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出境医 / 临床实验 / CTA101 in the Treatment of Relapsed or Refractory Diffuse Large B-cell Lymphoma

CTA101 in the Treatment of Relapsed or Refractory Diffuse Large B-cell Lymphoma

Study Description
Brief Summary:
This is a single-center, non-randomized and dose-escalation study to evaluate the safety and efficacy of CTA101 in relapsed or refractory diffuse large B-cell lymphoma patients.

Condition or disease Intervention/treatment Phase
Diffuse Large B-cell Lymphoma Biological: CTA101 Phase 1

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 9 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Clinical Trial of CTA101 UCART Cells Injection in the Treatment of Relapsed or Refractory Diffuse Large B-cell Lymphoma
Estimated Study Start Date : December 1, 2019
Estimated Primary Completion Date : August 31, 2022
Estimated Study Completion Date : December 31, 2022
Arms and Interventions
Arm Intervention/treatment
Experimental: CTA101 Biological: CTA101
Universal CD19-directed CAR-T cells by a single infusion intravenously will be given in escalating doses. Subjects will been distributed into low dose (0.2×10^6), medium dose (2×10^6), and high dose (3×10^6).
Outcome Measures
Primary Outcome Measures :
  1. Dose-limiting toxicity（DLT） [ Time Frame: Baseline up to 35 days after T cell infusion ]
    Adverse events assessed according to NCI-CTCAE v4.03 criteria


Secondary Outcome Measures :
  1. Overall response rate (ORR) [ Time Frame: 4 weeks, 12 weeks, 6 months, 12 months, 18 months and 24 months ]
    Assessment of overall response rate for weeks 4, 12, months 6, 12, 18 and 24 in accordance with Lugano 2014 (overall response rate，OR)

  2. Disease control rate (DCR) [ Time Frame: 12 weeks, 6 months, 12 months, 18 months and 24 months ]
    Assessment of overall response rate for weeks 12, months 6, 12, 18 and 24 in accordance with Lugano 2014（disease control rate，DCR)


Eligibility Criteria
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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Histologically confirmed diagnosis of DLBCL per WHO Classification Criteria for Lymphocytic Tumors 2016, including DLBCL and PMBCL transformed from follicular lymphoma;

  2. Relapsed or refractory DLBCL (meeting one of the following conditions):

    1. Recurrence, progression or stable disease (SD) after treatment with second-line or above second-line chemotherapy regimens;
    2. Recurrence or progression after autologous hematopoietic stem cell transplantation;
  3. At least one measurable lesion must be ≥ 1.5cm in the longest diameter;
  4. Male or female aged 18-70 years;
  5. Estimated survival time ≥ 12 weeks;
  6. Serum albumin ≥ 30g/L, total bilirubin ≤ 25.7umol/L, creatinine ≤ 132.6umol/L, alanine transaminase (ALT) and aspartate aminotransferase (AST) <3 times of upper limit of normal;
  7. Absolute neutrophil count ≥ 1.0*10^9/L, platelet count ≥ 50*10^9/L;
  8. ECOG performance status 0 to 1;
  9. Echocardiographic diagnosis shows left ventricular ejection fraction (LVEF) ≥ 50%;
  10. No active infection in the lungs;
  11. Latest treatment (radiotherapy, chemotherapy, monoclonal antibody therapy or other treatment) must have been completed at least 2 weeks prior to screening;
  12. All women of child-bearing potential must have a negative blood or urine pregnancy test at screening, and agree to take medically acceptable contraception measures while on study treatment;
  13. Patients or their legal guardians volunteer to participate in the study and sign the informed consent.

Exclusion Criteria:

  1. History of hypersensitivity to any component of cell product;
  2. Prior treatment with any CAR T cell product or other genetically-modified T cell therapies;
  3. Recurrence after allogeneic hematopoietic stem cell transplantation;
  4. Patients with severe active infections (excluding simple urinary tract infection and bacterial pharyngitis), or currently receiving antibiotic therapy by intravenous drip. However, prophylactic antibiotic, antiviral and antifungal treatments are allowed;
  5. HBV DNA copy number detected by PCR in patients with active hepatitis B is > 1000 at screening (if HBsAg positive, routine antiviral therapy is required after enrollment), as well as CMV, hepatitis C, syphilis and HIV infection;
  6. Patients with New York Heart Associate (NYHA) Class III/IV cardiac insufficiency (see Appendix 1);
  7. Patients with Corrected QT interval(QTc)>450 msecs (Fridericia formula);
  8. Patients with a history of epilepsy;
  9. Intracranial extranodal lesions (tumor cells in cerebrospinal fluid, and/or MRI shows intracranial lymphoma invasion);
  10. Extensive invasions of gastrointestinal lymphoma (lesions involving the muscular layer, serosa and subserosa, excluding lesions confined to the mucosa and submucosa);

  11. History of other primary cancer, except for the following conditions:

    1. Cured non-melanoma after resection, such as basal cell carcinoma of the skin
    2. Cured carcinoma in situ, such as cervical cancer, bladder cancer or breast cancer
  12. Patients with autoimmune diseases requiring treatment, patients with immunodeficiency or requiring immunosuppressive therapy;
  13. Concurrent therapy with systemic steroids within 1 week prior to screening, except for the patients recently or currently receiving inhaled steroids;
  14. Women pregnant or lactating, with a pregnancy plan within 6 months, fertile but unable to take medically acceptable contraception measures;
  15. Patients who have participated in any other clinical studies within 2 weeks prior to screening;
  16. Any situations that the investigator believes may increase the risk of patients or interfere with the results of study.
Contacts and Locations

Contacts
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Contact: Jianyong Li, Ph.D. 025-83718836 lijianyonglm@126.com

Locations
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China, Jiangsu
the First Affiliated Hospital of Nanjing Medical University
Nanjing, Jiangsu, China, 210000
Sponsors and Collaborators
The First Affiliated Hospital with Nanjing Medical University
Nanjing Bioheng Biotech Co., Ltd.
Tracking Information
First Submitted Date  ICMJE July 17, 2019
First Posted Date  ICMJE July 19, 2019
Last Update Posted Date October 31, 2019
Estimated Study Start Date  ICMJE December 1, 2019
Estimated Primary Completion Date August 31, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 17, 2019) 		Dose-limiting toxicity（DLT） [ Time Frame: Baseline up to 35 days after T cell infusion ]
Adverse events assessed according to NCI-CTCAE v4.03 criteria
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 17, 2019)
  • Overall response rate (ORR) [ Time Frame: 4 weeks, 12 weeks, 6 months, 12 months, 18 months and 24 months ]
    Assessment of overall response rate for weeks 4, 12, months 6, 12, 18 and 24 in accordance with Lugano 2014 (overall response rate，OR)
  • Disease control rate (DCR) [ Time Frame: 12 weeks, 6 months, 12 months, 18 months and 24 months ]
    Assessment of overall response rate for weeks 12, months 6, 12, 18 and 24 in accordance with Lugano 2014（disease control rate，DCR)
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE CTA101 in the Treatment of Relapsed or Refractory Diffuse Large B-cell Lymphoma
Official Title  ICMJE A Phase I Clinical Trial of CTA101 UCART Cells Injection in the Treatment of Relapsed or Refractory Diffuse Large B-cell Lymphoma
Brief Summary This is a single-center, non-randomized and dose-escalation study to evaluate the safety and efficacy of CTA101 in relapsed or refractory diffuse large B-cell lymphoma patients.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Diffuse Large B-cell Lymphoma
Intervention  ICMJE Biological: CTA101
Universal CD19-directed CAR-T cells by a single infusion intravenously will be given in escalating doses. Subjects will been distributed into low dose (0.2×10^6), medium dose (2×10^6), and high dose (3×10^6).
Study Arms  ICMJE Experimental: CTA101
Intervention: Biological: CTA101
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: July 17, 2019) 		9
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 31, 2022
Estimated Primary Completion Date August 31, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Histologically confirmed diagnosis of DLBCL per WHO Classification Criteria for Lymphocytic Tumors 2016, including DLBCL and PMBCL transformed from follicular lymphoma;

