Study of genetically modified patient immune cells in treatment of refractory leukemia and lymphoma of B-cell origi

Phase 1

• Conditions: Acute Lymphoblastic Leukemia and B-cell Non Hodgkin Lymphoma; MedDRA version: 21.1Level: LLTClassification code 10066109Term: Precursor B-lymphoblastic leukemia acuteSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.0Level: LLTClassification code 10012855Term: Diffuse large cell lymphoma (Diffuse large B-cell lymphoma) (Working Formulation)System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0Level: LLTClassification code 10060669Term: B-cell chronic lymphocytic leukemia/prolymphocytic leukemia/small lymphocytic lymphomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0Level: HLTClassification code 10036524Term: Precursor B-lymphoblastic lymphomasSystem Organ Class: 100000004851; MedDRA version: 20.0Level: HLTClassification code 10026798Term: Mantle cell lymphomasSystem Organ Class: 100000004851; MedDRA version: 20.0Level: HLTClassification code 10020068Term: High grade B-cell lymphomas Burkitt-like lymphomaSystem Organ Class: 100000004851; MedDRA version: 20.0Level: HLTClassification code 10036711Term: Primary mediastinal large B-cell lymphomasSystem Organ Class: 100000004851; MedDRA version: 24.0Level: PTClassification code 10085128Term: Follicular lymphomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2021-006556-14-DK
• Lead Sponsor: Rigshospitalet

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2022-04-11
• Last Update Posted: 19 August 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

1.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:
•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, 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 partiel remission (PR) at time of interim-scanning or as defined in frontline protocol.

2.Age of 1-70 years
3.Life expectancy = 12 weeks after enrollment
4.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)
5.Signed statement of consent after receiving oral and written study information
6.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.

Are the trial subjects under 18? yes
Number of subjects for this age range: 20
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 8
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 2

Exclusion Criteria

oPrior 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)
oPatients with concomitant genetic syndrome, such as Fanconi anemia, Kostmann syndrome, Shwachman syndrome or any other known familial bone marrow failure syndrome
oPrior treatment with any gene therapy product
oTreatment with any investigational agent within 30 days prior to enrollment
oTreatment with allogeneic haematopoietic stem cell transplantation within 6 months or donor lymphocyte infusion within 6 weeks from CAR-T infusion
oAcute or chronic graft-versus-host disease with the need for systemic corticosteroid treatment within 4 weeks prior to enrollment
oAcute or chronic infections with HIV
oActive infection with, hepatitis B or hepatitis C
oActive severe bacterial, viral or fungal infection
oActive 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).
oPre-existing significant central neurological disorder defined as CTCAE grade 3-4 (other than CNS involvement of underlying hematological malignancy)
oHistory of anaphylaxis to gentamicin or its derivates
oPregnant or breastfeeding women

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified