Neoplasms

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Rare Diseases

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Leukemia, Lymphoid

Lymphoma, Non-Hodgkin

Leukemia, Lymphocytic, Chronic, B-Cell

Lymphoma, B-Cell

Neoplasms by Histologic Type

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Chronic Disease

Disease Attributes

Chronic Graft Versus Host Disease

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Antineoplastic Agents

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All Drugs and Chemicals

Cyclophosphamide

Fludarabine

Fludarabine phosphate

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

1 x 10\^6 chimeric antigen receptor (CAR) T cells per kg body weight.

In this study, PBCAR20A, allogeneic anti-cluster of differentiation (CD20) CAR T Cells, is used to treat patients with relapsed or refractory (r/r) CD20+ Non-Hodgkin Lymphoma (NHL) or r/r Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL).

Route of Administration: Intravenous infusion (IV)

Lymphodepletion Conditioning: Lymphodepletion will be conducted several days prior to PBCAR20A infusion. A combination of fludarabine and cyclophosphamide will be used for lymphodepletion.

Single dose of Allogeneic Anti-CD20 CAR T cells will be infused, and a classic "3+3" dose escalation will be applied.

PBCAR20A

Fludarabine is used for lymphodepletion (30 mg/m\^2/day, Days -5 to -3).

Cyclophosphamide is used for lymphodepletion (500 mg/m\^2/day, Days -5 to -3).

Alan List, MD

This is a Phase 1/2a, nonrandomized, open-label, parallel assignment, single-dose, dose-escalation, and dose-expansion study to evaluate the safety and clinical activity of PBCAR20A in adult subjects with r/r B-cell NHL or r/r CLL/SLL.

This is a multicenter, nonrandomized, open-label, parallel assignment, single-dose, dose-escalation, and dose-expansion study to evaluate safety, tolerability, clinical activity, and find an appropriate dose to optimize safety and efficacy of PBCAR20A in subjects with relapsed/refractory (r/r) CD20+ Non-Hodgkin Lymphoma (NHL) or r/r Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL). Before initiating PBCAR20A, therapy, subjects will be administered lymphodepletion chemotherapy composed of fludarabine and cyclophosphamide. At Day 0 of the Treatment Period, subjects will receive a single intravenous (IV) infusion of PBCAR20A. All subjects are monitored during the treatment period through Day 28. All subjects who receive a dose of PBCAR20A will be followed in a separate long-term follow-up (LTFU) study for 15 years after exiting this study.

Phase 1: Participants with r/r CD20+ B-cell NHL or r/r CLL/SLL will be enrolled to 3 escalating dose groups and treated sequentially, with the possibility of a single de-escalation. Within each dose group, at least 3 and at most 6 study participants will be treated with a single dose of PBCAR20A using a standard 3 + 3 design. The starting dose of PBCAR20A will be 1 × 10\^6 chimeric antigen receptor (CAR) T cells/kg body weight. Subsequent dose groups will be treated with escalating doses to a maximum dose of 480 × 10\^6 CAR T cells (flat dose). In the absence of dose-limiting toxicities (DLTs) (as described in Section 3.8 of the protocol), the dose will be increased using a fixed-dose scheme.

Phase 2: Study PBCAR20A-01 did not proceed into Phase 2.

Dose-escalation Study of Safety of PBCAR20A in Subjects With r/r NHL or r/r CLL/SLL

A Phase 1/2a, Open-label, Dose-escalation, Dose-expansion, Parallel Assignment Study to Evaluate the Safety and Clinical Activity of PBCAR20A in Subjects With Relapsed/Refractory (r/r) Non-Hodgkin Lymphoma (NHL) or r/r Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL)

The maximum tolerated dose (MTD) is the dose level at which fewer than 33% of patients experience a dose limiting toxicity (DLT) using a 3+3 strategy.

Dose-limiting toxicities (DLT) are certain Grade 3 and Grade 4 toxic reactions as defined by the protocol and CTCAE v5.0.

