Safety and Efficacy of KTE-C19 in Adults With Refractory Aggressive Non-Hodgkin Lymphoma

Status: Active

Description

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

Eligibility Criteria

Inclusion Criteria

  • Histologically confirmed:
  • Diffuse Large B Cell Lymphoma (DLBCL)
  • Primary Mediastinal Large B Cell Lymphoma (PMBCL)
  • Transformation Follicular Lymphoma (TFL)
  • High grade B-cell lymphoma (HGBCL)
  • Chemotherapy-refractory disease, defined as one of more of the following:
  • 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
  • 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
  • Individuals 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
  • for individual with transformed FL must have chemorefractory disease after transformation to DLBCL.
  • At least one measurable lesion per revised IWG Response Criteria
  • Age 18 or older
  • Eastern cooperative oncology group (ECOG) performance status of 0 or 1
  • Absolute neutrophil count (ANC) ≥ 1000/uL
  • Absolute lymphocyte count ≥ 100/uL
  • Platelet count ≥ 75,000/uL
  • Adequate renal, hepatic, pulmonary and cardiac function defined as:
  • Creatinine clearance (as estimated by Cockcroft Gault) > 60 mL/min
  • Serum alanine aminotransferase (ALT)/aspartate aminotransferase (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%, no evidence of pericardial effusion as determined by an echocardiogram (ECHO), and no clinically significant pleural effusion
  • Baseline oxygen saturation >92% on room air
  • 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.
  • Relapsed or refractory large B-cell lymphoma including DLBCL, PMBCL, TFL, and HGBCL after two systemic lines of therapy

Exclusion Criteria

  • 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
  • History of allogeneic stem cell transplantation
  • Prior CAR therapy or other genetically modified T cell therapy
  • 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
  • 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
  • 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
  • History or presence of CNS disorder such as seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement

Locations & Contacts

California

Duarte
City of Hope Comprehensive Cancer Center
Status: Temporarily closed to accrual
Name Not Available
La Jolla
UC San Diego Moores Cancer Center
Status: Active
Contact: Januario Enrique Castro
Email: kcmontalvo@ad.ucsd.edu
Los Angeles
UCLA / Jonsson Comprehensive Cancer Center
Status: Active
Contact: John Matthew Timmerman
Phone: 888-798-0719
Email: jtimmerman@mednet.ucla.edu
San Diego
University of California San Diego
Status: Active
Contact: Januario Enrique Castro
Phone: 858-822-5354
Email: cancercto@ucsd.edu

Iowa

Iowa City
University of Iowa / Holden Comprehensive Cancer Center
Status: Active
Name Not Available

Massachusetts

Boston
Brigham and Women's Hospital
Status: Active
Name Not Available
Dana-Farber Cancer Institute
Status: Active
Contact: Caron Alyce Jacobson
Email: gdemaeyer@partners.org

Michigan

Detroit
Wayne State University / Karmanos Cancer Institute
Status: Active
Name Not Available

Minnesota

Rochester
Mayo Clinic
Status: Active
Name Not Available

Missouri

Saint Louis
Siteman Cancer Center at Washington University
Status: Active
Name Not Available

Nebraska

Omaha
University of Nebraska Medical Center
Status: Active
Contact: Susan Blumel
Email: jill.harrison.whitaker@vanderbilt.edu

New York

Bronx
Montefiore Medical Center-Weiler Hospital
Status: Active
Contact: Ira Braunschweig
Phone: 718-920-4826
Email: ibraunsc@montefiore.org

Tennessee

Nashville
Vanderbilt University / Ingram Cancer Center
Status: Active
Name Not Available

Trial Phase & Type

Trial Phase

Phase I/II

Trial Type

Treatment

Lead Organization

Lead Organization
Kite, A Gilead Company

Trial IDs

Primary ID KTE-C19-101
Secondary IDs NCI-2015-00239, 2015-005007-86
Clinicaltrials.gov ID NCT02348216