Study to Evaluate the Safety and Efficacy of Anti-CD38 CAR-T in Relapsed or Refractory Multiple Myeloma Patients

NCT03464916 | Completed Phase 1 FDA Drug

• 1 other identifier: SOR-CART-MM-001
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 4

Brief Summary

The study is an open-label Phase 1 single dose-escalation safety study of CAR2 Anti-CD38 A2 CAR-T Cells in patients with Relapsed or Refractory Multiple Myeloma, who meet all other eligibility criteria.

Conditions

Relapsed or Refractory Multiple Myeloma

Keywords

CAR2 Anti-CD38 A2 CAR-T Cells

Outcome Measures

Primary Outcomes (1)

• Determine the MTD

  The MTD is assessed according to a 3+3 dose-escalation design by the occurrence of treatment-emergent dose-limiting toxicities during the 28-day Treatment Period in the dose-escalation phase of the study

  28 days

Secondary Outcomes (14)

• Determine the CAR2 Anti-CD38 A2 CAR-T cell blood concentrations (Pharmacokinetic [PK] Profile) to evaluate the Cmax

  28 days

• Determine the CAR2 Anti-CD38 A2 CAR-T cell blood concentrations (Pharmacokinetic [PK] Profile) to evaluate the AUC

  28 days

• Evaluate the safety of Anti-CD38 A2 CAR-T cells in Patients with RRMM by incidence of treatment-emergent adverse events

  6 months

• Assess preliminary efficacy by response rate in accordance with the modified International Myeloma Working Group (IMWG) criteria

  6 months

• Assess preliminary efficacy by depth of response in accordance with the modified International Myeloma Working Group (IMWG) criteria.

  6 months

Other Outcomes (6)

• An assessment of pharmacodynamics will be based on determining if there is an association of the achievement of at least a partial response with the level of Cmax of circulating CAR-T cells.

  6 months

• An assessment of pharmacodynamics will be based on determining if there is an association of the achievement of at least a partial response with the AUC of circulating CAR-T cells.

  6 months

• An assessment of pharmacodynamics will be based on determining if there is an association of the incidence of at least Grade 3 cytokine release syndrome (CRS) adverse events with the level of Cmax of circulating CAR-T cells.

  6 months

Study Arms (1)

CAR2 Anti-CD38 A2 CAR-T Cells

EXPERIMENTAL

Relapsed or Refractory Multiple Myeloma

Biological: CAR2 Anti-CD38 A2 CAR-T Cells

Interventions

CAR2 Anti-CD38 A2 CAR-T Cells BIOLOGICAL

Autologous IV infusion; dose-escalation

CAR2 Anti-CD38 A2 CAR-T Cells

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The patient must either have relapsed refractory multiple myeloma (RRMM) after receiving prior lines of anti-myeloma treatments that included at least lenalidomide (Revlimid®), pomalidomide (Pomalyst®), bortezomib (Velcade®), carfilzomib (Kyprolis®), and daratumumab (Darzalex®) (refractory MM is defined as the development of disease progression during therapy with an anti-myeloma regimen or within 60 days of the last dose of an anti-myeloma regimen or the achievement of less than a partial response (PR) after greater than or equal to 2 cycles; for relapsing patients the duration from the last dose of the last prior treatment regimen to relapse must be less than or equal to 12 months); OR have multiple myeloma that is refractory to or has relapsed within 1 year of receiving high-dose therapy \[HDT\]/autologous stem cell transplantation \[ASCT\] in first- or second-line (refractory is defined as the achievement of less than a PR at the Day 90 to 100 post-ASCT response assessment)
• Must have measurable disease as defined by the following: Serum M-protein greater than or equal to 1 g/dL; OR Urine M-protein greater than or equal to 200 mg/24 hours; OR Serum free light chain (FLC) assay; involved FLC level greater than or equal to 10 mg/dL provided the serum FLC ratio is abnormal; OR greater than or equal to 30% clonal plasma cells in the bone marrow aspirate or biopsy sample
• Must have a life expectancy of at least 12 weeks
• Subjects should be willing and able to comply with the study schedule and protocols
• Females of childbearing potential must have 2 negative pregnancy tests, agree to ongoing pregnancy testing during the study, and sexually active female and male subjects must be willing to use an effective method to avoid pregnancies.

You may not qualify if:

• Subjects who received anticancer therapy or investigational drug within 28 days of first dose
• Subjects who received any approved anticancer chemotherapy within 21 days of first dose (exception cyclophosphamide as NMA conditioning)
• Subjects with unresolved toxicity greater than Grade 2 from previous therapies
• Have myeloma involvement of central nervous system (CNS) or a history of brain metastasis or spinal cord compression
• Subjects with an ECOG performance status greater than or equal to 3
• Has received allogenic hematopoietic stem cell transplantation (HSCT) within 6 months, have active graft-versus-host disease (GVHD) following transplant, or receiving immunosuppressive therapy following a transplant
• Has received any CAR cell line therapies
• Has any clinically significant low baseline lab results for hemoglobin, platelet counts, and neutrophil counts, at screening unless resulting from underlying RRMM.
• Has any clinically significant elevated baseline lab results for serum creatinine, AST, and total bilirubin (except for patients in whom hyperbilirubinemia is attributed to Gilbert's syndrome) at screening regardless of causality.
• Known HIV or acquired immunodeficiency syndrome-related illness, acute or history of chronic hepatitis B or C.
• Female subjects who are pregnant or breastfeeding
• Active bacterial, viral or fungal infections
• Has active plasma cell leukemia
• Has medical condition, abnormality, or psychiatric illness that would prevent study participation
• Left ventricular ejection fraction (LVEF) less than 40%

Sponsors & Collaborators

• Sorrento Therapeutics, Inc.: lead

Study Sites (4)

Mayo Clinic Florida

Jacksonville, Florida, 32224, United States

Location

Mayo Clinic Minnesota

Rochester, Minnesota, 55905, United States

Location

Icahn School of Medicine

New York, New York, 10029, United States

Location

University of Pennsylvania, Abramson Cancer Center

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Conditions

Recurrence; Multiple Myeloma

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Edward Stadtmauer, MD

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: To determine DLT and MTD, the design uses a 3+3 rule-based design. Dose escalation is permitted between successive cohorts based upon a specified algorithm, using discrete dosage steps.

Study Record Dates

• First Submitted: February 14, 2018
• First Posted: March 14, 2018
• Study Start: October 15, 2018
• Primary Completion: August 23, 2020
• Study Completion: February 28, 2022
• Last Updated: March 16, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)