Objective response rate (ORR) is a measure of clinical activity as response in NHL by the revised Lugano Classification (Cheson et al, 2016) or a response in CLL/SLL by the International Workshop on Chronic Lymphocytic Leukemia 2018 guidelines.

Progression-free survival is defined as the duration (days) from Day 0 to disease progression or death.

Precision BioSciences, Inc.

Dose Level 1 of PBCAR20A CAR T Cells

Dose Level 2 of PBCAR20A CAR T Cells

Dose Level 3 of PBCAR20A CAR T Cells

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Michael Karg, Senior Director, Clinical Operations

All participants who received PBCAR20A CAR T Cells at any dose level

PBCAR20A CAR T Cells

All participants. The participant who was dosed twice at Dose Level 3 (DL3) was counted as 2 individual participants.

Maximum Tolerated Dose (MTD)

All participants. The participant who was dosed twice at DL3 was counted as 2 individual participants.

Number of Participants With Dose-Limiting Toxicities

Responders

Complete Response

Partial Response

Non-responders

Objective Response Rate

Progression-free Survival (PFS)

1 x 10\^6 CAR T cells per kg body weight.

In this study, PBCAR20A, allogeneic anti-CD20 CAR T Cells, is used to treat patients with relapsed or refractory (r/r) Non-Hodgkin Lymphoma (NHL) or r/r Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL).

Route of Administration: Intravenous infusion.

Lymphodepletion Conditioning: Lymphodepletion will be conducted several days prior to PBCAR20A infusion. A combination of fludarabine and cyclophosphamide will be used for lymphodepletion.

PBCAR20A: Single dose of Allogeneic Anti-CD20 CAR T cells will be infused, and a classic "3+3" dose escalation will be applied.

Fludarabine: Fludarabine is used for lymphodepletion (30 mg/m\^2/day, Days -5 to -3).

Cyclophosphamide: Cyclophosphamide is used for lymphodepletion (500 mg/m\^2/day, Days -5 to -3).

240 x 10\^6 CAR T cells (flat dose)

PBCAR20A: Single dose of Allogeneic Anti-CD20 CAR T cells will be infused, and a classic "3+3" dose escalation will be applied.

Fludarabine: Fludarabine is used for lymphodepletion (30 mg/m\^2/day, Days -5 to -3).

Cyclophosphamide: Cyclophosphamide is used for lymphodepletion (500 mg/m\^2/day, Days -5 to -3).

480 x 10\^6 CAR T cells (flat dose)

PBCAR20A: Single dose of Allogeneic Anti-CD20 CAR T cells will be infused, and a classic "3+3" dose escalation will be applied.

Fludarabine: Fludarabine is used for lymphodepletion (30 mg/m\^2/day, Days -5 to -3).

Cyclophosphamide: Cyclophosphamide is used for lymphodepletion (500 mg/m\^2/day, Days -5 to -3).

Overall Study

Heart and Blood Diseases

Recurrence

Lymphoma, Mantle-Cell

Waldenstrom Macroglobulinemia

Neoplasms, Plasma Cell

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hemorrhagic Disorders

Mantle Cell Lymphoma

MB-106, single intravenous infusion up to 3.3 x 10e7 chimeric antigen receptor t-cells (CAR-T cells)/kg

MB-106, single intravenous infusion up to 3.3 x 10e7 CAR-T cells/kg

MB-106, single intravenous infusion. Dose based upon outcome Phase 1.

T-cells derived from autologous leukapheresis that are genetically modified.

MB-106

Premier Research

Harmonie Strohl

Jeremy S. Abramson, M.D.

M. Lia Palomba, MD

Kaitlyn Burrows

Patrick Reagan, MD

Cancer Awareness Department

SCCA Immunotherapy Intake

Mazyar Shadman, MD

Study to Assess the Safety, Tolerability and Efficacy of MB-106 in Patients with Relapsed or Refractory B-Cell NHL or CLL

This is a multicenter, Phase 1/2, open-label, non-randomized study of MB-106 in patients ≥18 years of age with selected CD20-expressing malignancies.

