A Phase 2 Multicenter Study Evaluating the Efficacy of KTE-X19 in Subjects with Relapsed/Refractory Mantle Cell Lymphoma (r/r MCL)
- Conditions
- Mantle Cell Lymphoma (MCL)cancer of white blood cells10025322
- Registration Number
- NL-OMON54549
- Lead Sponsor
- Kite Pharma Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 20
101. Pathologically confirmed MCL, with documentation of either overexpression
of cyclin D1 or presence of t(11;14) 102. Up to 5 prior regimens for MCL.
Cohort 1 and Cohort 2: Prior therapy must have included: - Anthracycline or
bendamustine-containing chemotherapy and - Anti-CD20 monoclonal antibody
therapy and - Ibrutinib or acalabrutinib Cohort 3: Prior therapy must have
included anthracycline, bendamustine-, or high dose cytarabine-containing
chemotherapy and anti-CD20 monoclonal antibody therapy. Subjects in Cohort 3
must not have received prior therapy with a BTKi. 103. Relapsed or refractory
disease, as defined by the following: - Disease progression after last regimen,
or - Failure to achieve a PR or CR to the last regimen 104. At least 1
measurable lesion. 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 one lymph node should be >= 2 cm 105. For subjects in cohort 1
and cohort 2 only: MRI of the brain showing no evidence of CNS lymphoma 106. At
least 2 weeks or 5 half-lives, whichever is shorter, must have elapsed since
any prior systemic therapy or BTKi (ibrutinib or acalabrutinib; as applicable
for subjects in cohort 1 and cohort 2) at the time the subject is planned for
leukapheresis, except for systemic inhibitory/stimulatory immune checkpoint
therapy. At least 3 half-lives must have elapsed from any prior systemic
inhibitory/stimulatory immune checkpoint molecule therapy at the time the
subject is planned for leukapheresis (e.g. ipilimumab, nivolumab,
pembrolizumab, atezolizumab, OX40 agonists, 4- 1BB agonists etc). 107.
Toxicities due to prior therapy must be stable and recovered to <= Grade 1
(except for clinically non-significant toxicities such as alopecia) 108. Age 18
years or older 109. Eastern cooperative oncology group (ECOG) performance
status of 0 or 1 110. ANC >= 1000/uL 111. Platelet count >= 75,000/uL. For
subjects in cohort 3 with bone marrow involvment, platelet count >50,000/uL
is acceptable 112. Absolute lymphocyte count >= 100/ uL 113. Adequate renal,
hepatic, pulmonary and cardiac function defined as: - Creatinine clearance (as
estimated by Cockcroft Gault) >= 60 cc/min - Serum ALT/AST <= 2.5 ULN - Total
bilirubin <= 1.5 mg/dl, except in subjects with Gilbert*s syndrome - Cardiac
ejection fraction >= 50%, no evidence of pericardial effusion as determined by
an ECHO, and no clinically significant ECG findings. For subjects in cohort 3,
a multigated acquisition (MUGA) scan may be used in place of ECHO. - No
clinicallly significant pleural effusion for subjects in cohort 1 and cohort 2
and no clinically significant pleural effusion, pericardial effusion, or
ascites for subjects in cohort 3. - Baseline oxygen saturation > 92% on room
air 114. Females of childbearing potential must have a negative serum or urine
pregnancy test. Females who have undergone surgical sterilization or who have
been postmenopausal for at least 2 years are not considered to be of
childbearing potential.
201. History of malignancy other than non-melanomatous skin cancer or carcinoma
in situ (e.g. cervix, bladder, breast) unless disease free for at least 3
years. 202. Autologous stem cell transplant within 6 weeks of planned KTE-X19
or axicabtagene ciloleucel infusion. 203. History of allogeneic stem cell
transplantation, with the exception of subjects in cohort 3 with no donor cells
detected on chimerism >100 days after alloSCT. 204. Prior CD19 targeted
therapy with the exception of subjects who received KTE-X19 or axicabtagene
ciloleucel in this study and are eligible for re-treatment. 205. Prior chimeric
antigen receptor therapy or other genetically modified T cell therapy 206.
History of severe, immediate hypersensitivity reaction attributed to
aminoglycosides 207. Presence of fungal, bacterial, viral, or other infection
that is uncontrolled or requiring IV antimicrobials for management. Simple UTI
and uncomplicated bacterial pharyngitis are permitted if responding to active
treatment and after consultation with the Kite Medical Monitor. 208. History of
HIV infection or acute or chronic active hepatitis B or C infection. Subjects
with a history of hepatitis infection must have cleared their infection as
determined by standard serological and genetic testing. 209. Presence of any
indwelling line or drain (e.g. percutaneous nephrostomy tube, indwelling Foley
catheter, biliary drain, or pleural/peritoneal/pericardial catheter). Ommaya
reservoirs and dedicated central venous access catheters such as a Port-a-Cath
or Hickman catheter are permitted 210. Subjects with detectable cerebrospinal
fluid malignant cells, or brain metastases, or with a history of CNS lymphoma,
cerebrospinal fluid malignant cells or brain metastases 211. History or
presence of CNS disorder, such as seizure disorder, cerebrovascular
ischemia/hemorrhage, dementia, cerebellar disease, cerebral edema, posterior
reversible encephalopathy syndrome (PRES), or any autoimmune disease with CNS
involvement 212. History of myocardial infarction, cardiac angioplasty or
stenting, unstable angina, active arrhythmias or other clinically significant
cardiac disease within 12 months of enrollment 213. Subjects with cardiac
atrial or cardiac ventricular lymphoma involvement 214. History of deep vein
thrombosis or pulmonary embolism requiring therapeutic anticoagulation within 6
months of enrollment 215. Possible requirement for urgent therapy due to
ongoing or impending oncologic emergency (eg, tumor mass effect, tumor lysis
syndrome) 216. Primary immunodeficiency 217. Any medical condition likely to
interfere with assessment of safety or efficacy of study treatment 218. History
of severe immediate hypersensitivity reaction to any of the agents used in this
study 219. Live vaccine <= 6 weeks prior to planned start of conditioning
regimen 220. Females of child-bearing potential who are pregnant or
breastfeeding because of the potentially dangerous effects of the preparative
chemotherapy on the fetus or infant 221. Subjects of both genders who are not
willing to practice birth control from the time of consent through 6 months
after the completion of KTE-X19 or axicabtagene ciloleucel. 222. In the
investigators judgment, the subject is unlikely to complete all
protocol-required study visits or procedures, includ
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Primary Endpoint:<br /><br>• Objective response rate (complete response [CR] + partial response [PR]) per<br /><br>the Lugano Classification (Cheson et al, 2014) per Independent Radiology Review<br /><br>Committee (IRRC) review.</p><br>
- Secondary Outcome Measures
Name Time Method <p>Secondary Endpoints:<br /><br>• Duration of Response<br /><br>• Best Objective Response<br /><br>• Objective response rate as determined by study investigators<br /><br>• Progression Free Survival<br /><br>• Overall Survival<br /><br>• Incidence of adverse events and clinically significant changes in laboratory<br /><br>values<br /><br>• Incidence of anti-CD19 CAR antibodies<br /><br>• Levels of anti CD19 CAR+ T cells in blood<br /><br>• Levels of cytokines in serum.<br /><br>• Changes over time in the EQ-5D scale score and VAS score<br /><br>• Changes over time in the EORTC-QLQ-C30 score (Cohort 3 only)</p><br>