	Pharmacokinetics - Cmax	Maximum transgene level	Approximately 2.5 years after first CAR infused
Secondary	Pharmacokinetics - Tmax	Time to peak transgene level	Approximately 2.5 years after first CAR infused
Secondary	Pharmacokinetics - AUC	Area under the curve of the transgene level	Approximately 2.5 years after first CAR infused
Secondary	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