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Clinical Trial Detail

huJCAR014 CAR-T Cells in Treating Adult Patients With Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma or Acute Lymphoblastic Leukemia

Complete title: A Two-Stage Phase 1 Open-Label Study of huJCAR014, CD19-targeted Chimeric Antigen Receptor (CAR)-Modified T cells Bearing a Human Binding Domain, in Adult Patients with Relapsed or Refractory B-cell Non-Hodgkin Lymphoma and Acute Lymphocytic Leukemia

Research Study Number 9364
Principal Investigator Cameron Turtle, PhD, MBBS
Phase I

Research Study Description

This phase I trial studies the side effects of autologous human anti-CD19 chimeric antigen receptor (CAR)-4-1BB-CD3zeta-EGFRt-expressing CD4+/CD8+ T-lymphocytes (huJCAR014) in treating patients with relapsed or refractory B-cell non-Hodgkin lymphoma or acute lymphoblastic leukemia. huJCAR014 CAR-T cells are made in the laboratory by genetically modifying a patient's T cells and may specifically kill cancer cells that have a molecule CD19 on their surfaces.

Eligibility Criteria (must meet the following to participate in this study)

Ages Eligible for Study: 18 Years and older (Adult, Senior)

Sexes Eligible for Study: All


- Ability to understand and provide informed consent

- Diagnosis of R/R B-cell NHL or ALL as defined below:

-- * Relapsed or refractory B-cell NHL meeting all of the following criteria:

--- ** Diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS); high grade B cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements; LBCL transformed from any indolent histology; or primary mediastinal B-cell lymphoma (PMBCL)

--- ** Prior treatment with an anthracycline and rituximab or another CD20-targeted agent (unless the disease is CD20-negative); transformed DLBCL (tDLBCL) must have failed treatment for DLBCL

--- ** At least one of the following:

---- *** Refractory disease after frontline chemo-immunotherapy

---- *** Not eligible for autologous hematopoietic stem cell transplant (auto-HSCT)

---- *** Relapsed or refractory disease after at least 2 lines of therapy or after auto-HSCT

---- *** Relapsed or refractory disease after allogeneic hematopoietic stem cell transplant (allo-HSCT)

-- * Relapsed or refractory B-cell ALL (patients with Burkitt's lymphoma/leukemia are not eligible)

-- * All B-ALL patients must have detectable disease by morphology, flow cytometry, cytogenetic analysis (e.g. polymerase chain reaction [PCR], fluorescence in situ hybridization [FISH], karyotyping) or imaging (positron emission tomography [PET]-computed tomography [CT])

--- ** Refractory: failure to achieve complete response (CR) (minimal residual disease [MRD]-negative) at the end of induction

--- ** Relapsed: recurrence of disease after achieving CR

- Evidence of CD19 expression by immunohistochemistry or flow cytometry on any prior or current tumor specimen or high likelihood of CD19 expression based on disease histology


- Screening evaluation appropriate for leukapheresis and T-cell collection

- Adequate vascular access for leukapheresis procedure (either peripheral line or surgically placed line)

- Documentation of CD19 expression on any prior or current tumor biopsy; patients who have received previous CD19-targeted therapy must have CD19-positive disease confirmed on a biopsy since completing the prior CD19-targeted therapy

- Internal review of histology


- Successful collection of T cells for huJCAR014 manufacturing

- For NHL, detectable PET-positive disease according to the "Recommendations for Initial Evaluation, Staging, and Response Assessment of Hodgkin and Non-Hodgkin Lymphoma: The Lugano Classification"

- Karnofsky performance status >= 60%

- Assessed by the investigator to have adequate bone marrow function to receive lymphodepleting conditioning chemotherapy

- Serum creatinine =< 1.5 x age-adjusted upper limit of normal (ULN) or calculated creatinine clearance (Cockcroft and Gault) > 30 mL/min/1.73 m^2

- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 5 x ULN and total bilirubin < 2.0 mg/dL unless due to malignancy or Gilbert's syndrome in the opinion of the PI or designee

