Clinical Trials /

Axi-Cel as a 2nd Line Therapy in Patients With Relapsed/Refractory Aggressive B Lymphoma Ineligible to Autologous Stem Cell Transplantation

NCT04531046

Description:

This is a phase 2, open-label, multicenter study evaluating axicabtagene ciloleucel (axi-cel) as a 2nd line therapy in patients with Relapsed/Refractory aggressive B-NHL who are ineligible to receive Autologous Stem Cell Transplantation but eligible to receive CAR T-cell therapy.

Related Conditions:
  • Diffuse Large B-Cell Lymphoma
  • Grade 3b Follicular Lymphoma
  • High Grade B-Cell Lymphoma, Not Otherwise Specified
  • Primary Mediastinal B-Cell Lymphoma
  • Transformed Non-Hodgkin Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Axi-Cel as a 2nd Line Therapy in Patients With Relapsed/Refractory Aggressive B Lymphoma Ineligible to Autologous Stem Cell Transplantation
  • Official Title: Phase 2, Open-Label Study Evaluating Axi-Cel as a 2nd Line Therapy in Patients With Relapsed/Refractory Aggressive B-Non Hodgkin Lymphoma (B-NHL) Who Are Ineligible to Autologous Stem Cell Transplantation

Clinical Trial IDs

  • ORG STUDY ID: ALYCANTE
  • NCT ID: NCT04531046

Conditions

  • B-Cell Lymphoma Refractory
  • B-cell Lymphoma Recurrent

Interventions

DrugSynonymsArms
axicabtagene ciloleucelaxi-celaxicabtagene ciloleucel

Purpose

This is a phase 2, open-label, multicenter study evaluating axicabtagene ciloleucel (axi-cel) as a 2nd line therapy in patients with Relapsed/Refractory aggressive B-NHL who are ineligible to receive Autologous Stem Cell Transplantation but eligible to receive CAR T-cell therapy.

Detailed Description

      Axicabtagene ciloleucel (axi-cel) is a chimeric antigen receptor (CAR) T-cell therapy
      directed against CD19 which has been approved for the treatment of relapse/refractory diffuse
      large B-cell lymphoma DLBCL and primary mediastinal large B-cell lymphoma (PMBCL) after 2 or
      more lines of systemic therapy.

      But administrating CAR T-cells earlier in the therapeutic strategy may be beneficial to
      patients.

      Axi-cel will improve the outcome of patients with DLBCL who are refractory or relapse early
      (i.e. within 1 year from end of treatment) after first-line therapy and who are not eligible
      for Autologous Stem Cell Transplantation (ASCT).

      Transplant-ineligible patients will include those who are deemed ineligible for high-dose
      chemotherapy and Hematopoietic Stem Cell Transplantation (HSCT) due to age, comorbidity, or
      prior ASCT.

      The primary endpoint will be complete metabolic response (CMR) at 3 months after Axi-cel
      infusion.
    

Trial Arms

NameTypeDescriptionInterventions
axicabtagene ciloleucelExperimentalSingle infusion administered intravenously at a target dose of 2 x 10^6 anti-CD19 CAR T cells/kg
  • axicabtagene ciloleucel

Eligibility Criteria

        Inclusion Criteria:

          -  Patient who understands and speaks one of the country official languages and signed
             Informed Consent Form

          -  Histologically proven relapsed or refractory aggressive B-cell non-Hodgkin lymphoma
             (B-NHL) of the following histology at relapse: diffuse large B-cell lymphoma (DLBCL),
             high-grade B-cell lymphoma (HGBL), follicular lymphoma Grade 3B per World Health
             Organization (WHO) 2016 classification and Primary mediastinal Bcell lymphomas.
             Indolent B-NHL who transformed into aggressive B-NHL and were previously treated with
             Rituximab-Cyclophosphamide, Hydroxydaunomycin, Oncovin, and Prednisone (R-CHOP) are
             eligible.

