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

This study is currently recruiting participants.
Verified September 2017 by Autolus Limited
Sponsor:
ClinicalTrials.gov Identifier:
NCT03287804
First Posted: September 19, 2017
Last Update Posted: November 2, 2017
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.
Information provided by (Responsible Party):
Autolus Limited
  Purpose
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 Intervention Phase
Multiple Myeloma Biological: AUTO2 Phase 1 Phase 2

Study Type: Interventional
Study Design: 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

Resource links provided by NLM:


Further study details as provided by Autolus Limited:

Primary Outcome Measures:
  • 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 ]
  • Phase II - Anti-myeloma response as per International Myeloma Working Group (IMWG) consensus recommendations [ Time Frame: 12 months post-treatment ]

Secondary Outcome Measures:
  • 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 ]
  • 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 ]

Estimated Enrollment: 80
Actual Study Start Date: May 5, 2017
Estimated Study Completion Date: October 2020
Estimated Primary Completion Date: October 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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


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.
  Eligibility

Information from the National Library of Medicine

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

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.
  Contacts and Locations
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 ClinicalTrials.gov identifier (NCT number): NCT03287804


Contacts
Contact: Autolus Limited +44 (0)2038296230 contact@autolus.com

Locations
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 Not yet recruiting
Newcastle upon Tyne, United Kingdom
Principal Investigator: Dr Tobias Menne         
Sponsors and Collaborators
Autolus Limited
Investigators
Study Director: Autolus Limited Sponsor GmbH
  More Information

Responsible Party: Autolus Limited
ClinicalTrials.gov Identifier: NCT03287804     History of Changes
Other Study ID Numbers: AUTO2-MM1
2016-003893-42 ( EudraCT Number )
First Submitted: September 11, 2017
First Posted: September 19, 2017
Last Update Posted: November 2, 2017
Last Verified: September 2017

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
AUTO2

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