  2. Relapsed or refractory DLBCL (meeting one of the following conditions):

    1. Recurrence, progression or stable disease (SD) after treatment with second-line or above second-line chemotherapy regimens;
    2. Recurrence or progression after autologous hematopoietic stem cell transplantation;
  3. At least one measurable lesion must be ≥ 1.5cm in the longest diameter;
  4. Male or female aged 18-70 years;
  5. Estimated survival time ≥ 12 weeks;
  6. Serum albumin ≥ 30g/L, total bilirubin ≤ 25.7umol/L, creatinine ≤ 132.6umol/L, alanine transaminase (ALT) and aspartate aminotransferase (AST) <3 times of upper limit of normal;
  7. Absolute neutrophil count ≥ 1.0*10^9/L, platelet count ≥ 50*10^9/L;
  8. ECOG performance status 0 to 1;
  9. Echocardiographic diagnosis shows left ventricular ejection fraction (LVEF) ≥ 50%;
  10. No active infection in the lungs;
  11. Latest treatment (radiotherapy, chemotherapy, monoclonal antibody therapy or other treatment) must have been completed at least 2 weeks prior to screening;
  12. All women of child-bearing potential must have a negative blood or urine pregnancy test at screening, and agree to take medically acceptable contraception measures while on study treatment;
  13. Patients or their legal guardians volunteer to participate in the study and sign the informed consent.

Exclusion Criteria:

  1. History of hypersensitivity to any component of cell product;
  2. Prior treatment with any CAR T cell product or other genetically-modified T cell therapies;
  3. Recurrence after allogeneic hematopoietic stem cell transplantation;
  4. Patients with severe active infections (excluding simple urinary tract infection and bacterial pharyngitis), or currently receiving antibiotic therapy by intravenous drip. However, prophylactic antibiotic, antiviral and antifungal treatments are allowed;
  5. HBV DNA copy number detected by PCR in patients with active hepatitis B is > 1000 at screening (if HBsAg positive, routine antiviral therapy is required after enrollment), as well as CMV, hepatitis C, syphilis and HIV infection;
  6. Patients with New York Heart Associate (NYHA) Class III/IV cardiac insufficiency (see Appendix 1);
  7. Patients with Corrected QT interval(QTc)>450 msecs (Fridericia formula);
  8. Patients with a history of epilepsy;
  9. Intracranial extranodal lesions (tumor cells in cerebrospinal fluid, and/or MRI shows intracranial lymphoma invasion);
  10. Extensive invasions of gastrointestinal lymphoma (lesions involving the muscular layer, serosa and subserosa, excluding lesions confined to the mucosa and submucosa);

  11. History of other primary cancer, except for the following conditions:

    1. Cured non-melanoma after resection, such as basal cell carcinoma of the skin
    2. Cured carcinoma in situ, such as cervical cancer, bladder cancer or breast cancer
  12. Patients with autoimmune diseases requiring treatment, patients with immunodeficiency or requiring immunosuppressive therapy;
  13. Concurrent therapy with systemic steroids within 1 week prior to screening, except for the patients recently or currently receiving inhaled steroids;
  14. Women pregnant or lactating, with a pregnancy plan within 6 months, fertile but unable to take medically acceptable contraception measures;
  15. Patients who have participated in any other clinical studies within 2 weeks prior to screening;
  16. Any situations that the investigator believes may increase the risk of patients or interfere with the results of study.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE
Contact: Jianyong Li, Ph.D. 025-83718836 lijianyonglm@126.com
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04026100
Other Study ID Numbers  ICMJE JSPH-CTA101
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party The First Affiliated Hospital with Nanjing Medical University
Study Sponsor  ICMJE The First Affiliated Hospital with Nanjing Medical University
Collaborators  ICMJE Nanjing Bioheng Biotech Co., Ltd.
Investigators  ICMJE Not Provided
PRS Account The First Affiliated Hospital with Nanjing Medical University
Verification Date October 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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