Safety and Efficacy of Axicabtagene Ciloleucel in Combination With Utomilumab in Adults With Refractory Large B-cell Lymphoma

NCT03704298

Last updated date
Study Location
Mayo Clinic
Rochester, Minnesota, 55905, United States
Contact
1-844-454-5483(1-844-454-KITE)

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1-844-454-5483(1-844-454-KITE)

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Eligibility Criteria
condition
The disease, disorder, syndrome, illness, or injury that is being studied.
Relapsed/Refractory Large B-cell Lymphoma
Sex
Females and Males
Age
Pediatric Trials: 0-17 Years
Adult Trials: 18+ Years
18 + years
Inclusion Criteria
The factors, or reasons, that allow a person to participate in a clinical study.
Show details

- Histologically proven large B-cell lymphoma including the following types:

- Diffuse large B cell lymphoma (DLBCL) not otherwise specified (ABC/GCB)

- High grade B-cell lymphoma (HGBCL) with or without MYC and BCL2 and/or BCL6 rearrangement

- DLBCL arising from follicular lymphoma

- T cell/histiocyte rich large B-cell lymphoma

- DLBCL associated with chronic inflammation

- Primary cutaneous DLBCL, leg type

- Epstein-Barr virus (EBV) + DLBCL

- Relapsed or chemotherapy-refractory disease, defined as one or more of the following:

- No response to first-line therapy (primary refractory disease); subjects who are intolerant to first-line systemic chemotherapy are excluded

- Progressive disease (PD) as best response to first-line therapy

- Stable disease (SD) as best response after at least 4 cycles of first-line therapy (eg, 4 cycles of R-CHOP) with SD duration no longer than 6 months from last dose of therapy

- No response to second or greater lines of therapy

- PD as best response to most recent therapy regimen

- SD as best response after at least 2 cycles of last line of therapy with SD duration no longer than 6 months from last dose of therapy OR

- Refractory post-autologous stem cell transplant (ASCT)

- Disease progression or relapsed . 12 months after ASCT (must have biopsy proven recurrence in relapsed participant)

- if salvage therapy is given post-ASCT, the participant must have had no response to or relapsed after the last line of therapy

- Relapsed or refractory LBCL including DLBCL, TFL, and HGBCL after 2 or more lines of systemic therapy that is defined by and aligns with currently approved indication:

- Relapsed disease after 2 or more lines of systemic therapy

- Best response that is less than a CR to second or greater line of systemic therapy

- At least 1 measureable lesion according to the Lugano Classification (Cheson et al, 2014). Lesions that have been previously irradiated will be considered measurable only if progression has been documented following completion of radiation therapy.

- Participant must have received adequate prior therapy including at a minimum:

- Anti-CD20 monoclonal antibody unless investigator determines that tumor is CD20-negative, and

- An anthracycline containing chemotherapy regimen

- No radiographic evidence, suspicion and/or history of central nervous system (CNS) involvement of lymphoma

- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

- Absolute neutrophil count (ANC) ≥ 1000/μL

- Platelet count ≥ 75,000/μL

- Absolute lymphocyte count ≥ 100/μL

- Adequate renal, hepatic, pulmonary, and cardiac function defined as:

- Creatinine clearance (as estimated by Cockcroft Gault) ≥ 60 mL/min

- Serum alanine aminotransferase/aspartate aminotransferase (ALT/AST) ≤ 2.5 upper limit of normal (ULN)

- Total bilirubin ≤ 1.5 mg/dL, except in individuals with Gilbert's syndrome.

- Cardiac ejection fraction ≥ 50% and no evidence of pericardial effusion within 180 days provided the subject did not receive an anthracycline-based treatment or experience a cardiac event or change in performance status

- No clinically significant pleural effusion

- Baseline oxygen saturation > 92% on room air

Key

Exclusion Criteria
The factors, or reasons, that prevent a person from participating in a clinical study.
Show details


- Histologically proven primary mediastinal B-cell lymphoma (PMBCL)


- History of Richter's transformation of chronic lymphocytic lymphoma (CLL)


- Prior chimeric antigen receptor therapy or other genetically modified T-cell therapy


- History of severe, immediate hypersensitivity reaction attributed to aminoglycosides


- History of HIV infection or acute or chronic active hepatitis B or C infection.
Individuals with history of hepatitis infection must have cleared their infection as
determined by standard serological and genetic testing per current Infectious Diseases
Society of America (IDSA) guidelines or applicable country guidelines


- Individuals with detectable cerebrospinal fluid malignant cells, brain metastases, or
a history of CNS lymphoma


- History or presence of CNS disorder, such as seizure disorder, cerebrovascular
ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS
involvement


- Individuals with cardiac atrial or cardiac ventricular lymphoma involvement


- History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or
other clinically significant cardiac disease within 12 months of enrollment


- Requirement for urgent therapy due to tumor mass effects (eg, blood vessel
compression, bowel obstruction, or transmural gastric involvement


