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

Prior treatment

• For patients in stage 1 only, prior treatment with any CD19 CAR T-cell therapy is excluded
• Any known and irreversible contraindication to huJCAR014 therapy
• 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
• DLI within 6 weeks prior to lymphodepletion chemotherapy

Other illness

• Known active hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) infection
• 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 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)
• Uncontrolled and serious infection

Lab values

• 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 encompassing all sites of known tumor within 6 weeks prior to leukapheresis, unless there is evidence of active disease after radiation by imaging, biopsy or clinical evaluation
  • 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

Other

• Pregnant or breastfeeding women
• Any known contraindication to leukapheresis
• Presence of active acute or chronic GVHD

• Male or female >= 18 years of age at the time of screening 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 (e.g. positron emission tomography [PET]/computed tomography [CT]) or a high likelihood of active disease
  • 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 available or planned 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
• Stage 2; cohort 2B (CAR-exposed) only:
  • Relapsed disease after achieving CR at the discretion of the principal investigator (PI) or designee, after prior CD19-targeted non-huJCAR014 CAR T-cell therapy. Patients who were in CR prior to the CD19-targeted non-huJCAR014 CAR T-cell therapy may be considered eligible at the discretion of the PI or designee. OR
  • Persistent disease after achieving PR at the discretion of the PI or designee, after prior CD19-targeted non-huJCAR014 CAR T-cell therapy. Patients who are less than 3 months from prior CD19-targeted non-huJCAR014 CAR T-cell therapy must have persistent disease on biopsy or imaging (e.g. PET-CT or CT) evidence of disease progression
• Successful collection of T cells for huJCAR014 manufacturing
• Detectable disease by imaging (for example PET +/- CT, magnetic resonance imaging [MRI]) and/or pathology evaluation
• 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