APRIL CAR T Cells (AUTO2) Targeting BCMA and TACI for the Treatment of Multiple Myeloma

NCT ID: NCT03287804

Last Updated: 2020-10-23

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-05-05
• Study Completion Date: 2019-09-05

Brief Summary

The purpose of this study is to test the safety and efficacy of AUTO2, a CAR T Cell Treatment Targeting BCMA and TACI, in Patients with Relapsed or Refractory Multiple Myeloma.

Detailed Description

The study will consist of 2 phases, a Phase I/dose escalation phase and a Phase II/expansion phase. Patients with relapsed and relapsed or refractory multiple myeloma will be enrolled in both phases of the study. Eligible patients will undergo leukapheresis in order to harvest T cells, which is the starting material for the manufacture of the autologous CAR T product AUTO2. AUTO2 has a dual target BCMA (B cell maturation antigen) and TACI (Transmembrane activator and calcium modulator and cyclophilin ligand interactor). Following pre-conditioning by a chemotherapeutic regimen, the patient will receive AUTO2 intravenously as a single or split dose and will then enter a 12-month follow-up period.

Conditions

Multiple Myeloma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

AUTO2

Relapsed or refractory Myeloma patients

Group Type: EXPERIMENTAL

AUTO2

Intervention Type: BIOLOGICAL

AUTO2 (APRIL CAR T Cells) Following preconditioning with chemotherapy (cyclophosphamide and fludarabine) patients will be treated with doses from 15 x 10⁶ to 350 x 10⁶ APRIL CAR T Cells.

Following Phase 2 dose determination patients will be treated with selected dose of APRIL CAR T Cells

Interventions

AUTO2

AUTO2 (APRIL CAR T Cells) Following preconditioning with chemotherapy (cyclophosphamide and fludarabine) patients will be treated with doses from 15 x 10⁶ to 350 x 10⁶ APRIL CAR T Cells.

Following Phase 2 dose determination patients will be treated with selected dose of APRIL CAR T Cells

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

1. Male or female patients, aged ≥ 18.

2. Willing and able to give written, informed consent.

3. Confirmed diagnosis of MM.

4. Measurable disease as defined by IMWG.

5. Relapse or refractory disease and have had at least 3 different prior lines of therapy including proteasome inhibitor, alkylator and immunomodulatory therapy (IMiD), or have "double refractory" disease to a proteasome inhibitor and IMiD.

6. For females of childbearing potential, a negative serum or urine pregnancy test must be documented at screening and confirmed before receiving study treatment.

7. Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 1.

8. Peripheral blood total lymphocyte count > 0.5 x 10⁹/L.

Exclusion Criteria

1. Women who are pregnant or lactating.

2. Prior treatment with investigational or approved gene therapy or cell therapy products.

3. Patient has previously received an allogenic stem cell transplant.

4. Clinically significant, uncontrolled heart disease or a recent (within 6 months) cardiac event.

5. Left Ventricular Ejection fraction < 50 unless the institutional lower limit of normal is lower.

6. Significant liver disease: alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 3 × ULN, or total bilirubin > 2.0 mg/dL or evidence of end stage liver disease (e.g. ascites, hepatic encephalopathy).

7. Chronic renal impairment requiring dialysis, or calculated creatinine clearance < 30 mL/min

8. Active infectious bacterial or viral disease (hepatitis B virus, hepatitis C virus, human immunodeficiency virus, human T-lymphotropic virus or syphilis) requiring treatmenUse of rituximab within the last 3 months.

9. Active autoimmune disease requiring immunosuppression.

10. Received any anti-myeloma therapy within the last 21 days prior to preconditioning or 10 days prior to leukapheresis; steroids of up to 160 mg of dexamethasone are permitted so long as > 7 days post-dose prior to pre-conditioning or leukapheresis.

11. Known allergy to albumin, dimethyl sulfoxide (DMSO), cyclophosphamide or fludarabine.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Autolus Limited

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Autolus Limited

Role: STUDY_DIRECTOR

Sponsor GmbH

Locations

VU University Medical Centre Amsterdam

Amsterdam, , Netherlands

University College London Hospitals NHS Foundation Trust

London, , United Kingdom

The Christie NHS Foundation Trust

Manchester, , United Kingdom

Freeman Hospital, The Newcastle upon Tyne Hospitals NHS Foundation Trust

Newcastle upon Tyne, , United Kingdom

Countries

Netherlands; United Kingdom

References

Lee L, Lim WC, Galas-Filipowicz D, Fung K, Taylor J, Patel D, Akbar Z, Alvarez Mediavilla E, Wawrzyniecka P, Shome D, Reijmers RM, Gregg T, Wood L, Day W, Cerec V, Ferrari M, Thomas S, Cordoba S, Onuoha S, Khokhar N, Peddareddigari V, Al-Hajj M, Cavet J, Zweegman S, Rodriguez-Justo M, Youg K, Pule M, Popat R. Limited efficacy of APRIL CAR in patients with multiple myeloma indicate challenges in the use of natural ligands for CAR T-cell therapy. J Immunother Cancer. 2023 Jun;11(6):e006699. doi: 10.1136/jitc-2023-006699.

Reference Type: DERIVED

PMID: 37399355 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2016-003893-42

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

AUTO2-MM1

Identifier Type: -

Identifier Source: org_study_id