T Cells Expressing Fully-human Anti-CD19 and Anti-CD20 Chimeric Antigen Receptors for Treating B-cell Malignancies and Hodgkin Lymphoma

NCT04160195 | Terminated Phase 1 Results FDA Drug

• 2 other identifiers: 20000820-C-0008
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

Background:

• Cluster of differentiation 19 (CD19) and cluster of differentiation 20 (CD20) are often found on certain cancer cells. Researchers think that a person's T cells can be modified in a lab to kill cells that have CD19 and CD20 on the surface. Objective:
• To see if it is safe to give anti-CD19 and anti-CD20 CAR T cells to people with a B cell cancer or Hodgkin lymphoma. Eligibility:
• People ages 18 and older with a B cell cancer or Hodgkin lymphoma that has not been controlled with standard therapies Design:
• Participants will be screened under protocol 01C0129 with:
• Medical history
• Physical exam
• Blood and heart tests
• Bone marrow biopsy: A needle is inserted into the participant's hip bone to remove a small amount of marrow. Scans
• Participants will have apheresis: Blood will be removed through a vein. The blood with circulate through a machine that removes the T cells. The rest of the blood will be returned to the participant.
• Once a day for 3 days before they get the T cells, participants will receive chemotherapy through a vein.
• Participants will receive the T cells through a vein. They will stay in the hospital for at least 9 days.
• Participants may have a lumbar puncture: A needle will remove fluid from the spinal cord.
• Participants may have a tumor biopsy.
• Participants will repeat the screening tests throughout the study.
• Participants will have follow-up visits 2 weeks after infusion; monthly for 4 months; at 6, 9, and 12 months; every 6 months for 3 years; and then annually for 5 years. Participants will then be contacted annually for 15 years.

Conditions

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

Keywords

Autologous T Cells Infusion; Hu1928-Hu20BB; Hodgkin Reed-Sternberg Cells; Adoptive T Cell Therapy; Gene Therapy

Outcome Measures

Primary Outcomes (1)

• Number of Participants Administered T Cells Expressing a Novel Fully- Human Anti-cluster of Differentiation 19 (CD19) and Anti-cluster of Differentiation 20 (CD20) Chimeric Antigen Receptors (CAR) Who Experienced a Dose-limiting Toxicity (DLT)

  A DLT are defined as toxicities assessed by the Common Terminology Criteria for Adverse Events v5.0 that are possibly, probably, or definitely attributable to protocol interventions and occurring between the first protocol treatment through 28 days after the CAR T-cell infusion.

  First protocol treatment through 28 days after the CAR T-cell infusion.

Secondary Outcomes (4)

• Percentage of Peak Blood Chimeric Antigen Receptors (CAR) T Cells

  119 days after CAR T-cell infusion

• Percentage of Peripheral Blood Mononuclear Cells (PBMC) of Chimeric Antigen Receptors (CAR) T Cells

  pretreatment and multiple days from day 1 to day 173 after infusion.

• Number of Participants With Clinical Response

  Approximately 1 year 5 months

• Last Time-Point at Which Chimeric Antigen Receptors (CAR) T Cells Were Detected in the Blood

  119 days after CAR T-cell infusion

Other Outcomes (2)

• Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0)

  Date treatment consent signed to date off study, approximately 7 months and 18 days.

• Maximum Tolerated Dose (MTD) of Chimeric Antigen Receptors (CAR) T Cells

  First protocol treatment through 28 days after the CAR T-cell infusion.

Study Arms (2)

1/Conditioning chemotherapy plus Chimeric Antigen Receptors (CAR) T-cells dose escalation

ACTIVE COMPARATOR

All participants will be receiving escalating dose of Anti-cluster of differentiation 19 (CD19) and anti-cluster of differentiation 20 (CD20) CAR T cells/kg + conditioning chemotherapy

Biological: Anti-cluster of differentiation 19 (CD19)-Chimeric Antigen Receptors (CAR) and Anti-cluster of differentiation 20 (CD20)-CAR T cells; Drug: Cyclophosphamide; Drug: Fludarabine

2/Conditioning chemotherapy plus Chimeric Antigen Receptors (CAR) T-cells expansion phase

ACTIVE COMPARATOR

Maximum tolerated dose (MTD) dose of Anti-cluster of differentiation 19 (CD19) and anti-cluster of differentiation 20 (CD20) CAR T cells/kg + Conditioning chemotherapy

Biological: Anti-cluster of differentiation 19 (CD19)-Chimeric Antigen Receptors (CAR) and Anti-cluster of differentiation 20 (CD20)-CAR T cells; Drug: Cyclophosphamide; Drug: Fludarabine

Interventions

Anti-cluster of differentiation 19 (CD19)-Chimeric Antigen Receptors (CAR) and Anti-cluster of differentiation 20 (CD20)-CAR T cells BIOLOGICAL

Dose-escalation trial starting dose: 0.66 x10\^6 CAR+ T cells/kg (weight-based dosing one time) (up to a maximum dose of 10x10\^6 CAR+ T cells/kg based on cohort) infuse on day 0

1/Conditioning chemotherapy plus Chimeric Antigen Receptors (CAR) T-cells dose escalation; 2/Conditioning chemotherapy plus Chimeric Antigen Receptors (CAR) T-cells expansion phase

Cyclophosphamide DRUG

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

Also known as: Cytoxan

1/Conditioning chemotherapy plus Chimeric Antigen Receptors (CAR) T-cells dose escalation; 2/Conditioning chemotherapy plus Chimeric Antigen Receptors (CAR) T-cells expansion phase

