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

NCT05360238 | Terminated Phase 1 DMC FDA Drug

• 2 other identifiers: MB106-CD20-0011R44CA265616-01
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 6

Brief Summary

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

Conditions

Follicular B-cell Non-Hodgkin's Lymphoma; Mantle Cell Lymphoma Recurrent; Mantle Cell Lymphoma Refractory; Small Lymphocytic Lymphoma, Relapsed; Waldenstrom's Macroglobulinemia Recurrent; Waldenstrom's Macroglobulinemia Refractory; Chronic Lymphoid Leukemia in Relapse; B-cell Lymphoma Refractory

Outcome Measures

Primary Outcomes (3)

• Phase 1: Primary objective

  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.

  24 months

• Phase 1: Primary objective

  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.

  24 months

• Phase 2: Primary objective

  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.

  24 months

Secondary Outcomes (6)

• Phase 1: Secondary objective

  24 months

• Phase 1: Secondary objective

  24 months

• Phase 1: Secondary objective

  24 months

• Phase 2: Secondary objective

  24 months

• Phase 2: Secondary objective

  24 months

Study Arms (7)

Phase 1: Patients with aggressive B-cell NHL including, but not limited to, DLBCL and MCL.

EXPERIMENTAL

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

Biological: MB-106

Phase 1: Patients with indolent NHL including, but not limited to, FL.

EXPERIMENTAL

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

Biological: MB-106

Phase 1: Patients with CLL/small lymphocytic lymphoma (SLL).

EXPERIMENTAL

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

Biological: MB-106

Phase 2: Patients with relapsed or refractory DLBCL

EXPERIMENTAL

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

Biological: MB-106

Phase 2: Relapsed or refractory FL

EXPERIMENTAL

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

Biological: MB-106

Phase 2: Basket - Relapsed or refractory B-cell NHL subtypes

EXPERIMENTAL

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

Biological: MB-106

Phase 2: Relapsed or refractory CLL/SLL

EXPERIMENTAL

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

Biological: MB-106

Interventions

MB-106 BIOLOGICAL

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

Phase 1: Patients with CLL/small lymphocytic lymphoma (SLL).; Phase 1: Patients with aggressive B-cell NHL including, but not limited to, DLBCL and MCL.; Phase 1: Patients with indolent NHL including, but not limited to, FL.; Phase 2: Basket - Relapsed or refractory B-cell NHL subtypes; Phase 2: Patients with relapsed or refractory DLBCL; Phase 2: Relapsed or refractory CLL/SLL; Phase 2: Relapsed or refractory FL

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• For Phase 1: Patient must have relapsed or refractory B-cell NHL (with the exception of Burkitt lymphoma and lymphoblastic lymphoma) or CLL that has progressed after standard therapies, including chemotherapy and anti-CD20 antibody combinations and molecularly targeted therapies. Patients may also have undergone prior stem cell transplant and/or prior CD19-directed CAR-T cell therapy.
• For Phase 2: Patient must have the following:
• Arm 1E: Relapsed or refractory DLBCL, including high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements, primary mediastinal large B-cell lymphoma and transformed FL. All patients must have progressed after at least 2 lines of therapy, including induction therapy with an anthracycline-based regimen with anti-CD20 antibody, as well as a second systemic therapy. Patients may have also received prior stem cell transplant and/or CD19-directed CAR-T therapy.
• Arm 2E: Relapsed or refractory FL. All patients must have progressed after at least 2 lines of therapy. Patients may have also received prior stem cell transplant and/or CD19-directed CAR-T therapy.
• Arm 2E-Basket: Relapsed or refractory B-cell NHL subtypes that have progressed after available therapies. This "basket" arm will include but is not limited to MCL, MZL, WMG, Burkitt and Burkitt-like lymphoma, and HCL. Patients may have also received prior stem cell transplant and/or CD19-directed CAR-T therapy.
• Arm 3E: Relapsed or refractory CLL/SLL All patients must have progressed after prior Bruton's tyrosine kinase (BTK) and/or BCL-2 directed therapy. Patients may have also progressed or have been intolerant to prior BTK and anti-CD20 antibody therapy. Patients may have also received prior stem cell transplant and/or CD19 CAR-T therapy.
• For patients treated with prior CD19-directed CAR-T therapy (all arms): relapsed from PR or CR of ≥ 3 months' duration with CD19-positive or -negative disease, or relapsed from PR or CR at any time with CD19-negative disease.
• For patients treated with prior CD19-directed CAR-T therapy, the peripheral blood absolute CD19+ B-cell count, as measured by flow cytometry, has recovered to at least 20 cells/μl.
• For patients with NHL, at least 1 measurable lesion according to the revised International Working Group Response Criteria for Malignant Lymphoma. Patients with Waldenstrom macroglobulinemia may qualify for enrollment based on a measurable lesion or an elevated IgM level \>0.5 g/dL.
• For patients with CLL, diagnosis of CLL that meets published diagnostic criteria. Measurable disease is not required.
• Evidence of CD20 expression on the tumor specimen obtained from the original diagnostic biopsy or another tissue biopsy performed prior to enrollment into this study.
• At least 2 weeks or 5 half-lives, whichever is shorter, have elapsed since any prior non-investigational systemic therapy before the patient's planned leukapheresis, with the exception of prior BTK inhibitor therapy, which can continue until day -6 (1 day prior to lymphodepletion). At least 6 months have elapsed since the last administration of bendamustine before patient's planned leukapheresis.
• Males and females ≥18 years of age at the time of consent.
• Capable of understanding, willing to comply with, and voluntarily sign and date an informed consent form prior to the conduct of any study related assessments/procedures.
• Able to adhere to the study visit schedule and other protocol requirements.