- Primary immunodeficiency


- History of autoimmune disease (eg, Crohn's, rheumatoid arthritis, systemic lupus)
resulting in end organ injury or requiring systemic immunosuppression/systemic disease
modifying agents within the last 2 years. Patients with a history of
autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone and
patients with controlled type 1 diabetes mellitus on a stable insulin regimen may be
eligible for this study


- History of symptomatic deep vein thrombosis or pulmonary embolism within 6 months of
enrollment


- Any medical condition likely to interfere with assessment of safety or efficacy of
study treatment


- Autologous stem cell transplant within 6 weeks of planned enrollment


- Prior organ transplantation including prior allogeneic stem cell transplant (SCT)


- Use of any standard or experimental anti-cancer therapy within 2 weeks prior to
enrollment, including cytoreductive therapy and radiotherapy, immunotherapy, or
cytokine therapy (except for erythropoietin) Prior treatment with PD-L1 inhibitor,
PD-1 inhibitor, anti-CTLA4, anti-CD137 (4-1BB), anti-OX40 or other immune checkpoint
blockade or activator therapy


- History of idiopathic pulmonary fibrosis, organizing pneumonia (eg, bronchiolitis
obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active
pneumonitis per chest CT scan at screening. History of radiation pneumonitis in the
radiation field (fibrosis) is allowed


- In the investigator's judgment, the subject is unlikely to complete all
protocol-required study visits or procedures, including follow-up visits, or comply
with the study requirements for participation.


Note: Other protocol defined Inclusion/Exclusion criteria may apply.

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Relapsed/Refractory Large B-cell LymphomaSafety and Efficacy of Axicabtagene Ciloleucel in Combination With Utomilumab in Adults With Refractory Large B-cell Lymphoma
NCT03704298
  1. Rochester, Minnesota
  2. Palo Alto, California
  3. Santa Monica, California
  4. Tampa, Florida
  5. Boston, Massachusetts
  6. New York, New York
ALL GENDERS
18 Years+
years
MULTIPLE SITES
Advanced Information
Descriptive Information
Brief Title  ICMJE Safety and Efficacy of Axicabtagene Ciloleucel in Combination With Utomilumab in Adults With Refractory Large B-cell Lymphoma
Official Title  ICMJE A Phase 1/2 Multi-center Study Evaluating the Safety and Efficacy of Axicabtagene Ciloleucel in Combination With Utomilumab in Subjects With Relapsed/Refractory Large B-Cell Lymphoma
Brief Summary

The primary objectives of this study are:

Phase 1: To evaluate the safety of axicabtagene ciloleucel in combination with utomilumab and to identify the most appropriate dose and timing of utomilumab to carry forward into Phase 2

Phase 2: To evaluate the efficacy of axicabtagene ciloleucel and utomilumab in participants with refractory large B-cell lymphoma

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Relapsed/Refractory Large B-cell Lymphoma
Intervention  ICMJE
  • Drug: Cyclophosphamide
    Administered according to package insert
  • Drug: Fludarabine
    Administered according to package insert
  • Biological: Axicabtagene Ciloleucel
    A single infusion of chimeric antigen receptor (CAR)-transduced autologous T cells administered intravenously
    Other Name: Yescarta®
  • Biological: Utomilumab
    Administered as an IV infusion
Study Arms  ICMJE Experimental: Axicabtagene ciloleucel plus utomilumab

Phase 1: Participants will receive cyclophosphamide and fludarabine conditioning chemotherapy followed by axicabtagene ciloleucel treatment on Day 0 plus utomilumab on study Day 1 or study Day 21 and continuing once every 4 weeks (Q4W) for 6 months or until Progressive Disease, whichever comes first.

Phase 2: Participants will receive cyclophosphamide and fludarabine conditioning chemotherapy followed by axicabtagene ciloleucel and utomilumab based on the dose/regimen selected to move forward from the Phase 1 portion of the study as recommended by the internal Safety Review Team.

Interventions:
  • Drug: Cyclophosphamide
  • Drug: Fludarabine
  • Biological: Axicabtagene Ciloleucel
  • Biological: Utomilumab
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 Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 10, 2018)
48
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE February 2036
Estimated Primary Completion Date February 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Key Inclusion Criteria:

  • Histologically proven large B-cell lymphoma including the following types:

    • Diffuse large B cell lymphoma (DLBCL) not otherwise specified (ABC/GCB)
    • High grade B-cell lymphoma (HGBCL) with or without MYC and BCL2 and/or BCL6 rearrangement
    • DLBCL arising from follicular lymphoma
    • T cell/histiocyte rich large B-cell lymphoma
    • DLBCL associated with chronic inflammation
    • Primary cutaneous DLBCL, leg type
    • Epstein-Barr virus (EBV) + DLBCL
  • Relapsed or chemotherapy-refractory disease, defined as one or more of the following:

    • No response to first-line therapy (primary refractory disease); subjects who are intolerant to first-line systemic chemotherapy are excluded

      • Progressive disease (PD) as best response to first-line therapy
      • Stable disease (SD) as best response after at least 4 cycles of first-line therapy (eg, 4 cycles of R-CHOP) with SD duration no longer than 6 months from last dose of therapy
    • No response to second or greater lines of therapy

      • PD as best response to most recent therapy regimen
      • SD as best response after at least 2 cycles of last line of therapy with SD duration no longer than 6 months from last dose of therapy OR
    • Refractory post-autologous stem cell transplant (ASCT)

      • Disease progression or relapsed . 12 months after ASCT (must have biopsy proven recurrence in relapsed participant)
      • if salvage therapy is given post-ASCT, the participant must have had no response to or relapsed after the last line of therapy
    • Relapsed or refractory LBCL including DLBCL, TFL, and HGBCL after 2 or more lines of systemic therapy that is defined by and aligns with currently approved indication:

      • Relapsed disease after 2 or more lines of systemic therapy
      • Best response that is less than a CR to second or greater line of systemic therapy
  • At least 1 measureable lesion according to the Lugano Classification (Cheson et al, 2014). Lesions that have been previously irradiated will be considered measurable only if progression has been documented following completion of radiation therapy.
  • Participant must have received adequate prior therapy including at a minimum:

    • Anti-CD20 monoclonal antibody unless investigator determines that tumor is CD20-negative, and
    • An anthracycline containing chemotherapy regimen
  • No radiographic evidence, suspicion and/or history of central nervous system (CNS) involvement of lymphoma
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Absolute neutrophil count (ANC) ? 1000/?L
  • Platelet count ? 75,000/?L
  • Absolute lymphocyte count ? 100/?L
  • Adequate renal, hepatic, pulmonary, and cardiac function defined as:

    • Creatinine clearance (as estimated by Cockcroft Gault) ? 60 mL/min
    • Serum alanine aminotransferase/aspartate aminotransferase (ALT/AST) ? 2.5 upper limit of normal (ULN)
    • Total bilirubin ? 1.5 mg/dL, except in individuals with Gilbert's syndrome.
    • Cardiac ejection fraction ? 50% and no evidence of pericardial effusion within 180 days provided the subject did not receive an anthracycline-based treatment or experience a cardiac event or change in performance status
    • No clinically significant pleural effusion
    • Baseline oxygen saturation > 92% on room air

Key Exclusion Criteria:

  • Histologically proven primary mediastinal B-cell lymphoma (PMBCL)
  • History of Richter's transformation of chronic lymphocytic lymphoma (CLL)
  • Prior chimeric antigen receptor therapy or other genetically modified T-cell therapy
  • History of severe, immediate hypersensitivity reaction attributed to aminoglycosides
  • History of HIV infection or acute or chronic active hepatitis B or C infection. Individuals with history of hepatitis infection must have cleared their infection as determined by standard serological and genetic testing per current Infectious Diseases Society of America (IDSA) guidelines or applicable country guidelines
  • Individuals with detectable cerebrospinal fluid malignant cells, brain metastases, or a history of CNS lymphoma
  • History or presence of CNS disorder, such as seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement
  • Individuals with cardiac atrial or cardiac ventricular lymphoma involvement
  • History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant cardiac disease within 12 months of enrollment
  • Requirement for urgent therapy due to tumor mass effects (eg, blood vessel compression, bowel obstruction, or transmural gastric involvement
  • Primary immunodeficiency
  • History of autoimmune disease (eg, Crohn's, rheumatoid arthritis, systemic lupus) resulting in end organ injury or requiring systemic immunosuppression/systemic disease modifying agents within the last 2 years. Patients with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone and patients with controlled type 1 diabetes mellitus on a stable insulin regimen may be eligible for this study
  • History of symptomatic deep vein thrombosis or pulmonary embolism within 6 months of enrollment
  • Any medical condition likely to interfere with assessment of safety or efficacy of study treatment
  • Autologous stem cell transplant within 6 weeks of planned enrollment
  • Prior organ transplantation including prior allogeneic stem cell transplant (SCT)
  • Use of any standard or experimental anti-cancer therapy within 2 weeks prior to enrollment, including cytoreductive therapy and radiotherapy, immunotherapy, or cytokine therapy (except for erythropoietin) Prior treatment with PD-L1 inhibitor, PD-1 inhibitor, anti-CTLA4, anti-CD137 (4-1BB), anti-OX40 or other immune checkpoint blockade or activator therapy
  • History of idiopathic pulmonary fibrosis, organizing pneumonia (eg, bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis per chest CT scan at screening. History of radiation pneumonitis in the radiation field (fibrosis) is allowed
  • In the investigator's judgment, the subject is unlikely to complete all protocol-required study visits or procedures, including follow-up visits, or comply with the study requirements for participation.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Sex/Gender  ICMJE
Sexes Eligible for Study:All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Medical Information1-844-454-5483(1-844-454-KITE)[email protected]
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03704298
Other Study ID Numbers  ICMJE KTE-C19-111
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD:No
Responsible Party Gilead Sciences ( Kite, A Gilead Company )
Study Sponsor  ICMJE Kite, A Gilead Company
Collaborators  ICMJE Pfizer
Investigators  ICMJE
Study Director:Kite Study DirectorKite, A Gilead Company
PRS Account Gilead Sciences
Verification Date October 2020

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