Trial Title:
Itacitinib Pre-modulation in DLBCL Receiving CAR T Cell Therapy
NCT ID:
NCT05757219
Condition:
Diffuse Large B Cell Lymphoma
Conditions: Official terms:
Lymphoma
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Axicabtagene ciloleucel
Conditions: Keywords:
CAR-T
chimeric antigen receptor (CAR) T-cell therapy
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Itacitinib
Description:
Participants start itacitinib 200 mg PO once daily within 1-4 days after apheresis while
awaiting CAR-T-cell manufacturing, which is expected to take approximately from week -4
until day -7. Patients will remain on itacitinib 200 mg PO once daily from initiation
until 30 days post-CAR-T-cell therapy (Day 30) including throughout lymphodepleting
chemotherapy period (Days -5, -4, -3) and axi-cel infusion (Day 0) for a total of
approximately 58 doses.
Arm group label:
Pre-Modulation Treatment
Intervention type:
Biological
Intervention name:
Chimeric antigen receptor (CAR) T-cell therapy
Description:
Yescarta is an autologous anti-CD19 CAR T cell therapy manufactured from the patient's
own T cells, which have been extracted and then reprogrammed with CAR molecules to help
the T cells recognize cancer cells. The reengineered T cells are infused back into the
patient to attack the cancer.
Arm group label:
Pre-Modulation Treatment
Other name:
YESCARTA
Other name:
Axi-cel
Summary:
The purpose of the study is to assess the safety and efficacy of once daily itacitinib
oral administration in participants with diffuse large B-cell lymphoma (DLBCL) who will
receive CAR-T cell therapy with axicabtagene ciloleucel (axi-cel).
Detailed description:
This is a phase 2, single-arm, open-label study to assess the safety and efficacy of once
daily itacitinib oral administration in patients with diffuse large B-Cell lymphoma
(DLBCL) who will receive CAR-T-cell therapy with axicabtagene ciloleucel (Axi-cel) and
have been found to have high levels of systemic inflammation. Approximately n=27 adult
males and females, 18 years or older, who will receive treatment for diffuse large B-cell
lymphoma (DLBCL) at the Moffitt Cancer Center with a ferritin level greater than 400
ng/ml and C-reactive protein (CRP) level greater than 2 mg/dl (20 mg/l) at screening will
be enrolled. Study regimen will consist of itacitinib 200 mg PO QD beginning at time of
apheresis approximately 4-6 weeks prior to CAR-T-cell therapy and will continue until Day
30 (30 Days Post-CAR-T-cell therapy). The exact number of days between apheresis and CAR
T cell infusion may vary based on CAR T cell manufacturing turnaround. A single infusion
of axi-cel therapy will be administered on Day 0. Investigators hypothesize that
pre-modulation with itacitinib started approximately 4 weeks prior to CAR-T-cell therapy
with axi-cel will improve patient outcomes in those patients with diffuse large B-cell
lymphoma (DLBCL) who express high levels of systemic inflammation.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Patients with a histologically confirmed diagnosis of diffuse large B-cell lymphoma
(DLBCL) who plan to receive treatment at the Moffitt Cancer Center/
- Adult males or females who are 18 years of age or older at time of signing informed
consent.
- Must have ability to comprehend and the willingness to sign written informed consent
for study participation.
- Eligible to receive CAR-T cell therapy (axicabtagene ciloleucel) for DLBCL and
histological variants.
- Patients must have a serum ferritin level above 400 mg/mL and C-reactive protein
level above 2 mg/dL (20 mg/L) at screening.
- ECOG performance status 0 to 2.
- The effects of Itacitinib on the developing human fetus are unknown. For this reason
and because Janus kinase (JAK)1-selective inhibitors as well as other therapeutic
agents used in this trial are known to be teratogenic, women of child-bearing
potential and men must agree to use adequate contraception (hormonal or barrier
method of birth control; abstinence) prior to study entry and for the duration of
study participation as outlined in criteria below: (a) Men must agree to take
appropriate precautions to avoid fathering children (with at least 99% certainty)
from screening through safety follow up and must refrain from donating sperm during
this period. Permitted methods that are at least 99% effective in preventing
pregnancy should be communicated to the participants in their understanding
confirmed.(b) Women of childbearing potential must have a negative serum pregnancy
test at screening and before the first dose of Day 1 and must agree to take
appropriate precautions to avoid pregnancy (with at least 99% certainty) from
screening through safety follow up. Permitted methods that are at least 99%
effective in preventing pregnancy should be communicated to the participants and
their understanding confirmed. (c) Women of non-childbearing potential (ie,
surgically sterile with a hysterectomy and/or bilateral oophorectomy OR >= 12 months
of amenorrhea) are eligible.
