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Recruiting Phase 1

Anti-CD19 Chimeric Antigen Receptor T Cells for Treatment of Relapsed or Refractory Non-Hodgkin Lymphoma

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About this study

This study will assess safety and feasibility of infusing genetically modified autologous T cells transduced to express a chimeric antigen receptor targeting the B cell surface antigen Cluster of Differentiation 19 (CD19).

Condition
Refractory Non-Hodgkin Lymphoma, Burkitt Lymphoma, Mantle Cell Lymphoma, Follicular Lymphoma, Lymphoplasmacytic Lymphoma, Primary Mediastinal Large B Cell Lymphoma, Diffuse Large B Cell Lymphoma, Small Lymphocytic Lymphoma, Transformed Lymphoma, Non-Hodgkin Lymphoma
Tested
Fludarabine, Cyclophosphamide, anti-CD19 CAR-T cells
Sponsor
C. Babis Andreadis

Who can join

Age
18 years and older
Sex
All sexes
Healthy volunteers
Not accepted

Inclusion 32

  • Minimum age: 18 years
  • Study condition: Refractory Non-Hodgkin Lymphoma, Burkitt Lymphoma, Mantle Cell Lymphoma, Follicular Lymphoma, Lymphoplasmacytic Lymphoma, Primary Mediastinal Large B Cell Lymphoma, Diffuse Large B Cell Lymphoma, Small Lymphocytic Lymphoma, Transformed Lymphoma, Non-Hodgkin Lymphoma
  • THE DOSE ESCALATION COHORT IS CLOSED TO FURTHER ENROLLMENT.
  • Dose expansion Cohorts:
  • Cohort B (Burkitt):
  • Participants must have a diagnosis of relapsed or refractory Burkitt Lymphoma
  • Participants with Burkitt lymphoma must have relapsed or failed to respond to at least 1 prior line of multiagent chemoimmunotherapy with prior exposure to both an anti-CD20 antibody agent and an anthracycline.
  • No significant circulating disease, defined as an elevated total lymphocyte count above the upper limit of normal (ULN) due to the presence of malignant cells.
  • Participants must have measurable disease as defined below:
  • Participants with Burkitt Lymphoma must have Positron Emission Tomography (PET)-positive disease according to "Recommendations for Initial Evaluation, Staging, and Response Assessment of Hodgkin and Non-Hodgkin Lymphoma: The Lugano Classification"
  • Cohort M/W (Marginal/Waldenström):
  • Participants must have a diagnosis of relapsed or refractory Marginal Zone Lymphoma (MZL), or Lymphoplasmacytic Lymphoma (LPL)/Waldenström Macroglobulinemia (WM):
  • o Participants with indolent lymphomas (nodal or extranodal marginal zone lymphoma, and lymphoplasmacytic lymphoma) must have relapsed after or have been refractory to ≥ 2 prior lines of multi-agent chemoimmunotherapy including prior exposure to an anti-CD20 antibody and an alkylating agent.
  • o Participants with Marginal Zone Lymphoma or Lymphoplasmacytic Lymphoma/Waldenström Macroglobulinemia: must either have PET-positive disease according to "Recommendations for Initial Evaluation, Staging, and Response Assessment of Hodgkin and Non-Hodgkin Lymphoma: The Lugano Classification" or serum monoclonal immunoglobulin M (IgM) paraprotein \> 0.5 g/dL.
  • Participants with indolent lymphoma (Marginal Zone Lymphoma or Lymphoplasmacytic Lymphoma/Waldenström Macroglobulinemia) must have symptomatic disease or steady progression necessitating systemic treatment per investigator discretion.
  • In addition, all participants must meet the following criteria:
  • CD19-positive by either immunohistochemistry or flow cytometry analysis on any biopsy. If prior anti-CD19 therapy has been administered, CD19-positivity has to be re-established on the most recent biopsy.
  • Age ≥18 years at the time of consent.
  • Absolute lymphocyte count \> 100/UL.
  • Eastern Cooperative Oncology Group (ECOG) performance status \< 2.
  • Adequate organ function, defined as:
  • Adequate bone marrow function for apheresis and lymphodepleting chemotherapy
  • Hemoglobin \>8 gm/dl (transfusions allowed)
  • Platelets \>50,000/uL (transfusions allowed)
  • Absolute Neutrophil Count (ANC) \> 500/uL
  • alanine aminotransferase (ALT)/aspartate aminotransferase (AST) \< 3 x institutional upper limit of normal (ULN) and Total bilirubin \< 1.5 mg/dl x institutional ULN, except with Gilbert's syndrome
  • Serum Creatinine \< 2 x the institutional ULN
  • Adequate cardiac function, defined as left ventricular ejection fraction (LVEF) \> 40% as assessed by echocardiogram or multiple uptake gated acquisition (MUGA) within 3 months of screening. Repeat testing may occur at Investigator's discretion.
  • Adequate vascular access for leukapheresis procedure (either peripheral line or surgically placed line).
  • Women of childbearing potential (defined as all women physiologically capable of becoming pregnant) must have a negative serum or urine pregnancy test AND agree to use highly effective methods of contraception for 1 year after the last dose of anti-CD19 CAR-T cells.
  • Males who have partners of childbearing potential must agree to use an effective barrier contraceptive method.
  • Ability to understand a written informed consent document, and the willingness to sign it.

