DK-CLIC-1901 CAR T-cells for treatment of patients with relapsed/refractory CD19 positive hematological malignancies (DAN-CART 1901)

Prior treatment

• Patients with concomitant genetic syndrome, such as Fanconi anemia, Kostmann syndrome, Shwachman syndrome or any other known familial bone marrow failure syndrome
• Prior treatment with any gene therapy product
• Treatment with any investigational agent within 30 days prior to enrollment
• Acute or chronic graft-versus-host disease with the need for systemic corticosteroid treatment within 4 weeks prior to enrollment

Other illness

• Prior malignancy (except for non-melanoma skin cancer) with on-going evidence of active disease or expected 5-year survival below 50% (as best estimation by treating oncologist)
• Active Central Nervous System (CNS) involvement by malignancy, defined by CNS-3 per NCCN guidelines for ALL, or any evidence of lymphoma on lumbar puncture or brain imaging (if performed).
• Pre-existing significant central neurological disorder defined as CTCAE grade 3-4 (other than CNS involvement of underlying hematological malignancy)
• History of anaphylaxis to gentamicin or its derivates
• Acute or chronic infections with HIV
• Active infection with, hepatitis B or hepatitis C
• Active severe bacterial, viral or fungal infection

Lab values

• Treatment with allogeneic haematopoietic stem cell transplantation within 6 months or donor lymphocyte infusion within 6 weeks from CAR-T infusion

Other

• Pregnant or breastfeeding women

• Relapsed/refractory hematologic disease (in peripheral blood, bone marrow or lymph node biopsy by flow cytometry) defined as one of the following: a. CD19 expressing B-cell acute lymphoblastic leukemia (B-ALL) with one of the following: • First VHR relapse (very early relapse (<18 months from initial diagnosis of ALL or very high risk genetic features ((KMT2A-AFF1, E2A/TCF3-PBX1 rearrangements, hypodiploidy, TP53 alterations) • NCI HR and MRD ≥0.01% at end of consolidation according to the ALLTogether protocol • Second or greater bone marrow (BM) relapse. • Any relapse after allogeneic haematopoietic stem cell transplantation (HSCT). • Primary refractory, defined as not achieving complete remission (CR) after 2 cycles of standard chemotherapy regimen, or chemo refractory, defined as not achieving CR after 1 cycle of standard chemotherapy for relapsed leukemia. • Philadelphia chromosome-positive ALL intolerant of or with 2 failed lines of tyrosine kinase inhibitor (TKI) therapy or if TKI therapy is contraindicated. • Ineligible for allogeneic HSCT due to comorbidity, contraindications to conditioning regimen, lack of a suitable donor, prior HSCT, or declined allogeneic HSCT after documented detailed discussion of this treatment option with the given patient. b. Histologically confirmed B-cell non-Hodgkin’s lymphoma including diffuse large B-cell lymphoma (DLBCL), Burkitt lymphoma, High-grade B cell lymphoma with or without double hit, precursor B-cell lymphoblastic lymphoma (B-LBL), primary mediastinal large B-cell lymphoma, mantle cell lymphoma, Richter-transformed chronic lymphocytic lymphoma (CLL) or transformed follicular lymphoma with one of the following: • Second or greater relapse. • Relapse after autologous or allogeneic haematopoietic stem cell transplantation (HSCT). • Primary refractory, defined as not achieving at least partiel remission (PR) at time of end of treatment scanning or as defined in frontline protocol. b. Follicular lymphoma (FL) with both of the following: • ≥2 prior lines of therapy that included both an anti-CD20 antibody and an alkylating agent. • Histologically confirmed by a pathology review to have FL (grade 1, 2 or 3A), and no evidence of histologic transformation or FL grade 3B. c. Chronic lymphocytic lymphoma (CLL) and small lymphocytic lymphoma (SLL) with both of the following: • ≥2 prior lines of therapy that included Bruton tyrosine kinase inhibitors • No evidence of active CNS involvement.
• Age of 1-75 years
• Life expectancy ≥ 12 weeks after enrollment
• Adequate organ function defined as: a. Lansky (<16 years) or Karnofsky (>16 years) score > 50% b. FEV1 or DLCOc ≥ 40 % of expected and oxygen saturation > 90% without oxygen supply c. LVEF > 45% and no symptoms of ischemic heart disease d. Bilirubin < 2 x upper normal limit for age (except for patient diagnosed with Gilbert syndrome) e. ALT < 5 x upper normal limit for age f. EDTA clearance >40mL/min (adults) or >30% of normal limit for age (children)
• Signed statement of consent after receiving oral and written study information
• Agreement to utilize highly effective contraception methods from time of leukapheresis until a minimum of 12 months after CAR-T infusion for all female patients of childbearing potential and all male patients with a female partner of childbearing potential. Highly effective contraception is defined as: total abstinence, female sterilization (oophorectomy, total hysterectomy or tubal ligation), male sterilization or use of oral, injected or implanted hormonal methods of contraception or placement or an intrauterine system/device.