Clinical Trials /

CD79b CAR-T Cell Therapy for Patients With Relapsed and/or Refractory Acute Lymphoblastic Leukemia and B-cell Non-Hodgkin's Lymphoma

NCT04609241

Description:

A study of CD79b CAR-T Cell Therapy for Patients With Relapsed and/or Refractory Acute Lymphoblastic Leukemia and B-cell Non-Hodgkin's Lymphoma

Related Conditions:
  • Acute Myeloid Leukemia
  • B-Cell Acute Lymphoblastic Leukemia
  • B-Cell Non-Hodgkin Lymphoma
Recruiting Status:

Not yet recruiting

Phase:

Early Phase 1

Trial Eligibility

Document

Title

  • Brief Title: CD79b CAR-T Cell Therapy for Patients With Relapsed and/or Refractory Acute Lymphoblastic Leukemia and B-cell Non-Hodgkin's Lymphoma
  • Official Title: Clinical Trial for the Safety and Efficacy of Murine CD79b CAR-T Therapy for Patients With Relapsed and/or Refractory B-cell Acute Lymphoblastic Leukemia and B-cell Non-Hodgkin's Lymphoma

Clinical Trial IDs

  • ORG STUDY ID: CD79b-001
  • NCT ID: NCT04609241

Conditions

  • Relapsed and/or Refractory Acute Lymphoblastic Leukemia
  • Relapsed and/or Refractory B-cell Non-Hodgkin's Lymphoma

Interventions

DrugSynonymsArms
CD79b CAR-T CellsAdministration of CD79b CAR-T Cell

Purpose

A study of CD79b CAR-T Cell Therapy for Patients With Relapsed and/or Refractory Acute Lymphoblastic Leukemia and B-cell Non-Hodgkin's Lymphoma

Detailed Description

      This is a single arm, open-label, single-center study. This study is indicated for relapsed
      or refractory Relapsed and/or Refractory Acute Lymphoblastic Leukemia and B-cell
      Non-Hodgkin's Lymphoma. The selections of dose levels and the number of subjects are based on
      clinical trials of similar foreign products. 72 patients will be enrolled. Primary objective
      is to explore the safety, main consideration is dose-related safety.
    

Trial Arms

NameTypeDescriptionInterventions
Administration of CD79b CAR-T CellExperimental
  • CD79b CAR-T Cells

Eligibility Criteria

        Inclusion Criteria:

          -  Only For B-ALL

               1. No gender or age limit

               2. Histologically confirmed diagnosis of CD69b+ B-ALL per the US National
                  Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines for Acute
                  Myeloid Leukemia (2016.v1);

               3. Relapsed or refractory CD123+ AML (meeting one of the following conditions):

                    1. CR not achieved after standardized chemotherapy;

                    2. CR achieved following the first induction, but CR duration is less than 12
                       months;

                    3. Ineffectively after first or multiple remedial treatments;

                    4. 2 or more relapses;

               4. The number of primordial cells in bone marrow is > 5% (by morphology), and/or >
                  0.01% (by flowcytometry);

               5. Philadelphia chromosome negative(Ph-) subjects; Ph+ subjects who cannot tolerate
                  tyrosine kinase inhibitor (TKI) treatment or who do not respond to two kinds of
                  TKI treatment;

          -  Only For B-NHL

               1. No gender or age limit;

               2. Histologically confirmed diagnosis of DLBCL (NOS), FL, DLBCL transformed from
                  CLL/SLL, PMBCL, and HGBCL per the WHO Classification Criteria for Lymphoma
                  (2016);

               3. Relapsed or refractory B-NHL (meeting one of the following conditions):

               1. No response or relapse after second-line or above chemotherapy regimens;

               2. Primary drug resistance;

               3. Relapse after auto-HSCT;

               4. At least one assessable tumor lesion per Lugano 2014 criteria

          -  For both B-ALL and B-NHL

               1. Total bilirubin ≤ 51 umol/L, ALT and AST ≤ 3 times of upper limit ofnormal,
                  creatinine ≤ 176.8 umol/L;

               2. Echocardiogram shows left ventricular ejection fraction (LVEF) ≥50%;

               3. No active infection in the lungs, blood oxygen saturation in indoorair is ≥ 92%;

               4. Estimated survival time ≥ 3 months;

               5. ECOG performance status 0 to 2;

               6. Patients or their legal guardians volunteer to participate in the studyand sign
                  the informed consent.

