CD45BE-HSPC + CART-45 Cells

Korábbi kezelés

• Prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen.
• Active acute or chronic GVHD requiring systemic therapy.
• Dependence on systemic steroids or immunosuppressant medications. For additional details regarding use of steroid and immunosuppressant medications.

Más betegség

• Active hepatitis B or hepatitis C infection
• Any active, uncontrolled infection.
• Class III/IV cardiovascular disability according to the New York Heart Association Classification.
• Clinically apparent arrhythmia or arrhythmias that are not stable on medical management within two weeks of physician-investigator confirmation of eligibility.
• Active CNS involvement. Patients with a history of CNS involvement that was successfully treated are eligible. A CNS evaluation is only required for eligibility if a subject is experiencing signs/symptoms of CNS involvement.
• Patients with evidence of a circulating T-cell malignancy as measured by flow cytometry.
• Active autoimmune disease requiring systemic immunosuppressive treatment equivalent to ≥ 10mg of prednisone. Patients with autoimmune neurologic diseases (such as MS) will be excluded.

Laborértékek

• History of allergy or hypersensitivity to study product excipients (human serum albumin, DMSO, and Dextran 40).

Egyéb

• Severe, active co-morbidity that, in the opinion of the physician-investigator, would preclude participation in this study.
• Pregnant or nursing (lactating) patients. Participants of reproductive potential must agree to use acceptable birth control methods.

• Signed informed consent form 2. Male or females age ≥ 18 years 3. Disease-Specific Criteria
• B-cell Non-Hodgkin Lymphoma (B-cell NHL)- including the following sub-types:
• Patients with any of the following large B-cell lymphoma diagnoses who meet the prior treatment criteria outlined below: Diffuse Large B-cell Lymphoma not otherwise specified (DLBCL NOS); Primary Cutaneous DLBCL; Primary Mediastinal (thymic) Large B-cell Lymphoma; ALK+ Anaplastic Large B-cell Lymphoma; High-Grade B-cell Lymphoma with MYC and BCL2 and/or BCL6 rearrangements (i.e., "Double or Triple Hit"); High-grade B-cell Lymphoma, NOS; T-cell Rich B-cell Lymphoma; Transformed Follicular Lymphoma; or any aggressive B-cell lymphoma arising from indolent lymphoma.
• Patients must have either failed/relapsed after, or be ineligible for, prior commercial CAR T cell therapy; AND 2. Relapsed/refractory disease after at least 2 prior lines of appropriate therapy.
• Follicular Lymphoma
• Patients must have either failed/relapsed after, or be ineligible for, prior commercial CAR T cell therapy; AND
• Relapsed/refractory disease after at least 2 prior lines of systemic therapy (not including a single agent monoclonal antibody therapy).
• Mantle Cell Lymphoma
• Patients must have either failed/relapsed after, or be ineligible for, prior commercial CAR T cell therapy; AND
• Relapsed/refractory disease after at least 2 prior lines of systemic therapy, including a Bruton tyrosine kinase (TKI) inhibitor. Single-agent monoclonal antibody therapy does not count towards prior lines of therapy.
  • Marginal Zone Lymphoma- relapsed/refractory disease after at least 2 prior lines of appropriate therapy, including a Bruton tyrosine kinase (TKI) inhibitor. Note: Single-agent monoclonal antibody therapy does not count towards prior lines of therapy.
  • T-cell Non-Hodgkin Lymphoma (T-cell NHL)
  • Histologically or cytologically confirmed relapsed or refractory (r/r) mature aggressive T- and NK-cell neoplasms as defined in the 5th edition of the WHO Classification of Hematolymphoid tumors, which includes any of the following diagnoses:
  • Peripheral T-cell Lymphoma, NOS (PTCL-NOS);
  • Nodal T-cell Lymphomas with T Follicular Helper [TFH] Phenotype, including Follicular T cell Lymphoma, Angioimmunoblastic Lymphoma, or Anaplastic Large Cell Lymphoma (ALCL);
  • ALK+ or ALK-, Enteropathy-Associated T-cell Lymphoma (EATL);
  • Monomorphic Epitheliotropic Intestinal T-cell Lymphoma (MEITL);
  • Extranodal NK/T-cell Lymphoma;
  • Primary Cutaneous T-cell Lymphoma (CTCL);
  • Transformed Mycosis Fungoides (tMF) without blood involvement;
  • Primary Cutaneous Aggressive Epidermotropic CD8+ Cytotoxic T-Cell Lymphoma;
  • Subcutaneous Panniculitis-like T-cell Lymphoma.
  • Must have received at least one prior line of systemic therapy for their lymphoma. Additional prior treatment provisions required for the following indications:
• Participants with Anaplastic Large Cell Lymphoma (ALCL) must have received prior Brentuximab vedotin, unless contraindicated.
• Participants with Subcutaneous Panniculitis-like T-cell Lymphoma or Transformed Mycosis Fungoides (tMF) must have received at least 2 prior lines of systemic therapy.
• Hodgkin Lymphoma (HL)
• Patients with histologically proven classical Hodgkin Lymphoma that is CD45 positive by IHC or flow cytometry by a CLIA certified laboratory; AND
• Relapsed/refractory disease after at least 2 prior lines of therapy which must include the following:
• Brentuximab vedotin and immune checkpoint inhibitors (unless contraindicated); AND
• Autologous stem cell transplant (unless patient has chemorefractory disease to salvage treatment) d. Large Cell Transformation of CLL (Richter's Transformation) i. Patients must be primary refractory or received at least 1 prior line of treatment for Richter's Transformation.
• Patients are appropriate candidates for autologous HSCT as per physician-investigator clinical discretion
• Patients with relapsed disease after prior allogeneic SCT must meet the following criteria:
• Have no active GVHD and require no immunosuppression
• Are more than 6 months from transplant at the time of physician-investigator confirmation of eligibility
• Adequate organ function defined as:
• Serum creatinine ≤ 1.5x ULN or estimated creatinine clearance ≥ 35 mL/min and not on dialysis
• ALT/AST ≤ 3 x ULN
• Direct bilirubin ≤ 2.0 mg/dl; for patients with Gilbert's syndrome direct bilirubin must be ≤ 3.0 mg/dl
• Left Ventricular Ejection Fraction (LVEF) ≥ 40% confirmed by ECHO/MUGA
• DLCO > 45% predicted value; adjusted for level of hemoglobin
• Must have minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and pulse oxygen > 92% on room air 7. ECOG Performance Status 0-1