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B-cell LymphomaPhase 1/2CARMA-01NCT06002659

CAR20(NAP)-T Therapy for B Cell Lymphoma (CARMA-01 Study)

A Phase 1/2 study testing CAR20(NAP)-T, Cyclophosphamide and Fludarabine in people with B-cell Lymphoma, run by Uppsala University at 2 sites in Sweden.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

The purpose is to study the safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy of CAR20(NAP)-T for patients with B-cell malignancies. Read more about this study

Who is it for?
Any age
Conditions the study is for
B-cell Lymphoma
What is being tested?
CAR20(NAP)-T, Cyclophosphamide and Fludarabine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
18 participants
Where
2 sitesSweden
Study dates
1 May 2024to 30 Dec 2027
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

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 Any age
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Signed informed consent.
  • Relapsed or refractory CD20+ diffuse large B-cell lymphoma, mantle cell lymphoma or indolent lymphoma.
  • The patient should have been treated with at least two lines of therapy and have no curative treatment option, specifically
  • Relapsed or refractory CD20+ B-cell lymphoma that are not eligible to receive clinically approved CD19-directed CAR T cell treatment.
  • Relapsed or refractory CD20+ B-cell lymphoma who are CD19 negative.
  • Relapsed or refractory B-cell lymphoma who relapse after CD19 CAR T cell treatment.
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  • In phase I age >18 years, in phase II all ages
  • Measurable disease per Lugano classification.
  • Performance status ECOG 0-2.
  • Adequate bone marrow function as evidenced by:
  • Absolute neutrophil count (ANC) ≥ 1x10^9/l/L
  • Platelet ≥ 50x 10^9/l
  • Absolute lymphocyte count ≥ 0,1x10^9/L
  • Adequate renal, hepatic, cardiac, and pulmonary function as evidenced by:
  • Creatinine clearance (Cockcroft Gault) ≥ 30 mL/min
  • Serum Alanine aminotransferase/Aspartate aminotransferase (ALT/AST) ≤ 2.5 Upper limit of normal (ULN) and S-Bilirubin <1.5x UNL
  • Cardiac ejection fraction ≥ 40%
  • Functional venous for administration of IMP.
  • Fertile individuals must consent to use contraceptives during participation in the trial.

Who cannot join

  • Other CD20-positive lymphomas i.e Burkitt lymphoma, primary CNS lymphoma, plasmablastic lymphoma or CLL transformed to DLBCL/HGBL (Richter transformation)
  • Any significant medical or psychiatric illness that would prevent the subject from giving informed consent or from following the study procedures.
  • Known human immunodeficiency virus (HIV) infection.
  • Impending organ-compromising disease.
  • Rapidly progressing disease
  • Active and/or severe infection (e.g., tuberculosis, sepsis and opportunistic infections, active hepatitis B virus (HBV) or active hepatitis C virus (HCV) infection.
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  • Other serious underlying medical conditions, which, in the Investigator's judgment, could impair the ability of the subject to perform the treatment.
  • Treatment with an investigational product within 30 days prior to enrolment
  • Potential sign of hypersensitivity reaction to tocilizumab or any of the agents used in this study
  • Systemic corticosteroid treatment (>10mg/day) <5 days prior to IMP treatment or <7 days prior leukapheresis.
  • Pregnancy

Trial locations and contacts

2 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Gunilla Enblad, MD/PhD contact

+46186110000

gunilla.enblad@igp.uu.se

Di Yu, PhD contact

+46707204196

di.yu@igp.uu.se

Sweden2 sites, 1 recruiting

  • Karolinska University Hospital

    Stockholm

    Active, not recruiting

  • Uppsala University Hospital

    Uppsala

    Gunilla Enblad

    Gunilla Enblad, MD/PhD

    Recruiting

Other trials in Sweden

About this study

Official title: A Phase I/IIa Multicenter Study Evaluating the Safety and Efficacy of CAR20(NAP)-T in Patients With Relapsed/Refractory B Cell Lymphoma (CARMA-01 Study)

The purpose is to study the safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy of CAR20(NAP)-T for patients with B-cell malignancies.

Read the detailed description

A cancer patient's T cells can be isolated and engineered to express a chimeric antigen receptor (CAR), which re-directs the T cells to recognize and kill tumor cells expressing that particular antigen. CD19-targeted CAR-T cell therapy has shown good effects for B cell malignancies, even cure, in otherwise therapy refractory patients.

Antigen escape, i.e., the downregulation of the antigen targeted by the CAR due to the selective pressure caused by the CAR-T cell therapy is a challenge. For patients treated with CD19 CAR-T cell therapy, about 30% of the patients are resistant to treatment and about 20% of patients relapse after an initial response.

CAR20(NAP)-T cells target CD20 and upon target recognition secrete a bacterial-derived pluripotent immune-stimulating factor named NAP (Helicobacter pylori Neutrophil-activating protein). Secretion of NAP in the tumor microenvironment can induce an endogenous bystander immune response, that counteracts antigen escape and thereby improves the therapeutic outcome.

CAR20(NAP)-T is an investigational agent not yet approved by authorities.

Design:

The study is designed as 3+3 dose escalation phase I, and a dose expansion Phase IIa. The safety, tolerability, PK/PD, and efficacy will be evaluated.Dose escalation is to be based on the incidence of dose-limiting toxicity (DLTs). The investigator or sub-investigator will decide if the AE is related to IMP-treatment on a case-by-case basis depending on the character of the DLT symptoms. Investigator or sub-investigator has a possibility to classify various toxicity observed in patient as DLT.The Recommended phase II dose (RP2D) is decided based on safety, PK/PD data as well as preliminary clinical activity data from the Phase I dose escalation. After setting the RP2D, additional patients will be treated at RP2D to make sure at least 6 patients will be treated at RP2D dose level already at the phase I part.

Protocol treatment:

The enrolled patient will undergo a leukapheresis procedure to harvest enough T cells for IMP production. During CAR20(NAP)-T manufacturing, the patient may receive bridging therapy to control tumor burden. All patients will receive pre-conditioning chemotherapy (cyclophosphamide and fludarabine) followed by one dose of CAR20(NAP)-T cell infusion intravenously. The patient will then be followed by doctor/study nurse for evaluation of the health status and side effects. At follow-up visits, blood samples will be obtained and CT imaging will be performed. Patient will actively participate in the study for about 24 months when the final follow-up visit will be scheduled.

Conditions
B-cell Lymphoma
Being tested
CAR20(NAP)-T, Cyclophosphamide, Fludarabine
Keywords
CAR T cell, B cell lymphoma, CD20, HP-NAP
Medical subject headings
Lymphoma, B-Cell

What participants receive

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

  • CAR20(NAP)-TBiological

    Also called ELC-301

    Autologous CAR-T cells targeting CD20 and upon target recognition express and secrete NAP

  • CyclophosphamideDrug

    pre-conditioning chemotherapy

  • FludarabineDrug

    pre-conditioning chemotherapy

Study groups in NCT06002659
Study groupRoleWhat they receive
TreatmentExperimentalCAR20(NAP)-T treatment
Receives: Biological: CAR20(NAP)-T; Drug: Cyclophosphamide; Drug: Fludarabine

What is being measured

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

  1. Incidence of dose limiting toxicity

    The incidence of dose limiting toxicity (DLT). Number of Participants Experiencing Adverse Events (AEs) Defined as Dose Limiting Toxicities (DLTs)

    Measured: First infusion up to 30 days

  2. Adverse events

    The nature, frequency, severity, and tolerability of adverse events (AEs) including clinically significant laboratory data, and their relation to dosage.

    Measured: 24 months

  3. Pharmacodynamic (PD) and pharmacokinetic (PK)

    PD is assessed by determine circulating B cell level; PK is assessed by determine circulating CAR20(NAP)-T cells.

    Measured: Either 24 month or 15 years during long-term follow up if clinically indicated

Secondary outcomes (5)

  1. Objective response rate [ORR]

    ORR is defined as the incidence of a complete response or a partial response by the revised Lugano classification as determined by the study investigators. All patients that do not meet the criteria for an objective response by the analysis cutoff date will be considered non-responders.

    Measured: 24 months

  2. Progression free survival [PFS]

    PFS is defined as the time from the IMP treatment date to the date of disease progression per the revised Lugano classification or death from any cause.

    Measured: 24 months

  3. Best Objective Response

    the incidence of complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD), or unevaluable (UE) as best response to treatment.

    Measured: 24 months

  4. Duration of Response (DOR)

    DOR is defined as the date of their first objective response (which is subsequently confirmed) to disease progression per the revised Lugano classification or death regardless of cause. Patients not meeting the criteria for progression or death by the analysis data cutoff date will be censored at their last evaluable disease assessment date and their response will be noted as ongoing.

    Measured: 24 months

  5. Overall Survival (OS)

    defined as the time from IMP treatment to the date of death. Patients alive by the analysis data cutoff date will be censored at their last contact date. The overall survival rate will be reported at different cut-off time points.

    Measured: either 24 months or 15 years during long-term follow up if clinically indicated

Timeline

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

  1. First posted21 Aug 2023
  2. Study start1 May 2024
  3. Primary completion30 Dec 2027 (estimated)
  4. Study completion30 Dec 2027 (estimated)

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
18 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06002659
Sponsor's protocol ID
ELC301-CARMA-01
Other IDs
2022-004157-31
Acronym
CARMA-01
Status last verified
May 2024
First submitted
6 Jan 2023
Last updated
9 May 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Jin C, Ma J, Ramachandran M, Yu D, Essand M. CAR T cells expressing a bacterial virulence factor trigger potent bystander antitumour responses in solid cancers. Nat Biomed Eng. 2022 Jul;6(7):830-841. doi: 10.1038/s41551-022-00875-5. Epub 2022 Apr 4.

    PubMed 35379957

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing CAR20(NAP)-T, Cyclophosphamide and Fludarabine in people with B-cell Lymphoma, run by Uppsala University at 2 sites in Sweden.

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 19 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: looking for participants now, as of the sponsor's last update on 9 May 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Sweden. 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?

This study is still under way. Results are not available in the source record yet.

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

Contact Gunilla Enblad, MD/PhD (+46186110000, gunilla.enblad@igp.uu.se), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of dose limiting toxicity (time frame: First infusion up to 30 days). 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 NCT06002659, 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 9 May 2024.

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