Fludarabine DRUG

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

Also known as: Fludara

1/Conditioning chemotherapy plus Chimeric Antigen Receptors (CAR) T-cells dose escalation; 2/Conditioning chemotherapy plus Chimeric Antigen Receptors (CAR) T-cells expansion phase

Eligibility Criteria

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

You may qualify if:

• MALIGNANCY CRITERIA:
• Note: As of approval of Amendment A, no patients with Hodgkin lymphoma can be enrolled until at least 6 patients with B-cell malignancies are treated without incidence of Guillain-Bare syndrome
• Patients must have any B-cell lymphoma, or chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), Gray-zone lymphoma, nodular lymphocyte-predominant Hodgkin lymphoma, or classical Hodgkin lymphoma with any cluster of differentiation 19 (CD19) or cluster of differentiation 20 (CD20) expression on Reed-Sternberg cells. Lower grade lymphomas or CLL transformed to diffuse large B-cell lymphoma (DLBCL) are potentially eligible as is primary mediastinal B-cell lymphoma and all other subtypes of DLBCL. Burkitt and mantle cell lymphoma are potentially eligible.
• For classical Hodgkin lymphoma only, a biopsy from any time from any institution that shows any CD19 or CD20 expression on Reed-Sternberg cells is adequate for eligibility. CD19 or CD20 expression on the Reed-Sternberg cells that is weak or only present on some Reed-Sternberg cells by immunohistochemistry is compatible with protocol eligibility.
• For all lymphoma types except for classical Hodgkin lymphoma, either CD19 or CD20 expression must be uniform. Uniform CD19 or CD20 expression is defined as no obvious lymphoma population lacking antigen expression is present. Antigen expression can be assessed by either immunohistochemistry or flow cytometry.
• Only when insufficient biopsy material is available to allow CD19 and CD20 expression assessment at the National Institutes of Health (NIH), CD19 and/or CD20 staining performed at another institution can be used
• DLBCL patients must have received at least two prior chemotherapy-containing regimens at least one of which must have contained doxorubicin and a monoclonal antibody. Follicular lymphoma patients must have received at least 2 prior regimens including at least 1 regimen with chemotherapy. All other B-cell lymphoma and leukemia patients must have had at least 1 prior chemotherapy-containing regimen. All patients with CLL or small lymphocytic lymphoma must have had prior treatment with ibrutinib or another signal transduction inhibitor and venetoclax.
• Hodgkin lymphoma patients must have:
• had at least 3 prior lines of therapy.
• had at least 1 prior cytotoxic chemotherapy-containing regimen.
• had prior exposure to brentuximab vedotin.
• had undergone autologous stem cell transplant or been transplant ineligible or refused autologous transplantation
• Eligibility will be expanded to include CD19 and CD20-negative classical Hodgkin lymphoma if any 2 patients with classical Hodgkin lymphoma and CD19/CD20 expression on Reed-Sternberg (RS) cells have durations of response 6 months or greater (responses could be partial responses (PRs) or complete responses (CRs) or a CR of 3 months or greater.
• All patients must have measurable malignancy as defined by at least one of the criteria below.
• Lymphoma or leukemia masses that are measurable (minimum 1.5 cm in largest diameter) by computed tomography (CT) scan is required for all diagnoses except CLL. All masses must be less than or equal to 10.0 cm in the largest diameter.

You may not qualify if:

• Patients that require urgent therapy due to tumor mass effects or spinal cord compression.
• Patients must not have received any anti-CD20 or anti-CD19 antibody products in the past 30 days prior to CAR T-cell infusion.
• Any history of receiving programmed death 1 (PD-1) or programmed death ligand 1 (PD-L1) inhibitors
• Patients that have active hemolytic anemia.
• Human immunodeficiency virus (HIV)-positive patients are excluded because HIV causes complicated immune deficiency and study treatment can pose more risks for these patients.
• Patients 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.
• Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the preparative chemotherapy on the fetus or infant.
• Pregnant women are excluded from this study because study therapy can cause fetal harm. Because there is potential risk for adverse events in nursing infants secondary to treatment of the mother with study therapy, breastfeeding should be discontinued if the mother is treated with study drugs.
• Active uncontrolled systemic infections (defined as infections causing fevers and infections requiring intravenous antibiotics when intravenous antibiotics have been administered for less than 72 hours), 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.
• Hospitalization within the 7 days prior to enrollment.
• Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease).
• Prior allogeneic stem cell transplant
• Systemic lymphoma treatment of any type and 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.
• History of severe immediate hypersensitivity reaction to any of the agents used in this study.
• Patients on systemic anticoagulant therapy except aspirin.

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

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

Interventions

Automobiles; Cyclophosphamide; fludarabine; 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, Lymphoid; Leukemia; Hematologic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Motor Vehicles; Transportation; Technology, Industry, and Agriculture; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Results Point of Contact

• Title: Dr. James N. Kochenderfer
• Organization: National Cancer Institute

kochendj@mail.nih.gov

240-760-6062

Study Officials

• James N Kochenderfer, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 8, 2019
• First Posted: November 12, 2019
• Study Start: December 20, 2019
• Primary Completion: June 11, 2021
• Study Completion: June 11, 2021
• Last Updated: February 15, 2022
• Results First Posted: February 15, 2022

Record last verified: 2022-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data will be shared before publication and at the time of publication or shortly thereafter indefinitely.
• Access Criteria: Data will be shared through ClinicalTrials.gov, BTRIS, approved outside collaborators under appropriate individual agreements, and publication and/or public presentations.

Locations

US (1)