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Multiple MyelomaPhase 1/2APRILNCT03287804

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

A Phase 1/2 study testing AUTO2 in people with Multiple Myeloma, run by Autolus Limited at 4 sites in 2 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Multiple Myeloma
What is being tested?
AUTO2
Could I receive a placebo?
No, everyone receives an active treatment
How many people
12 participants
Where
4 sitesin 2 countries
Study dates
5 May 2017to 5 Sep 2019
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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).
Show all 11Show fewer
  • 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.

Trial locations and contacts

4 sites in 2 countries.

4 sites in 2 countries

United Kingdom3 sites

  • University College London Hospitals NHS Foundation Trust

    London

  • The Christie NHS Foundation Trust

    Manchester, M20 4BX

  • Freeman Hospital, The Newcastle upon Tyne Hospitals NHS Foundation Trust

    Newcastle upon Tyne

Other trials in United Kingdom

Netherlands1 site

  • VU University Medical Centre Amsterdam

    Amsterdam

Other trials in Netherlands

About this study

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

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.

Read the 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.

Being tested
AUTO2
Keywords
Multiple Myeloma, Relapsed Multiple Myeloma, Refractory Multiple Myeloma, AUTO2
Medical subject headings
Multiple Myeloma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AUTO2Biological

    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

Study groups in NCT03287804
Study groupRoleWhat they receive
AUTO2ExperimentalRelapsed or refractory Myeloma patients
Receives: Biological: AUTO2

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    Measured: Up to 28 days post-infusion

  2. 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.

    Measured: Up to 28 days post-infusion

  3. 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

    Measured: Up to 2 years

Secondary outcomes (7)

  1. Proportion of Patients for Whom an AUTO2 Product Can be Generated

    Feasibility of product generation was examined by assessing the number of AUTO2 successfully manufactured as a fraction of the number of patients undergoing leukapheresis (all patients registered).

    Measured: Up to 2 years

  2. Clinical Benefit Rate

    Number of subjects exhibiting stringent complete response, complete response, very good partial response, partial response or minor response following treatment with AUTO2

    Measured: Up to 2 years

  3. Duration of Response

    Calculated from the date of first observation of sCR, CR, VGPR or PR to the date of disease progression, relapse or death, for patients who were considered responders (achieved at least PR). Patients who had not progressed, relapsed or died will be censored at the last adequate disease assessment.

    Measured: Up to 2 years

  4. Time to Disease Progression

    Calculated from the date of AUTO2 treatment to the date of progression. Patients who had not progressed, relapsed or died without progression/relapse will be censored at the last adequate disease assessment.

    Measured: Up to 2 years

  5. Progression-free Survival

    Calculated from the date of AUTO2 treatment to the date of progression or death. Patients who have not progressed or relapsed was censored at the last adequate disease assessment

    Measured: Up to 2 years

  6. Overall Survival

    Descriptive analysis based on number of patients alive at database lock (1-May-2020).

    Measured: Up to 2 years

  7. Number of Patients With Expansion Followed by Persistence of RQR8/APRIL CAR Positive T Cells in the Peripheral Blood

    Expansion and persistence of RQR8/APRIL CAR positive T cells as determined by quantitative polymerase chain reaction and/or flow cytometry.

    Measured: Up to 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Sep 2017
  2. Study start5 May 2017
  3. Primary completion5 Sep 2019
  4. Study completion5 Sep 2019

Why it stopped: Preliminary efficacy seen to date following treatment with AUTO2 has been determined not sufficient to warrant further development

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
12 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03287804
Sponsor's protocol ID
AUTO2-MM1
Other IDs
2016-003893-42, 2016
Acronym
APRIL
Status last verified
Sep 2020
First submitted
11 Sep 2017
Last updated
23 Oct 2020
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • 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.

    PubMed 37399355

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing AUTO2 in people with Multiple Myeloma, run by Autolus Limited at 4 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 23 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in United Kingdom, Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 23 Oct 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Phase I - Number of Subjects With Grade 3 to 5 Toxicity During the Dose Limiting Toxicity (DLT) Period (time frame: Up to 28 days post-infusion). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03287804, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Oct 2020.

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