In both the Phase 1 and Phase 2 portions of the study, all patients must have evidence of CD20 expression.

In Phase 1, patients will be enrolled in 1 of 3 arms, based on their primary diagnosis, as follows:

* Arm 1: Patients with aggressive B-cell non-Hodgkin lymphoma (NHL) including, but not limited to, diffuse large B-cell lymphoma (DLBCL) and mantle cell lymphoma (MCL).
* Arm 2: Patients with indolent NHL including, but not limited to, follicular lymphoma (FL).
* Arm 3: Patients with chronic lymphocytic lymphoma (CLL)/small lymphocytic lymphoma (SLL).

In Phase 1, escalating MB-106 dose levels will be tested independently in each arm using a 3+3 design.

A total of up to 18 patients are anticipated to be treated in each independent arm in Phase 1, including 6 patients at the maximum tolerated dose (MTD; highest dose level at which ≤1 of 6 patients experiences a dose-limiting toxicity \[DLT\]), prior to proceeding to the Phase 2 portion of the study for each respective arm, where a total of up to 71 patients will participate in each independent arm.

An assessment of the safety and tolerability of the dose will be made by the Safety Review Committee (SRC) based on the data from the 28-day DLT observation period.

An SRC composed of Principal Investigators and Sponsor representatives will review the safety of each dose level for each arm prior to enrollment at the next dose level in the Phase 1 dose escalation part of study. This process will be repeated for each dose level within each arm until the MTD has been reached, and the recommended Phase 2 dose (RP2D) has been established for that arm.

In Phase 2, the following specific arms of relapsed or refractory CD20-positive B-cell NHL or CLL patients will be treated with MB-106 at the respective RP2D for each arm. Each arm will initially include up to 20 patients:

* Arm 1 Expansion (E): Relapsed or refractory DLBCL, including high-grade B-cell lymphoma with MYC and B-cell lymphoma 2 (BCL2) and/or B-cell lymphoma 6 (BCL6) rearrangements, primary mediastinal large B-cell lymphoma and transformed FL.
* Arm 2E: Relapsed or refractory FL.
* Arm 2E-Basket: Relapsed or refractory B-cell NHL subtypes that have progressed after available therapies. This "basket" arm will include but will not be limited to MCL, marginal zone lymphoma (MZL), Waldenstrom's macroglobulinemia (WMG), Burkitt and Burkitt-like lymphoma, and hairy cell leukemia (HCL).
* Arm 3E: Relapsed or refractory CLL/SLL

Arms 1E, 2E and 3E of Phase 2 will have an interim efficacy analysis for futility prior to completion of recruitment to the arm. Arm 2E-Basket will be summarized descriptively only. Safety data from all arms will also be provided at this interim timepoint to the Data Safety Monitoring Board (DSMB) for review. Based on the results of the interim analysis, an additional 51 patients may be added to each of these arms.

Study to Assess Safety, Tolerability and Efficacy of MB-106 in Patients With Relapsed or Refractory B-Cell NHL or CLL

A Phase 1/2, Open Label, Multicenter Study to Assess the Safety, Tolerability and Efficacy of MB-106 in Patients With Relapsed or Refractory CD20+ B-Cell Non-Hodgkin Lymphoma or Chronic Lymphocytic Leukemia

The safety, tolerability, and feasibility of MB-106 in patients with relapsed or refractory CD20+ B-cell NHL or CLL.

Incidence of treatment-emergent AEs (TEAEs) as assessed by CTCAE v5.0, including serious adverse events (SAEs), therapy-related AEs, Grade 3 or 4 TEAEs, TEAEs with an outcome of death (i.e., Grade 5 TEAEs), and TEAEs leading to study discontinuation.

To determine the RP2D of MB-106 in each of the 3 arms in patients with relapsed or refractory CD20+ B-cell NHL or CLL.

