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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03287804
Recruitment Status : Recruiting
First Posted : September 19, 2017
Last Update Posted : July 10, 2018
Information provided by (Responsible Party):
Autolus Limited

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.

Condition or disease Intervention/treatment Phase
Multiple Myeloma Biological: AUTO2 Phase 1 Phase 2

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.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Single-Arm, Open-Label, Multi-Centre, Phase I/II Study Evaluating the Safety and Clinical Activity of AUTO2, a CAR T Cell Treatment Targeting BCMA and TACI, in Patients With Relapsed or Refractory Multiple Myeloma
Actual Study Start Date : May 5, 2017
Estimated Primary Completion Date : October 2020
Estimated Study Completion Date : October 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma

Arm Intervention/treatment
Experimental: AUTO2
Relapsed or refractory Myeloma patients
Biological: 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

Primary Outcome Measures :
  1. Phase I - Safety (Frequency and severity of adverse events and serious AEs) and confirmation of phase II dose and schedule [ Time Frame: 1 year after treatment ]
  2. Phase II - Anti-myeloma response as per International Myeloma Working Group (IMWG) consensus recommendations [ Time Frame: 12 months post-treatment ]

Secondary Outcome Measures :
  1. Feasibility of generating AUTO2: Number of patients who cells achieve successful AUTO2 manufacture as a proportion of the number of patients undergoing leukapheresis [ Time Frame: Up to 8 weeks post leukapheresis ]
  2. clinical benefit (stringent complete response + complete response + very good partial response + partial response + minor response [sCR+CR+VGPR+PR+MR]) rate following AUTO2. Response criteria per IMWG consensus recommendations [ Time Frame: 12 months post AUTO2 treatment ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Key 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.

Key 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03287804

Contact: Autolus Limited +44 (0)1483 920748

VU University Medical Centre Amsterdam Recruiting
Amsterdam, Netherlands
Principal Investigator: Professor Sonja Zweegman         
United Kingdom
University College London Hospitals NHS Foundation Trust Recruiting
London, United Kingdom
Principal Investigator: Dr Rakesh Popat         
The Christie NHS Foundation Trust Recruiting
Manchester, United Kingdom, M20 4BX
Principal Investigator: Dr James Cavet         
Freeman Hospital, The Newcastle upon Tyne Hospitals NHS Foundation Trust Recruiting
Newcastle upon Tyne, United Kingdom
Principal Investigator: Dr Tobias Menne         
Sponsors and Collaborators
Autolus Limited
Study Director: Autolus Limited Sponsor GmbH

Responsible Party: Autolus Limited Identifier: NCT03287804     History of Changes
Other Study ID Numbers: AUTO2-MM1
2016-003893-42 ( EudraCT Number )
First Posted: September 19, 2017    Key Record Dates
Last Update Posted: July 10, 2018
Last Verified: July 2018

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Autolus Limited:
Multiple Myeloma
Relapsed Multiple Myeloma
Refractory Multiple Myeloma

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases