Clinical Trials /

Study of Efficacy and Safety of CTL019 in Adult DLBCL Patients

NCT02445248

Description:

This is a multi-center, phase II study to determine the efficacy and safety of CTL019 in adult patients with relapsed or refractory DLBCL.

Related Conditions:
  • Diffuse Large B-Cell Lymphoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study of Efficacy and Safety of CTL019 in Adult DLBCL Patients
  • Official Title: A Phase II, Single Arm, Multicenter Trial to Determine the Efficacy and Safety of CTL019 in Adult Patients With Relapsed or Refractory Diffuse Large B-cell Lymphoma (DLBCL)

Clinical Trial IDs

  • ORG STUDY ID: CCTL019C2201
  • SECONDARY ID: 2014-003060-20
  • NCT ID: NCT02445248

Conditions

  • Diffuse Large B-cell Lymphoma (DLBCL)

Interventions

DrugSynonymsArms
CTL019CTL019

Purpose

This is a multi-center, phase II study to determine the efficacy and safety of CTL019 in adult patients with relapsed or refractory DLBCL.

Trial Arms

NameTypeDescriptionInterventions
CTL019ExperimentalSingle arm
  • CTL019

Eligibility Criteria

        Inclusion Criteria:

          -  Written informed consent must be obtained prior to any screening procedures

          -  Histologically confirmed DLBCL at last relapse(by central pathology review before
             enrolment.

             .- Relapsed or refractory disease after ≥2 lines of chemotherapy including rituximab
             and anthracycline and either having failed autologous Hematopoietic stem cell
             transplantation (ASCT), or being ineligible for or not consenting to ASCT

          -  Measurable disease at time of enrollment

          -  Life expectancy ≥12 weeks

          -  Eastern Cooperative Oncology Group (ECOG) performance status that is either 0 or 1 at
             screening

          -  Adequate organ function:

               -  Renal function defined as:

                    -  A serum creatinine of ≤1.5 x Upper Limit of Normal ULN OR

                    -  Estimated Glomerular Filtration Rate (eGFR) ≥ 60 mL/min/1.73 m2

               -  Liver function defined as:

                    -  Alanine Aminotransferase (ALT) ≤ 5 times the Upper Limit of Normal (ULN) for
                       age

                    -  Bilirubin ≤ 2.0 mg/dl with the exception of patients with
                       Gilbert-Meulengracht syndrome; patients with Gilbert-Meulengracht syndrome
                       may be included if their total bilirubin is ≤ 3.0 x ULN and direct bilirubin
                       ≤ 1.5 x ULN

               -  Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and
                  pulse oxygenation > 91% on room air

               -  Hemodynamically stable and Left Ventricle Ejection Fraction (LVEF) ≥ 45%
                  confirmed by echocardiogram or Multigated Radionuclide Angiography (MUGA)

               -  Adequate bone marrow reserve without transfusions defined as:

                    -  Absolute neutrophil count (ANC) > 1.000/mm3

                    -  Absolute lymphocyte count (ALC) ≥ 300/mm3

                    -  Platelets ≥ 50.000//mm3

                    -  Hemoglobin > 8.0 g/dl

               -  Must have an apheresis product of non-mobilized cells accepted for manufacturing

               -  Women of child-bearing potential (defined as all women physiologically capable of
                  becoming pregnant) and all male participants must agree to use highly effective
                  methods of contraception for at least 12 months following CTL019 infusion and
                  until CAR T cells are no longer present by PCR on two consecutive tests

        Exclusion Criteria:

          -  Prior treatment with any prior anti-CD19/anti-CD3 therapy, or any other anti-CD19
             therapy

          -  Treatment with any prior gene therapy product

          -  Active Central Nervous System (CNS) involvement by malignancy

          -  Prior allogeneic HSCT

          -  Eligible for and consenting to ASCT

          -  Chemotherapy other than lymphodepleting chemotherapy within 2 weeks of infusion

          -  Investigational medicinal product within the last 30 days prior to screening

          -  The following medications are excluded:

               -  Steroids: Therapeutic doses of steroids must be stopped > 72 hours prior to
                  CTL019 infusion. However, the following physiological replacement doses of
                  steroids are allowed: < 6 - 12 mg/m2/day hydrocortisone or equivalent

               -  Immunosuppression: Any immunosuppressive medication must be stopped ≥ 4 weeks
                  prior to enrollment

               -  Antiproliferative therapies other than lymphodepleting chemotherapy within two
                  weeks of infusion

               -  Antibody use including anti-CD20 therapy within 4 weeks prior to infusion or 5
                  half-lives of the respected antibody, whichever is longer

               -  CNS disease prophylaxis must be stopped > 1 week prior to CTL019 infusion (e.g.
                  intrathecal methotrexate)

          -  Prior radiation therapy within 2 weeks of infusion

          -  Active replication of or prior infection with hepatitis B or active hepatitis C( HCV
             RNA positive )

          -  HIV positive patients

          -  Uncontrolled acute life threatening bacterial, viral or fungal infection (e.g. blood
             culture positive ≤ 72 hours prior to infusion)

          -  Unstable angina and/or myocardial infarction within 6 months prior to screening

          -  Previous or concurrent malignancy with the following exceptions:

               -  Adequately treated basal cell or squamous cell carcinoma (adequate wound healing
                  is required prior to study entry)

               -  In situ carcinoma of the cervix or breast, treated curatively and without
                  evidence of recurrence for at least 3 years prior to the study

               -  A primary malignancy which has been completely resected and in complete remission
                  for ≥ 5 years

          -  Investigational medicinal product within the last 30 days prior to screening

          -  Pregnant or nursing (lactating) women

          -  Intolerance to the excipients of the CTL019 cell product

          -  Cardiac arrhythmia not controlled with medical management

          -  Patients on oral anticoagulation therapy

          -  Prior treatment with any adoptive T cell therapy

          -  Patients with active neurological auto immune or inflammatory disorders(e.g. Guillain
             Barre Syndrome, Amyptrophic Lateral Sclerosis)

        Other protocol-related inclusion/exclusion may apply.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall Response Rate (ORR)
Time Frame:5 years
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Incidence and severity of adverse events (AEs)
Time Frame:5 years
Safety Issue:
Description:
Measure:Time to response (TTR)
Time Frame:5 years
Safety Issue:
Description:
Measure:Duration of overall response (DOR)
Time Frame:5 years
Safety Issue:
Description:
Measure:Event free survival (EFS)
Time Frame:5 years
Safety Issue:
Description:
Measure:Progression free survival (PFS)
Time Frame:5 years
Safety Issue:
Description:
Measure:Overall survival (OS)
Time Frame:5 years
Safety Issue:
Description:
Measure:In vivo cellular Pharmacokinetic (PK) profile of CTL019 transduced cells into target tissues
Time Frame:5 years
Safety Issue:
Description:
Measure:Incidence of immunogenicity to CTL019
Time Frame:5 years
Safety Issue:
Description:
Measure:Number of Participants with presence of exposure to replication-competent lentivirus (RCL) as Assessed by quantitative polymerase chain reaction (qPCR)
Time Frame:5 years
Safety Issue:
Description:
Measure:Prevalence of immunogenicity to CTL019
Time Frame:5 years
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Novartis Pharmaceuticals

Trial Keywords

  • Diffuse large B-cell lymphoma,
  • DLBCL,
  • Relapsed/refractory,
  • CTL019
  • CART19
  • CART
  • CAR T cells
  • Chimeric antigen receptor

Last Updated

December 5, 2019