The RP2D will be the highest MB-106 dose in each arm that is associated with fewer than 2 cases of DLT in 6 patients.

To assess the efficacy of MB-106 as measured by objective response rate (ORR) according to the Lugano Classification for Lymphomas for patients with NHL. For patients with CLL, ORR will be assessed according to the 2018 Modified International Workshop for Chronic Lymphocytic Leukemia National Cancer Institute-Working Group. ORR will be determined by the percentage of patients achieving complete remission (CR) or partial remission (PR) as their best response. Radiology scans will be assessed for response by an Independent Central Reviewer.

To assess the efficacy of MB-106 as measured by objective response rate (ORR) according to the Lugano Classification for Lymphomas for patients with NHL. For patients with CLL, ORR will be assessed according to the 2018 Modified International Workshop for Chronic Lymphocytic Leukemia National Cancer Institute-Working Group for patients with CLL. ORR will be determined by percentage of patients achieving complete remission (CR) or partial remission (PR) as their best response.

To assess the efficacy of MB-106, as measured by duration of response (DOR), progression-free survival (PFS), and overall survival (OS).

To assess the total number of patients with minimal residual disease (MRD) in CLL patients.

To assess the safety, tolerability, and feasibility of MB-106 in patients with relapsed or refractory CD20+ B-cell NHL or CLL.

Incidence of treatment-emergent AEs (TEAEs) as assessed by CTCAE v5.0, including serious adverse events (SAEs), therapy-related AEs, Grade 3 or 4 TEAEs, TEAEs with an outcome of death (i.e., Grade 5 TEAEs), and TEAEs leading to study discontinuation.

Total number of patients with minimal residual disease (MRD) in CLL patients.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Dose-escalation Study of Safety of PBCAR20A in Subjects With r/r NHL or r/r CLL/SLL	NCT04030195	Non-Hodgkin's L... Chronic Lymphoi... Non-Hodgkin's L... Chronic Lymphoc... Lymphoma, Non-H... Leukemia, Lymph... B-cell Chronic ... B-cell Non Hodg... Small Lymphocyt...	PBCAR20A Fludarabine Cyclophosphamid...	18 Years -	Precision BioSciences, Inc.
Study to Assess Safety, Tolerability and Efficacy of MB-106 in Patients With Relapsed or Refractory B-Cell NHL or CLL	NCT05360238	Follicular B-ce... Mantle Cell Lym... Mantle Cell Lym... Small Lymphocyt... Waldenstrom's M... Waldenstrom's M... Chronic Lymphoi... B-cell Lymphoma...	MB-106	18 Years -	Mustang Bio
Study to Assess Safety, Tolerability and Efficacy of MB-106 in Patients With Relapsed or Refractory B-Cell NHL or CLL	NCT05360238	Follicular B-ce... Mantle Cell Lym... Mantle Cell Lym... Small Lymphocyt... Waldenstrom's M... Waldenstrom's M... Chronic Lymphoi... B-cell Lymphoma...	MB-106	18 Years -	Mustang Bio
Study to Assess Safety, Tolerability and Efficacy of MB-106 in Patients With Relapsed or Refractory B-Cell NHL or CLL	NCT05360238	Follicular B-ce... Mantle Cell Lym... Mantle Cell Lym... Small Lymphocyt... Waldenstrom's M... Waldenstrom's M... Chronic Lymphoi... B-cell Lymphoma...	MB-106	18 Years -	Mustang Bio
Dose-escalation Study of Safety of PBCAR20A in Subjects With r/r NHL or r/r CLL/SLL	NCT04030195	Non-Hodgkin's L... Chronic Lymphoi... Non-Hodgkin's L... Chronic Lymphoc... Lymphoma, Non-H... Leukemia, Lymph... B-cell Chronic ... B-cell Non Hodg... Small Lymphocyt...	PBCAR20A Fludarabine Cyclophosphamid...	18 Years -	Precision BioSciences, Inc.

Spots Global Cancer Trial Database for chronic lymphoid leukemia in relapse