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

NCT03287804 | Terminated Phase 1 Results DMC FDA Drug

• 2 other identifiers: AUTO2-MM12016-003893-42
• Study Type: interventional
• Target: 12
• Locations: 2 countries
• Sites: 4

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.

Conditions

Multiple Myeloma

Keywords

Multiple Myeloma; Relapsed Multiple Myeloma; Refractory Multiple Myeloma; AUTO2

Outcome Measures

Primary Outcomes (3)

• Phase I - Number of Subjects With Grade 3 to 5 Toxicity During the Dose Limiting Toxicity (DLT) Period

  Up to 28 days post-infusion

• Phase I - Number of Subjects With a Dose Limiting Toxicity (DLT)

  Dose limiting toxicity was defined as: Any new non-hematological AE of Grade 3 or higher toxicity using the NCI CTCAE (Version 4.03), which is probably or definitely related to AUTO2 therapy, which occurs within the DLT evaluation period, and which fails to resolve to Grade 2 or better within 14 days, despite appropriate supportive measures; A Grade 4 CRS; Any other reason for activation of the safety switch after receiving AUTO2; Any other fatal event (Grade 5) or life-threatening event (Grade 4) that cannot be managed with conventional supportive measures or which in the opinion of the SEC necessitates dose reduction or other modification to trial treatment to avoid a similar hazard in future patients. Effort should be made to perform an autopsy in case of fatal event where the aetiology is unclear; Any event that in the opinion of treating investigators and/or Medical Monitor puts the patient at undue risk may also be considered a DLT.

  Up to 28 days post-infusion

• Number of Infused Patients With Best Overall Response

  Best overall response was defined as stringent complete response + complete response + very good partial response + partial response following treatment with AUTO2. Response Criteria Per IMWG Consensus Recommendations

  Up to 2 years

Secondary Outcomes (7)

• Proportion of Patients for Whom an AUTO2 Product Can be Generated

  Up to 2 years

• Clinical Benefit Rate

  Up to 2 years

• Duration of Response

  Up to 2 years

• Time to Disease Progression

  Up to 2 years

• Progression-free Survival

  Up to 2 years

Study Arms (1)

AUTO2

EXPERIMENTAL

Relapsed or refractory Myeloma patients

Biological: AUTO2

Interventions

AUTO2 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

AUTO2

Eligibility Criteria

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

You may qualify if:

• Male or female patients, aged ≥ 18.
• Willing and able to give written, informed consent.
• Confirmed diagnosis of MM.
• Measurable disease as defined by IMWG.
• 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.
• For females of childbearing potential, a negative serum or urine pregnancy test must be documented at screening and confirmed before receiving study treatment.
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 1.
• Peripheral blood total lymphocyte count \> 0.5 x 10⁹/L.

You may not qualify if:

• Women who are pregnant or lactating.
• Prior treatment with investigational or approved gene therapy or cell therapy products.
• Patient has previously received an allogenic stem cell transplant.
• Clinically significant, uncontrolled heart disease or a recent (within 6 months) cardiac event.
• Left Ventricular Ejection fraction \< 50 unless the institutional lower limit of normal is lower.
• 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).
• Chronic renal impairment requiring dialysis, or calculated creatinine clearance \< 30 mL/min
• 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.
• Active autoimmune disease requiring immunosuppression.
• 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.
• Known allergy to albumin, dimethyl sulfoxide (DMSO), cyclophosphamide or fludarabine.

Sponsors & Collaborators

• Autolus Limited: lead

Study Sites (4)

VU University Medical Centre Amsterdam

Amsterdam, Netherlands

Location

University College London Hospitals NHS Foundation Trust

London, United Kingdom

Location

The Christie NHS Foundation Trust

Manchester, M20 4BX, United Kingdom

Location

Freeman Hospital, The Newcastle upon Tyne Hospitals NHS Foundation Trust

Newcastle upon Tyne, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 37399355 DERIVED

MeSH Terms

Conditions

Multiple Myeloma

Condition Hierarchy (Ancestors)

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

Limitations and Caveats

Early termination leading to small numbers of patients analyzed

Results Point of Contact

• Title: Clinical Project Manager
• Organization: Autolus Ltd

clinicaltrials@autolus.com

+44 1483 920748

Study Officials

• Autolus Limited

  Sponsor GmbH

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: September 11, 2017
• First Posted: September 19, 2017
• Study Start: May 5, 2017
• Primary Completion: September 5, 2019
• Study Completion: September 5, 2019
• Last Updated: October 23, 2020
• Results First Posted: October 23, 2020

Record last verified: 2020-09

Locations

GB (3); NL (1)