          -  Tumoral tissue (at diagnosis or relapse) available for central pathology review,
             exploratory endpoints and ancillary studies

          -  Positron-emission tomography (PET)-positive disease

          -  Patients must have received adequate first-line therapy including at a minimum: an
             anti-CD20 monoclonal antibody (rituximab or obinutuzumab), and Cyclophosphamide,
             Hydroxydaunomycin, Oncovin, and Prednisone (CHOP) or CHOP-like chemotherapy

          -  Relapsed or refractory disease after first-line chemoimmunotherapy (full dose of
             R-CHOP or R-CHOP-like regimen), documented by PET-scan

          -  At least 2 weeks must have elapsed since any prior systemic cancer therapy at the time
             the patient provides consent

          -  Patients must be autologous stem cell transplantation (ASCT)-ineligible

          -  Patients must be CAR-T-eligible

          -  Females of childbearing potential must have a negative serum or urine pregnancy test
             (females who have undergone surgical sterilization or who have been postmenopausal for
             at least 12 months are not considered to be of childbearing potential)

        Exclusion Criteria:

          -  Patients who received more than one prior line of systemic therapy

          -  Patients who are intolerant to first-line therapy or who received suboptimal
             first-line therapy, including dose-reduced R-CHOP ("R-miniCHOP"), and those who
             discontinued prematurely first-line therapy due to toxicity are not eligible

          -  Prior CD19 targeted therapy

          -  Patients with cardiac atrial or cardiac ventricular lymphoma involvement

          -  Requirement for urgent therapy due to tumor mass effects, such as bowel obstruction or
             blood vessel compression

          -  Patient with clinically significant pleural effusion

          -  History of another primary malignancy that has not been in remission for at least 2
             years (except for nonmelanoma skin cancer or carcinoma in situ (eg, cervix, bladder,
             breast))

          -  Patients with detectable Central Nervous System (CNS) lymphoma

          -  History or presence of non-malignant CNS disorder, such as seizure disorder requiring
             anti-convulsive therapy, cerebellar disease, or any autoimmune disease with CNS
             involvement disease

          -  Active hepatitis B or hepatitis C infection, positive serology of human
             immunodeficiency virus (HIV) at the time of screening

          -  Uncontrolled systemic fungal, bacterial, viral or other infection despite appropriate
             antibiotics or other treatment at the time of leukapheresis or axi-cel administration

          -  History of any one of the following cardiovascular conditions within the past 6
             months: Class III or IV heart failure as defined by the New York Heart Association,
             cardiac angioplasty or stenting, myocardial infarction, unstable angina, or other
             clinically significant cardiac disease

          -  History of autoimmune disease requiring systemic immunosuppression and/or systemic
             disease modifying agents within the last year

          -  History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced
             pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis per chest
             computed tomography (CT) scan at screening.

          -  History of severe immediate hypersensitivity reaction to tocilizumab or any of the
             agents used in this study

          -  History of severe immediate hypersensitivity reaction attributed to aminoglycosides

          -  Treatment with a live, attenuated vaccine within 6 weeks prior to initiation of study
             treatment or anticipation of need for such a vaccine during the course of the study

          -  Women of childbearing potential who are pregnant or breastfeeding

          -  Adult person unable to provide informed consent because of intellectual impairment,
             any serious medical condition, laboratory abnormality or psychiatric illness
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Complete Metabolic Response (CMR) - determined by investigator
Time Frame:3 months from axi-cel infusion
Safety Issue:
Description:CMR from axi-cel infusion (without additional anticancer therapy) based on investigator disease assessment according to PET-scan (using the Lugano Response Criteria)

Secondary Outcome Measures

Measure:Complete Metabolic Response (CMR) - détermined by central imaging review
Time Frame:3 months from axi-cel infusion
Safety Issue:
Description:CMR from axi-cel infusion (without additional anticancer therapy) determined by central imaging review (using the Lugano Response Criteria)
Measure:Best objective response
Time Frame:between Day 14 and Month 12
Safety Issue:
Description:Percentage of CMR and Partial MR determined by investigator disease assessment
Measure:Number of Adverse Events (AE)
Time Frame:at 30 days after axi-cel infusion
Safety Issue:
Description:AEs of grade ≥ 2 (CTCAE - version 5.0) and all grades (ASBMT Consensus Grading) for Cytokine Release Syndrome and Neurologic Toxicity (Lee, 2019)

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:The Lymphoma Academic Research Organisation

Last Updated

August 25, 2020