A Phase I/II Study to Evaluate the Safety of Cellular Immunotherapy Using Autologous T Cells Engineered to Express a CD20-Specific Chimeric Antigen Receptor for Patients With Relapsed or Refractory B Cell Non-Hodgkin Lymphomas

NCT03277729 | Active Not Recruiting Phase 1 Results DMC FDA Drug

• 3 other identifiers: 9738NCI-2017-01595RG9217017
• Study Type: interventional
• Target: 53
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this research is to find the best dose of genetically modified T-cells, to study the safety of this treatment, and to see how well it works in treating patients with B cell non-Hodgkin lymphoma that has come back (relapsed) or did not respond to previous treatment (refractory).

Conditions

Recurrent B-Cell Non-Hodgkin Lymphoma; Recurrent Chronic Lymphocytic Leukemia; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Follicular Lymphoma; Recurrent Lymphoplasmacytic Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Refractory B-Cell Non-Hodgkin Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Follicular Lymphoma; Refractory Lymphoplasmacytic Lymphoma; Refractory Mantle Cell Lymphoma; Refractory Transformed Non-Hodgkin Lymphoma; Recurrent Transformed B-Cell Non-Hodgkin Lymphoma; Recurrent Transformed Chronic Lymphocytic Leukemia; Refractory Marginal Zone Lymphoma; Refractory Transformed B-Cell Non-Hodgkin Lymphoma; Refractory Transformed Chronic Lymphocytic Leukemia; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Small Lymphocytic Lymphoma; Recurrent Central Nervous System Lymphoma; Refractory Central Nervous System Lymphoma

Keywords

Lymphoid Leukemia; Non-Hodgkin's Lymphoma

Outcome Measures

Primary Outcomes (1)

• Dose-limiting Toxicities (DLT) Rate

  Will be graded by Common Terminology Criteria for Adverse Events version 4.0. Observed DLT rates will be summarized based on the DLT-Evaluable analysis set. Outcome reported as count of participants in each arm who experienced a DLT.

  Up to 28 days

Secondary Outcomes (4)

• Complete Remission

  Up to 15 years

• Progression-free Survival (PFS)

  Duration from study enrollment to progression or death due to any cause (whichever comes first), assessed up to 15 years

• Overall Survival (OS)

  Duration from study enrollment to death due to any cause, assessed up to 15 years

• Incidence of Adverse Events

  Up to 15 years

Study Arms (1)

Treatment (CD20-specific CAR T cell, chemotherapy)

EXPERIMENTAL

Patients undergo leukapheresis and may receive treatment after if needed for disease control. Patients then receive cyclophosphamide IV. Patients may also receive fludarabine IV. After 36-96 hours, patients receive CD20-specific CAR T cell infusion IV over 20-30 minutes.

Biological: Chimeric Antigen Receptor T-Cell Therapy; Drug: Cyclophosphamide; Other: Laboratory Biomarker Analysis; Procedure: Leukapheresis; Drug: Fludarabine Phosphate

Interventions

Chimeric Antigen Receptor T-Cell Therapy BIOLOGICAL

Given CD20 CAR T cell IV

Also known as: CAR T-cell therapy, CAR T Infusion, CAR T Therapy

Treatment (CD20-specific CAR T cell, chemotherapy)

Cyclophosphamide DRUG

Given IV

Also known as: (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, CP monohydrate, CTX, CYCLO-cell, Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR- 138719

Treatment (CD20-specific CAR T cell, chemotherapy)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (CD20-specific CAR T cell, chemotherapy)

Leukapheresis PROCEDURE

Undergo leukapheresis

Also known as: Leukocytopheresis, Therapeutic Leukopheresis

Treatment (CD20-specific CAR T cell, chemotherapy)

Fludarabine Phosphate DRUG

Given IV

Also known as: 2-F-ara-AMP, Beneflur, Fludara, Fludarabine-5''-Monophosphate, SH T 586

Treatment (CD20-specific CAR T cell, chemotherapy)

Eligibility Criteria

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

You may qualify if:

• Patients must have B-cell non-Hodgkin lymphoma or chronic lymphocytic leukemia/small lymphocytic lymphoma. Eligible lymphoma subtypes include (but not limited to): mantle cell, follicular, lymphoplasmacytic, marginal zone, transformed indolent B cell lymphoma (including transformed chronic lymphoid leukemia \[CLL\]), or diffuse large B cell lymphoma that has relapsed after a response to at least one prior therapy regimen or is refractory to prior therapy; patients with mantle cell lymphoma must have previously been treated with a Bruton tyrosine kinase (BTK) inhibitor and have either had disease progression, intolerance, or exposure to the drug for at least 3 months; patients with CLL/SLL are eligible if they had disease progression or intolerance to BTKis and/or a BCL-2 inhibitors; they are also required to have been treated with the other agent for at least 3 months (i.e. patients with progression/intolerance to BTKi need to be treated with a BCL-2 inhibitor for at least 3 months, and patients with progression/intolerance to BCL-2 inhibitor need at least 3 months of exposure to a BTKi); patients with de novo diffuse large B-cell lymphoma (DLBCL) must meet one of the following criteria:
• Biopsy-proven refractory disease after a frontline regimen containing both an anthracycline and rituximab or other anti-CD20 antibody (i.e. "primary refractory"), where any disease recurring within 6 months of completion of the regimen is considered refractory
• Relapsed or refractory disease after at least one of the following:
• At least 2 lines of therapy (including at least one with an anthracycline and anti-CD20 antibody)
• Autologous stem cell transplant
• Allogeneic stem cell transplant
• Patients with large cell lymphoma transformed from indolent lymphomas are eligible if previously treated with anthracycline containing regimen for either the indolent or large cell histology
• Patients with central nervous system (CNS) lymphoma need to meet one of the following criteria:
• Primary CNS lymphoma:
• Progressive disease after 3 cycles or an inadequate response after at least 4 cycles of a high-dose methotrexate (MTX) containing regimen in the opinion of the treating physician, OR
• Not eligible for MTX therapy due to commodities or tolerance issues per treating physician OR
• Recurrent disease after an initial response to MTX-based treatment
• Secondary CNS lymphoma:
• An inadequate rtesponse to at least 2 cycles of a MTX containing regimen, OR
• Recurrent disease after an initial response to MTX-based treatment