- Common Terminology Criteria for Adverse Events (CTCAE) grade =< 1 dyspnea and oxygen saturation (SaO2) >= 92% on room air

- Left ventricular ejection fraction (LVEF) >= 40% as assessed by echocardiogram (ECHO) or multiple uptake gated acquisition (MUGA) scan performed within 1 month before starting lymphodepleting chemotherapy

- Women of childbearing potential (defined as all women physiologically capable of becoming pregnant) must agree to both of the following:

-- * Use highly effective methods of contraception for at least 6 months after the last dose of huJCAR014, and

-- * Have a negative serum pregnancy test performed within 28 days before starting lymphodepleting chemotherapy

- Males who have partners of childbearing potential must agree to use an effective barrier contraceptive method for at least 6 months after the last dose of huJCAR014

Other eligibility criteria may apply.

Exclusions (conditions that would prevent participation in this study)


- For patients in stage 1 only, prior treatment with any CD19 CAR T-cell therapy is excluded

- Known active hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) infection

- Pregnant or breastfeeding women

- Any known contraindication to leukapheresis

- Any known and irreversible contraindication to huJCAR014 therapy

- Medical, psychological, familial, sociological, or geographical condition that does not permit compliance with the protocol as judged by the PI or designee, or unwillingness or inability to follow protocol procedures


- History or presence of clinically relevant central nervous system (CNS) pathology that, in the opinion of the PI or designee, is a contraindication to lymphodepleting chemotherapy or huJCAR014 infusion

- History of another primary malignancy that has not been in remission for at least 2 years with the following exceptions: nonmelanoma skin cancer, curatively treated localized prostate cancer, cervical carcinoma in situ on biopsy or a squamous intraepithelial lesion on pap smear, or other malignancy considered by the investigator to have a low risk of relapse or progression

- Active autoimmune disease requiring immunosuppressive therapy, unless considered by the PI or designee to be eligible

- Presence of active acute or chronic graft versus host disease (GVHD)

- Use of any of the following:

-- * Cytotoxic or lymphotoxic agents (including prednisone > 5 mg/day or equivalent corticosteroid) within 1 week prior to leukapheresis; physiologic corticosteroid replacement, and topical or inhaled corticosteroids are not excluded

-- * GVHD therapies within 4 weeks prior to leukapheresis (e.g., calcineurin inhibitors, methotrexate or other chemotherapeutics, mycophenolate, rapamycin, thalidomide, immunosuppressive antibodies such as anti-TNF, anti-IL-6, or anti-IL-6R)

-- * Experimental agents within 4 weeks prior to leukapheresis unless progression is documented on therapy and at least 3 half-lives have elapsed prior to leukapheresis

-- * Radiation within 6 weeks prior to leukapheresis unless there is progressive disease in irradiated lesions or there are additional non-irradiated, positron emission tomography (PET)-positive lesions

-- * Allo-HSCT within 60 days prior to leukapheresis or donor lymphocyte infusion (DLI) within 6 weeks prior to leukapheresis

-- * Treatment with cladribine within 3 months prior to leukapheresis

-- * Treatment with alemtuzumab within 3 months prior to leukapheresis


- Uncontrolled and serious infection

- Presence of active acute or chronic GVHD

- DLI within 6 weeks prior to lymphodepletion chemotherapy

Other exclusion criteria may apply.

Research Study Number 9364
Contact Seattle Cancer Care Alliance Intake Office
Telephone 800-804-8824 / 206-606-1024

Keywords: Hematologic Malignancies; Leukemia; Lymphoma; Lymphoproliferative Disorders; Lymphoma, Non-Hodgkin (NHL); Neoplasms; Leukemia, Lymphoid; Immunoproliferative Disorders; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Immune System Diseases

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  • Talk to your health care providers first before making decisions about your health care.
  • Whether you are eligible for a research study depends on many things. There are specific requirements to be in research studies. These requirements are different for each study.

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