A Phase 1 Open-label, Multicenter Study Evaluating the Safety and Efficacy of KITE-363, an Autologous Anti-CD19/CD20 CAR T-cell Therapy, in Subjects With Relapsed and/or Refractory B-cell Lymphoma
- Conditions
- lymph node cancernon-Hodgkin's B-cell lymphoma10025320
- Registration Number
- NL-OMON53464
- Lead Sponsor
- Kite Pharma, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Pending
- Sex
- Not specified
- Target Recruitment
- 7
1) Subjects with any of the following B-cell lymphomas as defined by the WHO 2016 criteria, as determined by the investigator, are eligible for the study as defined below: a) Histologically confirmed r/r LBCL (including all subtypes in WHO 2016 as well as transformed iNHL) and r/r FL Grade 3b with r/r disease after at least 2 lines of systemic therapy that can include auto-SCT. Or subjects with chemorefractory disease to first-line therapy (primary refractory disease) by satisfying any of the following criteria: - Progressive disease (PD) as the best response to first-line therapy - Stable disease (SD) as the best response after at least 4 cycles of first-line therapy (eg, 4 cycles of R-CHOP) with a SD duration of no longer than 6 months from the last dose of therapy - Partial response (PR) as best response after at least 6 cycles of first-line therapy (eg, 6 cycles of R-CHOP) i) Prior therapy must have included an anti-CD20 mAb and an anthracycline-containing chemotherapy regimen. ii) Subjects with transformed iNHL are eligible if r/r after 1 line of therapy to account for prior therapy given before transformation if they received at least 1 line of therapy prior to transformation. b) Histologically confirmed iNHL (including the subtypes below), with r/r disease after at least 2 lines of therapy. SD (without relapse) > 1 year from completion of the last therapy is not eligible. SD (without relapse) < 1 year from completion of therapy is eligible. i) Subtypes include the following: (1) Grade 1, 2, or 3a FL (2) Nodal, extranodal, or splenic MZL ii) Prior therapy must have included an anti-CD20 mAb combined with an alkylating agent c) Histologically confirmed NLPHL with r/r disease after at least 2 lines of systemic chemotherapy d) Histologically confirmed B-cell lymphoma, unclassifiable (with features intermediate between DLBCL and cHL) with r/r disease after at least 2 lines of systemic chemotherapy 2) At least 1 measurable lesion according to the International Working Group (IWG) Lugano Response Criteria for Malignant Lymphoma. Lesions that have been previously irradiated will be considered measurable only if progression has been documented following completion of radiation therapy. If the only measurable disease is lymph-node disease, at least 1 lymph node should be >= 1.5 cm. 3) The following washout periods must be satisfied: a) At least 2 weeks or 5 half-lives, whichever is shorter, must have elapsed since any prior systemic therapy at the time the subject is planned for leukapheresis, except for systemic inhibitory/stimulatory immune checkpoint therapy and anti-CD20 mAb therapy. b) At least 3 half-lives must have elapsed after any prior systemic inhibitory/stimulatory immune checkpoint molecule therapy at the time the subject is planned for leukapheresis (eg, ipilimumab, nivolumab, pembrolizumab, atezolizumab, OX40 agonists, and 4-1BB agonists). c) At least 28 days must have elapsed since any prior anti-CD20 mAb therapy before the KITE-363 infusion. d) At least 4 weeks must have elapsed after any prior immunosuppression therapy before the KITE-363 infusion. Note: This criterion does not apply to subjects who receive bridging Please refer to Table 5 for list of allowed bridging therapy agents. 4) Prior anti-CD19 and anti-CD20 targeted therapies are allowed if administered at least 28 days (if monoclonal antibody) or 3 months (if CAR T-cell product) before the KITE-363 infusion. CD19 and/or CD20 expression must be confirmed, as p
1) Grade 4 CRS or Grade 4 neurologic toxicity attributed to prior treatment
with a CAR T-cell therapy or other genetically modified T-cell therapy
targeting CD19 and/or CD20
2) History of malignancy other than nonmelanoma skin cancer or carcinoma in
situ (eg, cervix, bladder, or breast) unless the subject has been disease free
and without anticancer therapy for at least 3 years. Subjects with asymptomatic
localized low-grade prostate cancer for which a watch-and-wait approach is
standard of care are eligible.
3) History of Richter*s transformation of chronic leukemic lymphoma, small
lymphocytic lymphoma, or lymphoplasmacytic lymphoma
4) History of allo-SCT except if no donor cells are detected on chimerism more
than 100 days after allo-SCT, the patient is off all immunosuppression, and
there is no evidence of active graft-versus-host disease of any grade
5) Auto-SCT within 6 weeks before the planned KITE-363 infusion
6) History of a severe, immediate hypersensitivity reaction attributed to
aminoglycosides
7) Presence of fungal, bacterial, viral, or other infection that is
uncontrolled or requires IV antimicrobials for management. Note: Simple urinary
tract infections and uncomplicated bacterial pharyngitis are permitted if the
subject is responding to active treatment and the criteria of being afebrile
(i.e. temperature < 38°C).
8) Known history of human immunodeficiency virus (HIV) infection, hepatitis B
(hepatitis B surface antigen positive) infection, or hepatitis C
(anti-hepatitis C virus [HCV] positive) infection. History of a hepatitis B or
C infection is permitted if the viral load is undetectable per quantitative
polymerase chain reaction (PCR) or nucleic acid testing. Note: Subjects who are
seropositive for HBV are eligible if they are HBsAg-negative and negative for
viral DNA. Subjects who are seropositive because of HBV vaccination are
eligible. Subjects on prophylactic and suppressive antiviral medications
against HBV and/or HCV administered per institutional or clinical practice
guidelines are eligible.
9) Presence of any indwelling line or drain (eg, percutaneous nephrostomy tube,
indwelling Foley catheter, biliary drain, G/J-tube or
pleural/peritoneal/pericardial catheter). Ommaya reservoirs or other dedicated
central venous access catheters such as a Port-a-Cath or Hickman catheter are
permitted.
10) Subjects with detectable CSF malignant cells or brain metastases or a
history of central nervous system (CNS) lymphoma, primary CNS lymphoma, or
spinal epidural involvement.
For remaining exclusion criteria, see the Protocol.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Primary Endpoints:<br /><br>• Phase 1a: Incidence of adverse events (AEs) defined as dose<br /><br>-limiting toxicities (DLTs)<br /><br>Phase 1b: ORR (CR +PR) (per Lugano 2014)<br /><br>Secondary Endpoints:<br /><br>• Incidence of AEs and serious AEs (SAEs)<br /><br>• TTNT, CR rate, DOR, PFS, and OS (per Lugano 2014 )<br /><br>• Incidence of antibodies to KITE-363 CARs after the KITE*363 infusion<br /><br>• Levels of analytes (including cytokines) and KITE-363 CAR T cells in the<br /><br>blood after the KITE-363 infusion</p><br>
- Secondary Outcome Measures
Name Time Method <p>Exploratory Endpoints:<br /><br>• Levels of cytokines, KITE-363 CAR T cells, T cells, and myeloid cells in the<br /><br>CSF after treatment with KITE-363<br /><br>• Presence and levels of CD19, CD20, and other B-cell antigens in relation to<br /><br>the presence and activity of KITE-363<br /><br>• Product characteristics of pre-infusion KITE-363<br /><br>• Minimal residual disease (MRD) negative response rate</p><br>