Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Lymphoma, Large B-Cell, Diffuse

Lymphoma

Lymphoma, Non-Hodgkin

Lymphoma, Mantle-Cell

Lymphoma, Follicular

Lymphoma, B-Cell, Marginal Zone

Lymphoma, B-Cell

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

B-cell Lymphoma

Diffuse Large B-Cell Lymphoma

Lymphosarcoma

Mantle Cell Lymphoma

Follicular Lymphoma

Marginal Zone Lymphoma

All Drugs and Chemicals

Immunomodulating Agents

This is a rollover protocol designed to provide long-term follow-up to all subjects previously enrolled in Adicet Bio allogeneic γδ CAR T cell study.

Patients will be followed for up to 15 years post treatment of Adicet Bio allogeneic γδ CAR T cell investigational products.

No study drug is administered in this study. Patients who have received Adicet allogeneic γδ CAR T cell therapy will be evaluated in this trial for long-term safety and efficacy

ADI-001

The purpose of this study is to assess long-term side effects from subjects who receive an Adicet Bio γδ CAR T cell product. Subjects will join this study once they complete the parent interventional study. No additional study drug will be given, but subjects can receive other therapies for their cancer while they are being followed for long term safety in this study. For a period of 15 years from the first administration of Adicet Bio allogeneic γδ CAR T cell product, subjects will be assessed for long-term safety and survival through collection of data that include safety, efficacy, pharmacokinetics and immunogenicity.

This is a non-therapeutic, multi-center, long-term follow-up (LTFU) study of subjects who received an Adicet Bio allogeneic γδ CAR T cell product that has been genetically engineered to express the anti-CD20 CAR by transduction with a self-inactivating, replication incompetent gamma retroviral vector. The period of follow-up is 15 years after the administration of the γδ CAR T cell product.

The study involves up to 15 years post-infusion monitoring of subjects who have been exposed to a genetically engineered CAR in Adicet Bio clinical studies. Upon early termination/discontinuation or completion of the parent interventional study, subjects will enroll into this study. Collection of these data will further define the risk-benefit and efficacy profile Adicet allogeneic γδ CAR T cell investigational products.

This is an observational study, and the elements of the study design are per published guidelines for gene therapy medicinal products that utilize integrating viral vectors such as gamma retrovirus and it is important to evaluate any delayed adverse events after infusion with such products.

Test for RCR following treatment with Adicet Bio allogeneic CAR T cell products. Also will continue to follow immunogenicity assessments of Adicet Bio allogeneic CAR T cell products by using patients blood specimens to assess humoral as well as cellular responses to CAR T cell products. Persistence of ADI-001 will be measured in blood.

Long-term Follow-up Study of Allogeneic Gamma Delta (γδ) CAR T Cells

Long-term Follow-up Protocol for Subjects Treated With Adicet Allogeneic Gamma Delta (γδ) CAR T Cell Investigational Products

Occurrence of new Adverse Events of Special interests, Serious AEs and malignancies

Test for RCR following treatment with Adicet Bio allogeneic γδ CAR T cell products by QCR analysis

Defined as duration from dosing to undetectable levels of Adicet allogeneic γδ CAR T cell per microliter blood

Progression Free Survival by Lugano Criteria

Overall Survival from date of first treatment until date of death

Adicet Bio, Inc

Nervous System Diseases

Musculoskeletal Diseases

Symptoms and General Pathology

Autoimmune Diseases

Myasthenia Gravis

Muscle Weakness

Neuromuscular Diseases

Paresis

Asthenia

Muscular Diseases

Neuromuscular Manifestations

Neurologic Manifestations

Syndrome

Paraneoplastic Syndromes

Paraneoplastic Syndromes, Nervous System

Nervous System Neoplasms

Autoimmune Diseases of the Nervous System

Neurodegenerative Diseases

Neuromuscular Junction Diseases

Amino Acids

Antibodies

Autoantibodies

Immunoglobulins

Tyrosine

Cohort A: Infusion of MuSK-CAART at various dose levels with or without pre-treatment (6 groups planned).

Cohort B: Infusion of MuSK-CAART at the dose regimen selected from Part A.

Intravenous infusion of MuSK-CAART at different doses. Subjects may also receive MuSK-CAART following pre-treatment with CY, or CY plus FLU.

MuSK-CAART

Cabaletta Bio

Mani Nistor

Ali Habib, MD

Joshua Valdez

David Richman, MD

Andrew J Heim

Mazen Dimachkie, MD

Katie Lewis

Nizar Chahin, MD

Medical Director

Muscle-specific tyrosine kinase (MuSK) myasthenia gravis (MG) is a rare but potentially severe disease, in which patients develop pathogenic autoantibodies that specifically target the MuSK protein in the neuromuscular junction. This phase 1 study is being conducted to evaluate the safety of various dosing regimens of an investigational cell therapy, MuSK-CAART, that can be given to patients with anti-MuSK antibody positive Myasthenia Gravis (MuSK MG), who have active disease. Various dosing regimens of MuSK-CAART alone, in combination with cyclophosphamide (CY), and in combination with CY and fludarabine (FLU) will be evaluated. Treatment with MuSK-CAART may potentially lead to complete and durable remission of disease.

Open-label Study to Evaluate the Safety of Various Dosing Regimens of MuSK-CAART for MuSK Myasthenia Gravis

A Phase 1, Open-label, Safety and Dose-finding Study of Autologous Muscle-specific Tyrosine Kinase Chimeric Autoantibody Receptor T Cells (MuSK-CAART) in Subjects With Anti-MuSK-antibody-positive Myasthenia Gravis

Frequency and dose of concomitant therapies.

Measurement of clinical symptoms using the Myasthenia Gravis Activities of Daily Living (MG-ADL) assessment.

Measurement of clinical symptoms using the Quantitative Myasthenia Gravis (QMG) assessment.

Measurement of clinical symptoms using the Myasthenia Gravis Composite (MGC) assessment.

Measurement of Quality of Life using the MG-QOL-15r (Myasthenia Gravis Qualify of Life 15-item scale, revised) questionnaire.

Incidence of adverse events (AEs), including dose-limiting toxicities (DLTs) and AEs that are related to MuSK-CAART.

Total MuSK-CAART positive cells for each manufacturing run.

Percent of total cells for infusion that are CAAR (Chimeric Autoantibody Receptor)-transduced cells.

Cellular kinetics profile of MuSK-CAART after infusion.

Change in MuSK autoantibody titer compared to pre-infusion visit by clinically validated assay.

Central Nervous System Depressants

Other Dietary Supplements

Benzocaine

Tannic Acid

ALETA-001 will be administered intravenously (IV) every two weeks.

ALETA-001

Emma Ingleson

Sridhar Chaganti, Dr

Ram Malladi, Dr

Cathy Burton, Dr

William Townsend, Dr

Jane Norman, Dr

Adam Gibb, Dr

Carlos Arias, Dr

This is a Phase I/II multicentre, open-label trial designed to evaluate the efficacy, safety, tolerability and pharmacokinetics (PK) of a novel chimeric antigen receptor (CAR) T-cell engager, ALETA-001, administered by intravenous (IV) infusion as a single agent every 2 weeks in patients with relapsed non-Hodgkin lymphoma (NHL) who have failed to optimally respond to prior treatment with anti-CD19 CAR T-cell therapy. This first in human study is divided into 2 parts: a safety lead-in phase (Phase I) and a dose expansion phase (Phase II). Different dose levels of ALETA-001 will be evaluated in Phase I in order to define a recommended dosing level and schedule for Phase II. Phase II will further evaluate the safety, PK and therapeutic activity of ALETA-001.

A Phase I/II Trial of ALETA-001 for the Treatment of Participants With B-cell Malignancies

A Cancer Research Phase I/ II Trial of ALETA-001 in Participants Who Do Not Achieve or Maintain an Optimal Response to Anti-CD19 CAR T-cell Therapy for the Treatment of B-cell Malignancies

Individual de-identified patient data that underlie the results reported will be shared with researchers whose proposed use of the data is approved by a review committee of the Sponsor.

Determine a dose level that is deemed tolerable based on available safety and pharmacodynamic data.

DLTs will be assessed up to Day 28 and are defined as toxicities that meet pre-defined severity criteria and assessed as having a suspected relationship to study drug, and unrelated to disease, disease progression, intercurrent illness, or concomitant medications that occurs within the 28 days of the first dose of ALETA-001.

Related AEs are those considered by the investigator to be possibly, probably or highly probably related to ALETA-001. Events of cytokine release syndrome (CRS) and immune effector cell mediated neurotoxicity (ICANS) are graded according to the American Society for Transplantation and Cellular Therapy grading criteria. All other AEs are graded according to the Common Terminology Criteria for AEs (CTCAE) Version 5.0.

Best Overall Response according to Lugano criteria (Cheson, Journal of Clinical Oncology, 2014), the number of participants taking part in the Dose Expansion Phase with best overall response of complete response (CR), partial response (PR), no response or stable disease (SD/NR), and progressive disease (PD).

