Purpose

This study will be separated into 3 distinct phases designated as the Phase 1 study, Phase 2 pivotal study (Cohort 1 and Cohort 2), and Phase 2 safety management study (Cohort 3 and Cohort 4, Cohort 5 and Cohort 6). The primary objectives of this study are: - Phase 1 Study: Evaluate the safety of axicabtagene ciloleucel regimens - Phase 2 Pivotal Study; Evaluate the efficacy of axicabtagene ciloleucel - Phase 2 Safety Management Study: Assess the impact of prophylactic regimens or earlier interventions on the rate and severity of cytokine release syndrome (CRS) and neurologic toxicities

Conditions

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  1. Histologically confirmed:
  2. Diffuse Large B Cell Lymphoma (DLBCL)
  3. Primary Mediastinal Large B Cell Lymphoma (PMBCL)
  4. Transformation Follicular Lymphoma (TFL)
  5. High grade B-cell lymphoma (HGBCL)
  6. Chemotherapy-refractory disease, defined as one of more of the following:
  7. No response to last line of therapy i. Progressive disease (PD) as best response to most recent therapy regimen ii. Stable disease (SD) as best response to most recent therapy with duration no longer than 6 month from last dose of therapy OR
  8. Refractory post-autologous stem cell transplant (ASCT) i. Disease progression or relapsed less than or equal to 12 months of ASCT (must have biopsy proven recurrence in relapsed individuals) ii. If salvage therapy is given post-ASCT, the individual must have had no response to or relapsed after the last line of therapy
  9. Individuals must have received adequate prior therapy including at a minimum:
  10. anti-CD20 monoclonal antibody unless investigator determines that tumor is CD20-negative and
  11. an anthracycline containing chemotherapy regimen
  12. for individual with transformed FL must have chemorefractory disease after transformation to DLBCL.
  13. At least one measurable lesion per revised IWG Response Criteria
  14. Age 18 or older
  15. Eastern cooperative oncology group (ECOG) performance status of 0 or 1
  16. Absolute neutrophil count (ANC) ≥ 1000/uL
  17. Absolute lymphocyte count ≥ 100/uL
  18. Platelet count ≥ 75,000/uL
  19. Adequate renal, hepatic, pulmonary and cardiac function defined as:
  20. Creatinine clearance (as estimated by Cockcroft Gault) > 60 mL/min
  21. Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) < 2.5 upper limit of normal (ULN)
  22. Total bilirubin < 1.5 mg/dl, except in individuals with Gilbert's syndrome
  23. Cardiac ejection fraction >50%, no evidence of pericardial effusion as determined by an echocardiogram (ECHO), and no clinically significant pleural effusion
  24. Baseline oxygen saturation >92% on room air
  25. All individuals or legally appointed representatives/caregivers, must personally sign and date the Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved consent form before initiating any study specific procedures or activities.
  26. Relapsed or refractory large B-cell lymphoma including DLBCL, PMBCL, TFL, and HGBCL after two systemic lines of therapy

Exclusion Criteria

  1. History of malignancy other than nonmelanoma skin cancer or carcinoma in situ (e.g. cervix, bladder, breast) or follicular lymphoma unless disease free for at least 3 years
  2. History of allogeneic stem cell transplantation
  3. Prior CAR therapy or other genetically modified T cell therapy
  4. Presence of fungal, bacterial, viral, or other infection that is uncontrolled or requiring IV antimicrobials for management. Simple urinary tract infection (UTI) and uncomplicated bacterial pharyngitis are permitted if responding to active treatment
  5. 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
  6. Individuals with detectable cerebrospinal fluid malignant cells, or brain metastases, or with a history of central nervous system (CNS) lymphoma or primary CNS lymphoma, cerebrospinal fluid malignant cells or brain metastases
  7. History or presence of CNS disorder such as seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement

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

Study Design

Phase
Phase 1/Phase 2
Study Type
Interventional
Intervention Model
Single Group Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Axicabtagene Ciloleucel
A conditioning chemotherapy regimen of fludarabine and cyclophosphamide will be administered followed by investigational treatment, axicabtagene ciloleucel.
  • Biological: Axicabtagene Ciloleucel
    A single infusion of chimeric antigen receptor (CAR)-transduced autologous T cells administered intravenously at a target dose of 2 x 10^6 anti-CD19 CAR T cells/kg.
    Other names:
    • Yescarta®
  • Drug: Fludarabine
    Administered according to package insert
  • Drug: Cyclophosphamide
    Administered according to package insert

More Details

Status
Active, not recruiting
Sponsor
Kite, A Gilead Company

Study Contact

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.