Trial of Anti-CD19 and Anti-CD20 Bicistronic Chimeric Antigen Receptor T Cells for Treating B-Cell Malignancies

NCT05797233 | Active Not Recruiting Phase 1 FDA Drug

• 2 other identifiers: 10001524001524-C
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 1

Brief Summary

Background: About 23,000 people die from B-cell cancers in the US each year. These cancers, often called leukemia or lymphoma, affect a type of white blood cell called B cells. These cancers are difficult to treat, and the therapies used can have bad side effects. Researchers want to try a new type of treatment. This new treatment uses a patient s own immune cells (T cells) that are modified to carry genes (chimeric antigen receptor, or CAR T cells) to kill cancer cells. Objective: To test a treatment using CAR T cells in people with B-cell cancers. Eligibility: People aged 18 to 75 years with a B-cell cancer that has not been controlled with standard therapies. Design: Participants will be screened. They will have: Blood and urine tests. A needle will be inserted to draw a sample of tissue from inside the hip bone. For some patients, a needle will be inserted into their lower back to get a sample of the fluid around their spinal cord. A tumor biopsy might be needed. Imaging scans. Tests of their heart function. Participants will undergo apheresis: Blood will be drawn from a needle in an arm. The blood will pass through a machine that separates out the T cells. The remaining blood will be returned to the body through a second needle. Participants will receive 2 chemotherapy drugs once a day for 3 days. Participants will be admitted to the hospital for at least 9 days. Their T cells, now modified, will be infused back into their bloodstream through a tube placed in a large vein. Follow-up visits will continue for 5 years, but patients will need to stay in touch with the CAR treatment team for 15 year.

Conditions

Chronic Lymphocytic Leukemia; B-Cell Chronic Lymphocytic Leukemia; Lymphoma, B-Cell

Keywords

Immunotherapy; Autologous T Cells Infusion; Hu1928-Hu20BB; Adoptive T Cell Therapy; Gene Therapy

Outcome Measures

Primary Outcomes (1)

• Determine the safety and feasibility of administering T cells expressing a novel fully-human anti-CD19 and anti-CD20 CAR construct to patients with advanced B-cell malignancies.

  Adverse Events (AE) by type and grade of toxicity

  From time of lymphodepleting regimen through 30 days after the last CAR T infusion.

Secondary Outcomes (3)

• Assess complete response rate

  up to 5 years

• Assess overall response rate

  up to 5 years

• Assess duration of responses

  up to 5 years

Study Arms (2)

1/Conditioning chemotherapy plus CAR T-cells dose escalation

EXPERIMENTAL

Escalating dose of anti-CD19 and anti-CD20 CAR T- cells/kg + conditioning chemotherapy

Biological: Anti-CD19 and anti-CD20 bicistronic CAR T- cells; Drug: Cyclophosphamide; Drug: Fludarabine

2/Conditioning chemotherapy plus CAR T-cells expansion phase

EXPERIMENTAL

MTD dose or Optimal dose of Anti-CD19 and anti-CD20 CAR T- cells/kg + conditioning chemotherapy

Biological: Anti-CD19 and anti-CD20 bicistronic CAR T- cells; Drug: Cyclophosphamide; Drug: Fludarabine

Interventions

Anti-CD19 and anti-CD20 bicistronic CAR T- cells BIOLOGICAL

0.66x10\^6 CAR+ T - 10x10\^6 CAR+ T cells/kg (weight based dosing per cohort) infused on day 0

1/Conditioning chemotherapy plus CAR T-cells dose escalation; 2/Conditioning chemotherapy plus CAR T-cells expansion phase

Cyclophosphamide DRUG

500 mg/m\^2 IV infusion over 30 minutes on days -5, -4 and -3

1/Conditioning chemotherapy plus CAR T-cells dose escalation; 2/Conditioning chemotherapy plus CAR T-cells expansion phase

Fludarabine DRUG

30 mg/m\^2 IV infusion over 30 minutes administered immediately following the cyclophosphamide on days -5, -4,and -3

1/Conditioning chemotherapy plus CAR T-cells dose escalation; 2/Conditioning chemotherapy plus CAR T-cells expansion phase

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Malignancy criteria
• CD19 and or CD20 expression is required. For all lymphoma types, eligibility criteria are met if there is uniform expression of both CD19 and CD20. Eligibility criteria are also met with expression of either CD19 or CD20. CD19 and/or CD20 expression must be "uniform". "Uniform" CD19 or CD20 expression is defined by CD19 and/or CD20 antigen expression on lymphoma cells with no obvious lymphoma population lacking antigen expression. Antigen expression can be assessed by either immunohistochemistry or flow cytometry.
• Pathology confirmed B-cell malignancy. Only when insufficient biopsy material is available to allow CD19 and CD20 expression assessment at the NIH, CD19 and/or CD20 staining performed at another institution can be used.
• At least 14 days must elapse between the time of any prior systemic treatment (including corticosteroids) and protocol-required leukapheresis or start of protocol conditioning chemotherapy.
• At least sixty days must elapse from therapy with antibodies targeting CD19 or CD20 and CAR T-cell infusion.
• At least 180 days must elapse after any prior CAR T-cell therapy, but otherwise, prior CAR T-cell therapy is allowed.
• Participants with DLBCL (including all subtypes such as primary mediastinal B-cell lymphoma and high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangement) must have received at least two prior regimens at least one of which must have contained doxorubicin and an anti-CD20 monoclonal antibody.
• Follicular lymphoma participants must have received at least 2 prior regimens including at least 1 regimen with chemotherapy and 1 regimen with an anti-CD20 monoclonal antibody.
• Burkitt lymphoma participants must have had at least 1 prior cytotoxic chemotherapy- containing regimen that also contained an anti-CD20 monoclonal antibody.
• All participants with CLL or small lymphocytic lymphoma must have had at least 1 prior line of treatment, and these participants must have had progressive CLL/SLL after exposure to ibrutinib or another Bruton tyrosine kinase inhibitor and venetoclax.
• T-cell rich B-cell lymphoma is eligible if previously treated with at least 2 lines of therapy.
• Waldenstrom s macroglobulinemia/lymphoplasmacytic lymphoma patients are eligible if previously treated with at least 2 regimens including exposure to a monoclonal antibody, a bruton tyrosine kinase inhibitor, and cytotoxic chemotherapy.
• Participants with mantle cell lymphoma are eligible after receiving a Bruton tyrosine kinase (BTK) inhibitor, an anti-CD20 monoclonal antibody, and at least one of the following chemotherapy drugs: cytarabine, bendamustine, or an anthracycline.
• Other B-cell lymphoma types, including B-cell lymphoma unclassifiable with features intermediate between DLBCL and Hodgkin lymphoma (Gray zone), that are not specifically mentioned above are allowed if the participant has received at least 2 lines of therapy at least 1 of which must have contained cytotoxic chemotherapy.
• Primary central nervous system lymphoma patients are not eligible.

You may not qualify if:

• Participants that require urgent therapy due to tumor mass effects or spinal cord compression.
• Participants must not have received any anti-CD20 or anti-CD19 antibody products in the past 60 days prior to CAR T-cell infusion.
• Participants that have active hemolytic anemia.
• HIV-positive patients.
• Participants with second malignancies in addition to their B-cell malignancy are not eligible if the second malignancy has required treatment (including maintenance therapy) within the past 3 years or is not in complete remission. There are two exceptions to this criterion: successfully treated non-metastatic basal cell or squamous cell skin carcinoma.
• Currently pregnant (confirmed with beta-HCG serum or urine pregnancy test performed at screening) or breastfeeding.
• Active uncontrolled systemic infections (defined as infections causing fevers within 48 hours of the date of planned protocol chemotherapy start and infections requiring intravenous antibiotics when intravenous antibiotics have been administered for less than 72 hours at the time of protocol chemotherapy start).
• Active coagulation disorders or other major uncontrolled medical illnesses of the cardiovascular, respiratory, endocrine, renal, gastrointestinal, genitourinary or immune system, history of myocardial infarction, history of ventricular tachycardia or ventricular fibrillation, active cardiac arrhythmias (active atrial fibrillation is not allowed, resolved atrial fibrillation not requiring current treatment is allowed (anticoagulants count as current treatment), active obstructive or restrictive pulmonary disease, active autoimmune diseases such as rheumatoid arthritis.
• Significant neurologic disorders that are not completely and permanently resolved and not requiring current treatment.
• Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease).
• Prior allogeneic stem cell transplant
• Systemic corticosteroid steroid therapy of any dose greater than 5 mg/day or more of prednisone or equivalent is not allowed within 14 days prior to the required leukapheresis, or the initiation of the conditioning chemotherapy regimen. Corticosteroid creams, ointments, and eye drops are allowed.
• Participants on systemic anticoagulant therapy except aspirin.
• History of severe immediate hypersensitivity reaction to any of the agents used in this study.
• Active central nervous system/brain metastases or cerebrospinal fluid malignancy.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, B-Cell

Interventions

Cyclophosphamide; fludarabine

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; Lymphoma, Non-Hodgkin; Lymphoma

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• James N Kochenderfer, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: April 1, 2023
• First Posted: April 4, 2023
• Study Start: August 28, 2023
• Primary Completion (Estimated): December 30, 2028
• Study Completion (Estimated): December 30, 2029
• Last Updated: January 13, 2026

Record last verified: 2026-01-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Clinical data will be available during the study and indefinitely.
• Access Criteria: Clinical data will be made available via subscription to BTRIS and with the permission of the study PI

Locations

US (1)