- Patients must be ineligible for stem cell transplant at screening on the basis of
active lymphoma.
- Patients must meet laboratory parameters at screening as defined in protocol
Exclusion Criteria:
- Patients who are currently receiving or who have received any investigational study
agent ≤4 weeks prior to screening visit are ineligible.
- Prior treatment with chimeric antigen receptor (CAR) T-cell therapy.
- Participants with clinically significant or uncontrolled cardiac disease, including
unstable angina, acute myocardial infarction within 6 months from screening, New
York Health Association III or IV heart failure, and circulatory collapse requiring
vasopressor or inotropic support
- Participants with arrhythmias that are not stable on a medical management program
within 2 weeks of screening are also excluded.
- Participants with arrhythmias that are not stable on a medical management program
within 2 weeks of screening are also excluded.
- Evidence of active uncontrolled/untreated infection (viral, bacterial, fungal,
opportunistic) of any origin.
- Participants with a known history or prior diagnosis of immunologic or
inflammatory/autoimmune disease affecting the CNS, and unrelated to their disease
under study or previous treatment.
- Known positive Human immunodeficiency virus (HIV) status.
- Participants with evidence of active and/or chronic hepatitis B virus (HBV)
infection, HBV viral load must be undetectable on suppressive therapy, if indicated.
- Participants with a history of hepatitis C virus (HCV) infection, HCV must have been
treated and cured.
- Participants who require the concurrent use of chronic systemic steroids or
immunosuppressant medications. Steroids should not be given within 5 days prior to
leukapheresis. Concomitant bridging steroids (section 6.6) are allowed after
leukapheresis.
- Known hypersensitivity or severe reaction to itacitinib, similar compounds, or
excipients or itacitinib.
- Participants who have not recovered from adverse events (AEs) due to prior
anti-cancer therapy (i.e., have residual toxicities > Grade 1), with the exception
of stable Grade 2 peripheral neuropathy and/or any grade alopecia.
- Pregnant or nursing (breast-feeding) women are excluded from this study because
there is an unknown but potential risk to using itacitinib in pregnant or nursing
women.
- Any condition that would, in the investigator's judgement, interfere with full
participation in the study, including administration of itacitinib and attending
required study visits (if outpatient); pose a significant risk to the participant;
or interfere with interpretation of study data.
- Inability of the participant to swallow and retain oral medication.
- Participants receiving any medications or substances that are strong inhibitors of
CYP3A4 are ineligible. As part of the enrollment/informed consent procedures, the
participant will be counseled on the risk of interactions with other agents and what
to do if new medications need to be prescribed or if the participant is considering
a new over-the-counter medicine or herbal product.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Moffitt Cancer Center
Address:
City:
Tampa
Zip:
33617
Country:
United States
Status:
Recruiting
Contact:
Last name:
Kelsey Hildreth
Phone:
813-745-0667
Email:
kelsey.hildreth@moffitt.org
Investigator:
Last name:
Michael Jain, MD, PhD
Email:
Principal Investigator
Investigator:
Last name:
Julio Chavez, MD, MS
Email:
Sub-Investigator
Investigator:
Last name:
Rawan Faramand, MD
Email:
Sub-Investigator
Investigator:
Last name:
Farhad Khimani, MD
Email:
Sub-Investigator
Investigator:
Last name:
Aleksandr Lazaryan, MD, MPH, PhD
Email:
Sub-Investigator
Investigator:
Last name:
Hien Liu, MD
Email:
Sub-Investigator
Investigator:
Last name:
Frederick Locke, MD
Email:
Sub-Investigator
Investigator:
Last name:
Taiga Nishihori, MD
Email:
Sub-Investigator
Investigator:
Last name:
Javier Pinilla, MD, PhD
Email:
Sub-Investigator
Investigator:
Last name:
Bijal Shah, MD, MS
Email:
Sub-Investigator
Start date:
May 19, 2023
Completion date:
December 2025
Lead sponsor:
Agency:
H. Lee Moffitt Cancer Center and Research Institute
Agency class:
Other
Collaborator:
Agency:
Incyte Corporation
Agency class:
Industry
Source:
H. Lee Moffitt Cancer Center and Research Institute
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05757219
https://www.moffitt.org/clinical-trials-research/clinical-trials/