You may not qualify if:

• Active autoimmune disease requiring systemic immunosuppressive therapy
• Patients requiring corticosteroid therapy at a dose of 15 mg or more per day of prednisone or the equivalent; pulsed corticosteroid dose for disease control is acceptable
• Patients who are human immunodeficiency virus (HIV) seropositive
• Women who are pregnant or breastfeeding
• Significant cardiovascular diseases within the past 6 months including uncontrolled congestive heart failure (\> New York Heart Association \[NYHA\] class II), myocardial infarction, unstable angina, or uncontrolled arrhythmia
• History of severe immediate hypersensitivity reaction to cyclophosphamide or fludarabine
• History or presence of clinically relevant non-lymphoma central nervous system pathology, including seizures that are uncontrolled on anticonvulsant therapy (\>= 1 seizure in the last year), paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson disease, cerebellar disease, or psychosis
• Treatment with any investigational agent on a different clinical trial within 4 weeks prior to enrollment, unless the patient is documented to be unresponsive to the therapy and at least 3 half-lives have elapsed prior to enrollment
• Treatment with any anti-CD19 or anti-CD20 antibody or antibody-drug conjugate therapy within 4 weeks before enrollment
• Previous treatment with CD19-targeted CAR T cells that has resulted in ongoing B cell aplasia at the time of enrollment; patients that demonstrate recovery of normal B cells (\>= 20 B cells/ul) by flow cytometry at any point 28 days or later after CD19 CAR T cell infusion will be considered to have functional loss of CD19 CAR T cells and are potentially eligible
• Presence of active acute or chronic graft versus host disease (GVHD)
• Uncontrolled active infection (bacterial, fungal, viral, mycobacterial) not responding to treatment with intravenous antibiotics, antiviral or antifungal agents
• Patients with concurrent known additional malignancy that is progressing and/or requires active treatment; exceptions include squamous or basal cell carcinoma of the skin and low grade prostate carcinoma (Gleason grade =\< 6). Maintenance anti-hormone therapies for breast or prostate cancers are allowed and are not considered active treatment
• Patients with blood or platelet transfusion within 1 week prior to signing Consent A, or with platelets \< 50,000/mm\^3, neutrophils \< 750/mm\^3, or hemoglobin \< 8.5 g/dL, unless the cytopenias are considered by the treating physician to be largely due to marrow involvement by lymphoma

Sponsors & Collaborators

• Fred Hutchinson Cancer Center: lead
• Mustang Bio: collaborator

Study Sites (1)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

Related Publications (1)

• Ernst M, Oeser A, Besiroglu B, Caro-Valenzuela J, Abd El Aziz M, Monsef I, Borchmann P, Estcourt LJ, Skoetz N, Goldkuhle M. Chimeric antigen receptor (CAR) T-cell therapy for people with relapsed or refractory diffuse large B-cell lymphoma. Cochrane Database Syst Rev. 2021 Sep 13;9(9):CD013365. doi: 10.1002/14651858.CD013365.pub2.

  PMID: 34515338 DERIVED

MeSH Terms

Conditions

Lymphoma, B-Cell; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Follicular; Lymphoma, B-Cell, Marginal Zone; Lymphoma, Mantle-Cell; Leukemia, Lymphoid; Lymphoma, Non-Hodgkin

Interventions

Immunotherapy, Adoptive; Cyclophosphamide; Leukapheresis; fludarabine phosphate

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Adoptive Transfer; Immunization, Passive; Immunization; Immunotherapy; Immunomodulation; Biological Therapy; Therapeutics; Immunologic Techniques; Investigative Techniques; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Cytapheresis; Blood Component Removal; Leukocyte Reduction Procedures; Cell Separation; Cytological Techniques; Clinical Laboratory Techniques

Results Point of Contact

• Title: Mazyar Shadman
• Organization: Fred Hutchinson Cancer Center

mshadman@fredhutch.org

206-667-4216

Study Officials

• Mazyar Shadman

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: September 7, 2017
• First Posted: September 11, 2017
• Study Start: December 5, 2017
• Primary Completion: March 29, 2024
• Study Completion (Estimated): March 1, 2039
• Last Updated: January 5, 2026
• Results First Posted: April 16, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)