Clinical trial NCT03455972: Study of T Cells Targeting CD19/BCMA (CART-19/BCMA) for High Risk Multiple Myeloma Followed With Auto-HSCT
Official title: Study of T Cells Targeting CD19/BCMA (CART-19/BCMA) for High Risk Multiple Myeloma Followed With Auto-HSCT
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Safety and Efficacy
Lead sponsor: The First Affiliated Hospital of Soochow University
Sponsor class: OTHER
First posted: 2018-03-07
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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℃).

Primary outcomes:
measure: Incidence and severity of adverse events
timeFrame: Approximately 3 years
measure: PFS
timeFrame: Minimum of 2 years after first induction
measure: OS
timeFrame: Minimum of 2 years after first induction
Secondary outcomes:
measure: Duration of best response
timeFrame: Minimum of 2 years
measure: MRD negative conversion ratio and persistence
timeFrame: Minimum of 2 years
measure: Proportion of subjects who achieved Complete Response (CR) Rate
timeFrame: Minimum of 2 years
measure: Pharmacokinetics - Cmax
timeFrame: Approximately 2.5 years after first CAR infused
measure: Pharmacokinetics - Tmax
timeFrame: Approximately 2.5 years after first CAR infused
measure: Pharmacokinetics - AUC
timeFrame: Approximately 2.5 years after first CAR infused
measure: Duration of persistence of CAR T cells in the blood
timeFrame: Approximately 2.5 years after first CAR infused
Other outcomes:
Locations:
city: Suzhou
country: China
facility: First Affiliated Hospital, Soochow University
state: Jiangsu
Study officials:
affiliation: The First Affiliated Hospital of Soochow University
name: depei wu
role: STUDY_CHAIR
References: