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Mantle Cell Lymphoma (MCL)Phase 2FRONTIERNCT07569965

Frontline Risk-Adapted Optimization of Novel Targeted Immunotherapy Evaluation in High-Risk MCL

A Phase 2 study testing zamtocabtagene autoleucel (MB-CART2019.1), Cyclophosphamide and Fludarabine in people with Mantle Cell Lymphoma (MCL), run by Miltenyi Biomedicine GmbH.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Sites and contacts
Official record
Search all trials

Trial summary

FRONTIER is a prospective, single arm, open label, multi-center, Phase II study of MB-CART2019.1 (Zamtocabtagene Autoleucel) therapy as frontline consolidation for high-risk Mantle Cell Lymphoma (MCL) participants Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Mantle Cell Lymphoma (MCL)
What is being tested?
zamtocabtagene autoleucel (MB-CART2019.1), Cyclophosphamide and Fludarabine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
52 participants
Where
No sites listed yet
Study dates
Sep 2026to Mar 2030
Phase
Phase 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 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Diagnosis of MCL requires histologic confirmation by either overexpression of cyclin D1 OR presence of t(11;14) (q13; q32) translocation
  • Subject should have a tumor biopsy sample (at least 5 unstained slides of tissue or tissue block) available prior to MB-CART2019.1 infusion, preferably collected pre-induction.
  • If archival tissue is not available, the patient may be enrolled after discussion with the protocol chair and/or protocol officer
  • High Risk Disease at diagnosis, defined as having at least ONE of the criteria below:
  • High risk MIPI-c (as calculated by https://www.european-mcl.net/home/scores-mipi-mipi-c-19.html)
  • Simplified MIPI high-risk ≥6.2
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  • TP53 mutation OR ≥50% TP53 expression by IHC
  • Complex Karyotype [e.g. 3 or more cytogenetic abnormalities, excluding the presence or absence of t(11:14)]
  • Ki67≥ 50%
  • Blastoid or pleomorphic histology with Ki-67 ≥30%
  • Leptomeningeal Disease at diagnosis
  • NOTCH1 mutation
  • Received 2 cycles of appropriate systemic induction therapy, which includes a CD20 antibody +/- cytotoxic therapy +/- oral targeted therapy (e.g., BTKi, immunomodulatory imid drugs), with the following considerations:
  • CD20 antibody alone does not count towards a cycle of treatment
  • Induction cycles do not have to be identical
  • For BTKis and/or lenalidomide a cycle is defined as 14-28 days and will be based on institutional treatment regimens.
  • Intrathecal chemotherapy will not count towards a cycle of treatment
  • Radiation therapy will not count towards a cycle of treatment
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at screening. ECOG performance status of 2 at screening is allowed if the decrease in performance status is attributed to lymphoma
  • Disease response assessment of either complete response, partial response, or stable disease by Lugano 2014 criteria assessed by 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) (preferred) or contrast enhanced CT scans including neck/chest/abdomen/pelvis [37] after 2 cycles of induction therapy. If the participant has history of CNS disease, then he/she must have no history of or active parenchymal disease on magnetic resonance imaging (MRI)
  • Leptomeningeal alone disease is allowable if it is not clinically progressive or worsening from baseline assessment
  • A creatinine clearance (as estimated by direct urine collection, Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI], or Cockcroft-Gault Equation or institutional standard) ≥ 45 mL/min
  • Subjects of childbearing or child fathering potential must be willing to practice birth control from the time of enrollment on this study until the follow-up period of the study

Who cannot join

  • Unable to give informed consent
  • Any disease progression that occurs during the first 2 induction cycles
  • A creatinine clearance (as estimated by direct urine collection, Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI], or Cockcroft-Gault Equation or institutional standard) < 45 mL/min
  • Cardiac ejection fraction (EF) < 45% as determined by an echocardiogram (ECHO) or Multigated Radionuclide Acquisition scan (MUGA) (if range is provided, the upper value of the range may be used for assessing eligibility)
  • Resting O2 saturation < 92% on room air
  • Serum alanine aminotransferase (ALT) / aspartate aminotransferase (AST) ≥ 5 times the Upper Limit of Normal (ULN) for age
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  • Total bilirubin >1.5 mg/dL, except in individuals with Gilbert's syndrome
  • Absolute neutrophil count (ANC) < 1000/μL unless related to bone marrow infiltration by mantle cell lymphoma. No short-acting granulocyte colony-stimulating factor (G-CSF) use within 7 days of ANC evaluation
  • Platelet count < 50,000/µL unless related to bone marrow infiltration or hypersplenism by mantle cell lymphoma. No transfusions within 7 days of assessment.
  • Absolute CD3 count < 50/μL at screening
  • Absolute lymphocyte count (ALC) < 100/μL within 7 days of apheresis
  • Known history of infection with human immunodeficiency virus (HIV)
  • Known active infection with hepatitis B (hepatitis B surface antigen [HBsAg] positive). If there is a history of treated hepatitis B, the viral load must be polymerase chain reaction (PCR) negative; antiviral prophylaxis is required if HBsAg negative and anti-hepatitis B core (HBc) positive
  • Known active infection with hepatitis C virus (anti-HCV antibody positive). If patient has a positive hepatitis C antibody, the viral load must be undetectable per quantitative PCR and/or nucleic acid testing
  • No seizure history within 6 months prior to enrollment
  • Known history of cerebral vascular accident (CVA) within prior 12 months
  • Known history or presence of autoimmune CNS disease, such as multiple sclerosis, optic neuritis or other immunologic /or inflammatory diseases
  • Presence of active CNS disorder that, in the judgment of the investigator, may impair the ability to evaluate neurotoxicity
  • Uncontrolled bacterial, viral, or fungal infection at the time of enrollment.
  • Uncontrolled is defined as currently taking medication and with progression or no clinical improvement on adequate medical treatment
  • Pregnant or breast-feeding woman
  • Previous or concurrent malignancy with the following exceptions:
  • Adequately treated basal cell or squamous cell carcinoma (adequate wound healing is required prior to study entry)
  • In situ carcinoma of the cervix or breast, treated curatively and without evidence of recurrence for at least 2 years prior to the study
  • Adequately treated breast or prostate carcinoma on hormonal therapies such as Lupron or tamoxifen and in clinical remission of ≥ 2 years -or- low-grade untreated prostate cancer under observation
  • A primary malignancy which has been completely resected / treated with curative intent and in complete remission of ≥ 2 years
  • Subjects with prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with safety and efficacy assessment are eligible for this trial after discussion with protocol chair or protocol officer
  • Severely immunocompromised participants e.g. due to current systemic treatment of non-neurologic autoimmune disease (e.g. Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus)
  • Medical condition requiring prolonged use of systemic corticosteroids equivalent to prednisone >10 mg/day.
  • History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant cardiac disease within 6 months of enrollment
  • For systemic therapy or radiation therapy, at least 2 weeks or 5 half-lives, whichever is shorter, must have elapsed at the time of scheduled leukapheresis
  • BTKis can be continued through apheresis until one day prior to start of lymphodepletion
  • Baseline neurologic deficits that would interfere with therapy or monitoring, determined using Immune Effector Cell-Associated Encephalopathy (ICE) Assessment at baseline
  • History of severe immediate hypersensitivity reaction to any of the agents in this study
  • Refusal or inability to participate in additional lentiviral gene therapy long-term follow-up (LTFU) protocol
  • Prior CAR-T therapy for any indication or systemic gene-modifying therapy for B cell lymphoma
  • Prior allogeneic stem cell transplant for any indication.
  • Prior bispecific T cell engaging (BITE) antibodies for cancer therapy
  • Prior T cell receptor-engineered T cell therapy

Trial locations and contacts

No sites are listed yet. Contact the study team or a site near you to ask about taking part.

Sadie Swift contact

617-218-0044

clinicaltrials@miltenyi.com

Erick Flores contact

617-218-0044

clinicaltrials@miltenyi.com

About this study

Official title: Phase II Multicenter Trial of MB-CART2019.1 (Zamtocabtagene Autoleucel) Therapy as Frontline Consolidation for High-Risk Mantle Cell Lymphoma

FRONTIER is a prospective, single arm, open label, multi-center, Phase II study of MB-CART2019.1 (Zamtocabtagene Autoleucel) therapy as frontline consolidation for high-risk Mantle Cell Lymphoma (MCL) participants

Read the detailed description

This is a prospective, single arm, open label, multi-center, Phase II study of MB-CART2019.1 (Zamtocabtagene Autoleucel) therapy as frontline consolidation for high-risk Mantle Cell Lymphoma participants. Participants will be enrolled on the study after diagnosis and before the end of their second cycle of induction therapy.