You may not qualify if:

• Patients who meet ANY of the following criteria will be excluded from the study. No exemptions will be granted.:
• Previous treatment with anti-CD20 or anti-CD19 therapy (including antibodies, antibody-drug conjugates \[ADCs\], bispecific antibodies, etc.) or any investigational agent within 4 weeks before leukapheresis.
• Concurrent known additional malignancy that is progressing and/or requires active treatment. Exceptions include squamous or basal cell carcinoma of the skin, superficial bladder cancer, and prostate cancer not requiring treatment.
• Presence of active acute or chronic Graft versus Host Disease (GVHD).
• Active central nervous system (CNS) lymphoma, including primary CNS lymphoma.
• Corticosteroid dependence on doses greater than physiological replacement, i.e., requirement for prednisone \> 7.5 mg/day or hydrocortisone ≥ 12 mg/m2/day.
• Ongoing prior therapy-related toxicities ≥ Grade 2, according to the Common Toxicity Criteria for Adverse Events (CTCAE), version 5.0, with the exception of alopecia or vitiligo or Grade 2 peripheral neuropathy.
• Active systemic infections, active, uncontrolled coagulation or bleeding disorders, or other active, uncontrolled major medical illnesses of the respiratory or immune system.
• Simple upper respiratory tract infection, uncomplicated bacterial pharyngitis and/or urinary tract infection are permitted if responding to active treatment and after consultation with the study Medical Monitor.
• Cardiac involvement with lymphoma, including pericardial involvement and malignant pericardial effusion.
• Significant cardiovascular diseases within the past 6 months including uncontrolled congestive heart failure (\>New York Heart Association class II), myocardial infarction, unstable angina, or uncontrolled arrhythmia. However, patients with ischemic heart disease who have had acute coronary syndrome, myocardial infarction and/or revascularization \> 6 months before Screening, who are without cardiac symptoms, may enroll.
• Requirement for urgent therapy due to tumor mass effects such as bowel obstruction or blood vessel compression.
• Documented human immunodeficiency virus (HIV) infection or any form of primary immunodeficiency, such as severe combined immunodeficiency disease.
• Known active infection with hepatitis B, hepatitis C, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), or other viral infections requiring systemic therapy.
• History of autoimmune disease (e.g., Crohn's disease, rheumatoid arthritis, systemic lupus) resulting in end organ injury or requiring systemic immunosuppression/systemic disease modifying agents within the previous 2 years.

Sponsors & Collaborators

• Mustang Bio: lead
• National Cancer Institute (NCI): collaborator

Study Sites (6)

UC Irvine Health - Chao Family Comprehensive Cancer Center

Orange, California, 92868-3201, United States

Location

Massachusetts General Hospital (MGH)

Boston, Massachusetts, 02114, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

University of Rochester Medical Center

Rochester, New York, 14642, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell; Recurrence

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Mazyar Shadman, MD

  Fred Hutchinson Cancer Center

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 14, 2022
• First Posted: May 4, 2022
• Study Start: May 24, 2022
• Primary Completion: April 12, 2024
• Study Completion: April 12, 2024
• Last Updated: July 22, 2024

Record last verified: 2023-12

Locations

US (6)