        Exclusion Criteria:

          -  1. History of craniocerebral trauma, conscious disturbance,epilepsy,cerebrovascular
             ischemia, and cerebrovascular, hemorrhagicdiseases; 2. Electrocardiogram shows
             prolonged QT interval, severe heart diseasessuch as severe arrhythmia in the past; 3.
             Pregnant (or lactating) women; 4. Patients with severe active infections (excluding
             simple urinarytractinfectionand bacterial pharyngitis); 5. Active infection of
             hepatitis B virus or hepatitis C virus; 6. Previously treated with any CAR-T cell
             product or other genetically modified T cell therapies; 7. Insufficient amplification
             capacity in response to CD3 / CD28 co-stimulus signal (<5 times) 8.
             Creatinine>2.5mg/dl, or ALT / AST > 3 times of normal amounts, or bilirubin>2.0 mg/dl;
             9. Other uncontrolled diseases that were not suitable for this trial; 10. Patients
             with HIV infection; 11. Any situations that the investigator believes may increase the
             risk ofpatients or interfere with the results of study.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:N/A
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Dose-limiting toxicity (DLT)
Time Frame:Baseline up to 28 days after CD79b targeted CAR T-cells infusion
Safety Issue:
Description:Adverse events assessed according to NCI-CTCAE v5.0 criteria

Secondary Outcome Measures

Measure:Acute Lymphoblastic Leukemia (ALL), Overall response rate (ORR)
Time Frame:At Month 1, 3, 6, 12, 18 and 24
Safety Issue:
Description:Assessment of ORR (ORR = CR + CRi) at Month 6, 12, 18 and 24
Measure:ALL, Overall survival(OS)
Time Frame:Up to 2 years after CD79b CAR-T cells infusion
Safety Issue:
Description:From the first infusion of CD79b CAR-T cells to death or the last visit
Measure:ALL, Event-free survival (EFS)
Time Frame:Up to 2 years after CD79b CAR-T cells infusion
Safety Issue:
Description:From the first infusion of CD79b CAR-T cells to the occurrence of any event, including death, relapse or generelapse, disease progression (any one occurs first), and the last visit
Measure:B-cell Non-Hodgkin's Lymphoma(B-NHL), Overall response rate (ORR)
Time Frame:At Month 1, 3, 6, 12, 18 and 24
Safety Issue:
Description:Assessment of ORR (ORR = CR + CRi) at Month 6, 12, 18 and 24
Measure:B-NHL, Overall survival(OS)
Time Frame:Up to 2 years after CD79b CAR-T cells infusion
Safety Issue:
Description:From the first infusion of CD79b CAR-T cells to death or the last visit
Measure:B-NHL, Event-free survival (EFS)
Time Frame:Up to 2 years after CD79b CAR-T cells infusion
Safety Issue:
Description:From the first infusion of CD79b CAR-T cells to the occurrence of any event, including death, relapse or generelapse, disease progression (any one occurs first), and the last visit
Measure:Quality of life(EORTC QLQ-C30) Core 30 (EORTC QLQ-C30)
Time Frame:At Baseline, Month 1, 3, 6, 9 and 12
Safety Issue:
Description:Assessment using European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) scale [For item1-28: max score: 112, min score: 28, higher scores mean a better outcome; for item 28-29: max score: 14, min score: 2, higher scores mean a worse outcome] to measure Quality of life at Baseline, Month 1, 3, 6, 9 and 12
Measure:Activities of Daily Living (ADL) score
Time Frame:At Baseline, Month 1, 3, 6, 9 and 12
Safety Issue:
Description:Assessment using Activities of Daily Living (ADL) scale (Barthel Index) [max score: 100, min score: 0, higher scores mean a better outcome] at Baseline, Month 1, 3, 6, 9 and 12
Measure:Instrumental Activities of Daily Living (IADL) score
Time Frame:At Baseline, Month 1, 3, 6, 9 and 12
Safety Issue:
Description:Assessment of Instrumental Activities of Daily Living (IADL) scale [max score: 56, min score: 14, higher scores mean a worse outcome] at Baseline, Month 1, 3, 6, 9 and 12
Measure:Hospital Anxiety and Depression Scale (HADS) score
Time Frame:At Baseline, Month 1, 3, 6, 9 and 12
Safety Issue:
Description:Assessment using Hospital Anxiety and Depression Scale (HADS) [max score: 42, min score: 0, higher scores mean a worse outcome] at Baseline, Month 1, 3, 6, 9 and 12

Details

Phase:Early Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Zhejiang University

Last Updated

October 23, 2020