Eligible patients will receive a single intravenous infusion of MB-CART2019.1 cells at a dose of 2.5x10^6 cells/kg following lymphodepleting chemotherapy. The goal is 52 participants in total who receive MB-CART2019.1 therapy. Additional participants may be screened, consented, registered, and treated in order to reach accrual goals. Participants will be followed on the trial for 1-year post-infusion. Assessment of survival annually through 15 years after infusion will be completed using the CIBMTR infrastructure.

Being tested
zamtocabtagene autoleucel (MB-CART2019.1), Cyclophosphamide, Fludarabine
Keywords
CD19/CD20-directed CAR-T Cells, Zamtocabtagene autoleucel, B-Cell Non-Hodgkin Lymphoma, Chimeric Antigen Receptor, CAR, CAR-T Cell, Lymphoma, Non-Hodgkin, Lymphoma, B-Cell, MCL, Immunotherapy, T cell infusion, High-risk, Mantle Cell Lymphoma, Frontline, TP53
Medical subject headings
Lymphoma, Mantle-Cell, Lymphoma, B-Cell, Lymphoma, Non-Hodgkin

What participants receive

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

  • zamtocabtagene autoleucel (MB-CART2019.1)Biological

    chimeric antigen receptor T-cell (CAR-T) therapy

  • CyclophosphamideDrug

    Lymphodepleting chemotherapy

  • FludarabineDrug

    Lymphodepleting chemotherapy

Study groups in NCT07569965
Study groupRoleWhat they receive
Single, open labelExperimentalNot described
Receives: Biological: zamtocabtagene autoleucel (MB-CART2019.1); Drug: Cyclophosphamide; Drug: Fludarabine

What is being measured

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

  1. Progression-free survival (PFS)

    The primary endpoint is PFS at 1-year following MB2019.1 CAR T cell infusion. PFS is defined as the time interval from CAR T cell infusion until a PFS event occurs.

    Measured: 1 year post-infusion

Secondary outcomes (7)

  1. Treatment Response

    Treatment response will be assessed using Lugano Criteria (Cheson et al, 2014). Both best overall response and Day 90 response following CAR T cell infusion will be evaluated.

    Measured: 1 year

  2. Overall Survival (OS)

    Events for OS include deaths from any cause. OS is defined as the time interval from CAR T cell infusion until death.

    Measured: 1 year post-infusion

  3. Duration of Complete Response (DOCR)

    DOCR is defined as the time from a participant's first achieving a CR until either a disease progression occurs per 2014 Lugano or IPCG criteria or death, whichever occurs first. DOCR will be evaluated in the set of participants who achieve a CR.

    Measured: 1 year post-infusion

  4. Non-relapse Mortality (NRM)

    Events for NRM include deaths without prior relapse/progression of the underlying malignancy. Relapse/progression is treated as a competing risk for NRM.

    Measured: 1 year post-infusion

  5. Relapse/progression

    Relapse/progression events will be determined per Lugano criteria.

    Measured: 1 year post-infusion

  6. IEC Related Toxicities

    CRS, ICANS, and IEC-HS will be determined per ASTCT criteria. The incidence and severity of each of these toxicities within 28 days of CAR T cell infusion will be reported. The incidence and severity of Grade 3 or higher ICANS occurring after Day 28 post-CAR T cell infusion will be reported.

    Measured: Up to 1 year post-infusion

  7. Event-free Survival (EFS)

    Events for EFS include clinical progression, additional anti-lymphoma treatment initiation (oral therapy, radiation) in the absence of clinical progression, and death. EFS is defined as the time interval from CAR T cell infusion until an EFS event occurs.

    Measured: 1 year-post infusion

Timeline

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

  1. First posted6 May 2026
  2. Study startSep 2026 (estimated)
  3. Primary completionSep 2029 (estimated)
  4. Study completionMar 2030 (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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
52 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07569965
Sponsor's protocol ID
PROJ112909
Other IDs
U24HL138660
Acronym
FRONTIER
Status last verified
Apr 2026
First submitted
28 Apr 2026
Last updated
6 May 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing zamtocabtagene autoleucel (MB-CART2019.1), Cyclophosphamide and Fludarabine in people with Mantle Cell Lymphoma (MCL), run by Miltenyi Biomedicine GmbH.

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 23 inclusion and 39 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: opening soon, as of the sponsor's last update on 6 May 2026. Status can change between updates, so confirm with the study contact before making plans.

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 phase mean?

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 Sadie Swift (617-218-0044, clinicaltrials@miltenyi.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression-free survival (PFS) (time frame: 1 year post-infusion). 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 NCT07569965.

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 6 May 2026.

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