Median PFS measured from first dose of ALETA-001 to date of progression according to Lugano criteria or date of death without a previous progression recorded.

Median TTP measured from first dose of ALETA-001 to date of progression according to Lugano criteria. Participants who die without recorded progression will be censored.

Median OS measured from first dose of ALETA-001 to date of death due to any cause or to the date of censoring at the last time the participant was known to be alive.

Best Overall Response according to Lugano criteria, the number of participants taking part in the Safety Lead-in Phase with best overall response of complete response (CR), partial response (PR), no response or stable disease (SD), and progressive disease (PD).

Measurement of Cmax of ALETA-001 as appropriate.

Measurement of t1/2 of ALETA-001 as appropriate.

Measurement of AUC of ALETA-001 as appropriate.

Measurement of Vss of ALETA-001 as appropriate.

Measurement of CL of ALETA-001 as appropriate.

Aleta BioTherapeutics

Cancer Research UK

Antineoplastic Agents

Antirheumatic Agents

Cyclophosphamide

Fludarabine

Fludarabine phosphate

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

ADI-001 is administered via infusion with ascending dose levels as a single dose to determine the maximum tolerated dose (MTD) or maximum assessed dose (MAD) of ADI-001 (Part 1a).

ADI-001 is administered via infusion at MAD/MTD to evaluate the safety of multiple doses (Part 1b).

Dose Expansion ADI-001 is administered via infusion at the MTD/MAD to confirm recommended phase 2 dose (Part 2).

Adicet Medical Director

David Miklos, MD

Jay Spiegel, MD

Asad Bashey, MD

Umar Farooq, MD

Don A Stevens, MD

Matthew Cortese, MD

Houston Holmes, MD

Sattva Neelapu, MD

Krish Patel, MD

This is a Phase 1 dose escalation study following a 3+3 study design. The purpose of this study is to evaluate the safety and efficacy of ADI-001 in patients with B cell malignancies.

ADI-001 is an investigational immunotherapy composed of allogeneic gamma delta T cells that is being evaluated as a potential treatment for patients diagnosed with B cell malignancies who have relapsed or are refractory to at least two prior regimens. This first-in-human study will assess the safety and tolerability of ADI-001 and is designed to determine the maximum tolerated dose (MTD) or maximum assessed dose (MAD). Patients will be administered a single infusion or multiple infusions of ADI-001 cells. The study will include the following two parts:

Part 1 : dose escalation and extension. Parts 1a (escalation) and 1b (extension) will involve escalation and administration of single dose of ADI-001 and multiple doses of ADI-001.

Part 2 : dose expansion will involve dose administration of ADI-001 at MTD/MAD as determined in Part 1.

The study will also assess the pharmacokinetics and pharmacodynamics of ADI-001.

A Phase 1 Study of ADI-001 in B Cell Malignancies

A Phase 1 Safety and Efficacy Study of ADI-001 Anti-CD20 CAR-engineered Allogeneic Gamma Delta (γδ) T Cells in Adults With B Cell Malignancies

This primary endpoint will be used to determine the Maximum Tolerated Dose (MTD) or Maximum Assessed dose (MAD).

This primary endpoint will be used to determine the MTD/MAD of ADI-001

Defined as duration from Day 1 to undetectable levels of ADI-001 cells per microliter blood

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Long-term Follow-up Study of Allogeneic Gamma Delta (γδ) CAR T Cells	NCT04911478	Lymphoma, Folli... Lymphoma, Mantl... Marginal Zone L... Primary Mediast... Diffuse Large B... Lymphoma, Non-H...	ADI-001	18 Years -	Adicet Bio, Inc
Open-label Study to Evaluate the Safety of Various Dosing Regimens of MuSK-CAART for MuSK Myasthenia Gravis	NCT05451212	MuSK Myasthenia...	MuSK-CAART	18 Years -	Cabaletta Bio
A Phase I/II Trial of ALETA-001 for the Treatment of Participants With B-cell Malignancies	NCT06045910	Lymphoma, Non-H... Lymphoma, Large... Lymphoma, Mantl... Lymphoma, Folli... Lymphoma, B-Cel...	ALETA-001	16 Years -	Cancer Research UK
A Phase 1 Study of ADI-001 in B Cell Malignancies	NCT04735471	Lymphoma, Folli... Lymphoma, Mantl... Marginal Zone L... Primary Mediast... Diffuse Large B... Lymphoma, Non-H...	ADI-001 Fludarabine Cyclophosphamid...	18 Years -	Adicet Bio, Inc

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