Exclusion 20

  • Autologous transplant within 6 weeks of planned CAR-T cell infusion.
  • Recipient of prior CAR-T cell therapy targeting CD19 outside of this protocol.
  • Active other malignancy, other than non-melanoma skin cancer, carcinoma in situ (e.g., cervix, bladder, or breast).
  • Human immunodeficiency virus (HIV) seropositivity.
  • Serologic status reflecting active hepatitis B or C infection. Participants that are positive for hepatitis B core antibody, hepatitis B surface antigen (HBsAg), or hepatitis C antibody must have a negative polymerase chain reaction (PCR) prior to enrollment. (PCR positive participants will be excluded.)
  • Participants with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, pulmonary abnormalities or psychiatric illness/social situations that would limit compliance with study requirements.
  • Pregnant or breastfeeding women are excluded from this study because CAR-T cell therapy may be associated with the potential for teratogenic or abortifacient effects.
  • Because there is an unknown, but potential risk for adverse events in nursing infants secondary to treatment of the mother with CAR-T cells, breastfeeding should be discontinued.
  • These potential risks may also apply to other agents used in this study.
  • NOTE: Women of childbearing potential must have a negative serum or urine pregnancy test.
  • Participants with history of clinically relevant central nervous system (CNS) pathology such as epilepsy, seizure disorders, paresis, aphasia, uncontrolled cerebrovascular disease, severe brain injuries, dementia and Parkinson's disease.
  • History of autoimmune disease (e.g., rheumatoid arthritis, systemic lupus erythematosus) with requirement of immunosuppressive medication within 6 months.
  • Body weight \<40 kilograms(kg).
  • Eligibility for Infusion of Investigational Product:
  • Participants will undergo an evaluation of eligibility on day 1 prior to infusion of anti-CD19 CAR-T cell product. This eligibility criterion will include the inclusion and exclusion criteria required for enrollment with the following exceptions and additions:
  • No significant laboratory abnormalities. Laboratory result abnormalities that are considered not clinically significant by the principal investigator AND are not the result of a demonstrated active infection or an active central nervous system condition.
  • ECOG performance status \< 2
  • No evidence of uncontrolled intercurrent illness including, but not limited to ongoing or active infection, inflammatory response, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, pulmonary abnormalities or psychiatric illness/social situations.
  • No new neurologic symptoms suggestive of an active central nervous system condition, or uncontrolled CNS involvement by lymphoma.
  • No corticosteroid use within 7 days prior to infusion (with exception of agents used for prevention of emesis during lymphodepletive chemotherapy).

Where

1 site, 1 recruiting

University of California, San Francisco

San Francisco, California, United States

Recruiting

Contact

Potential match only. Final eligibility is determined by the study team.