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

  • STATUS
    Recruiting
  • End date
    Sep 24, 2026
  • participants needed
    287
  • sponsor
    Mustang Bio
Updated on 24 July 2022

Summary

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

Description

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.

Details
Condition 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
Treatment MB-106
Clinical Study IdentifierNCT05360238
SponsorMustang Bio
Last Modified on24 July 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

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 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 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 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 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 (IWG) Response Criteria for Malignant Lymphoma
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 systemic therapy before the subject's planned leukapheresis, with the exception of prior BTK inhibitor therapy, which can continue until day -6 (1 day prior to lymphodepletion)
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
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
Life expectancy of ≥ 16 weeks, as assessed by the Principal Investigator
All patients must meet all of the following laboratory criteria unless, in the opinion of the Investigator, the cytopenias are considered to be the result of marrow infiltration by lymphoma/CLL
Absolute neutrophil count (ANC) ≥ 0.75×10e9/L
Platelet count ≥ 75×10e9/L
Hemoglobin ≥ 8.5 g/dL
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 2.5× the upper limit of normal (ULN)
Calculated creatinine clearance ≥ 45.0 mL/minute as estimated by Cockcroft-Gault formula
Total bilirubin ≤ 1.5×ULN, unless due to suspected Gilbert's syndrome
Adequate pulmonary function, defined as ≤ Grade 1 dyspnea and oxygen saturation (SaO2)
≥ 92% on room air. If pulmonary function tests (PFTs) are performed based on
the clinical judgment of the treating physician, patients with forced
expiratory volume in 1 second (FEV1) ≥ 50% of predicted and diffusing capacity
for carbon monoxide (DLCO) (corrected) of ≥ 40% of predicted will be eligible
Left ventricular ejection fraction ≥ 50%, as determined by echocardiography (ECHO) or multi-gated acquisition scan (MUGA)
Females of childbearing potential must have a negative serum or urine pregnancy test at screening and negative serum or urine pregnancy test prior to initiation of the lymphodepletion regimen
If procreative potential exists, patient must agree to use a highly effective method of contraception from the start of the study until 1 year after the completion of lymphodepletion for females and 4 months after completion of lymphodepletion for males

Exclusion Criteria

Patients who meet ANY of the following criteria will be excluded from the study
Previous treatment with anti-CD20 or anti-CD19 therapy (including antibodies, antibody-drug conjugates [ADCs], bispecific antibodies, etc.) 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
If female, pregnant, planning to become pregnant, or breastfeeding
Any other clinically significant medical disease or condition that, in the Principal Investigator's opinion, may interfere with protocol adherence or the patient's ability to provide informed consent
Clear my responses

How to participate?

Step 1 Connect with a study center
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar

Primary Contact

site

0/250

Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider

Loading...

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 

 • 

Private

Reply by • Private
Loading...

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.
Loading...

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note