Relapsed/Refractory Large B-cell Lymphoma With NT-I7 Post-CD19 CAR T-cell Therapy
- Conditions
- Refractory High Grade B-Cell LymphomaRefractory Transformed Follicular Lymphoma to Diffuse Large B-Cell LymphomaRefractory Diffuse Large B-Cell Lymphoma, Not Otherwise SpecifiedRefractory Diffuse Large B-cell LymphomaRecurrent Diffuse Large B-Cell Lymphoma
- Interventions
- Registration Number
- NCT05075603
- Lead Sponsor
- NeoImmuneTech
- Brief Summary
This is a multicenter Phase 1b study evaluating the safety, tolerability, and preliminary anti-tumor activity of NT-I7 administration following standard of care CD19 CAR T-cell therapy for eligible subjects with r/r LBCL.
- Detailed Description
This is a multicenter Phase 1b study evaluating the safety, tolerability, and preliminary anti-tumor activity of NT-I7 administration following standard of care CD19 CAR T-cell therapy for eligible subjects with r/r LBCL. The study consists of a Dose Escalation phase followed by a Dose Expansion phase.
In the Dose Escalation phase, subjects will be enrolled in 1 of 7 dose levels, starting with 60 µg/kg and up to 720 µg/kg. A dose schedule for an individual dose level will not be taken into expansion until the Dose Escalation phase has been completed or a maximum tolerated dose (MTD) has been determined, whichever occurs first.
In the Dose Expansion phase, up to 15 subjects will be enrolled and treated with the recommended dose identified in the Dose Escalation phase.
Up to 17- 42 subjects in the Dose Escalation phase, and up to 15 subjects in the Dose Expansion phase will be enrolled at approximately 20 study centers.
Treatment Plan:
NT-I7 (aka rhIL-7-hyFc, efineptakin alpha), Tisagenlecleucel (Kymriah®), Axicabtagene ciloleucel (Yescarta®), Lisocabtagene Maraleucel (Breyanzi®)
\*CAR-T Therapy will be administered per manufacturer's recommendations and in accordance with FDA prescribing guidelines and best institutional practices for standard of care use.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 57
Not provided
Subjects meeting any of the following criteria are not eligible for enrollment in the study:
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In Dose Escalation phase: Grade ≥3 CRS or ICANS post-CD19 CAR T-cell infusion. Note: Grade 1 or 2 CRS or ICANs must be completely resolved >3 days prior to NT-I7 injection
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In Dose Expansion phase: Grade ≥3 CRS or ICANS post-CD19 CAR T-cell infusion. Note: Grade 1 or 2 CRS or ICANS must be completely resolved >3 days prior to NT-I7 injection
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Pregnant, lactating or breastfeeding or expecting to conceive or father children within the study duration from screening through 120 days after the last dose of study treatment.
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This exclusion criteria has been removed and remains as a placeholder.
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Subjects with documented current central nervous system (CNS) involvement by lymphoma are to be excluded from study participation.
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Any concurrent chemotherapy or biologic or hormonal therapy for cancer treatment.
Note: Concurrent use of hormones for noncancer-related conditions (e.g., insulin for diabetes and hormone replacement therapy) is acceptable. In addition, local treatment (eg, by local surgery or radiotherapy) of isolated lesions for palliative intent is acceptable beyond the DLT evaluation period with prior consultation and agreement with the medical monitor.
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Subjects who have autoimmune disease history for the past 2 years, including but not limited to systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Bell's palsy, Guillain-Barre syndrome, multiple sclerosis, vasculitis, or glomerulonephritis. The following are exceptions to this criterion:
- Subjects with vitiligo or alopecia.
- Subjects with type 1 diabetes mellitus.
- Subjects with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement
- Psoriasis not requiring systemic treatment.
- NOTE: Diverticulitis that is not associated with inflammatory bowel disease is not considered exclusionary (e.g., subjects who do not have active diarrhea due to chronic diverticulitis).
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Have active and clinically relevant bacterial, fungal, viral, or TB infection, including known Hepatitis A, B, or C or HIV (testing not required).
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Concurrent enrollment in another clinical study unless it is an observational (noninterventional) clinical study.
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Receipt of any conventional or investigational anticancer therapy, not otherwise specified above, within 30 days prior to NT-I7 injection.
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Unresolved toxicities from prior anticancer therapy, defined as having not resolved to NCI CTCAE v5.0 Grade ≤ 1 with the exception of alopecia and laboratory values listed per the inclusion criteria. Subjects with irreversible toxicity that is not reasonably expected to be exacerbated by any of the investigational products may be included (e.g., hearing loss, peripheral neuropathy) after consultation with the medical monitor.
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Receipt of live, attenuated vaccine within 30 days prior to NT-I7 injection. Note: Subjects, if enrolled, should not receive live vaccine during the study and through 30 days after NT-I7 injection, whichever is longer. The administration of killed vaccines is permitted at any time.
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Has had an allogenic tissue/solid organ transplant or bone marrow transplant.
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Subjects for whom intramuscular therapy is contraindicated.
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Has clinically significant cardiac disease, including, but not limited to, any of the following:
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Uncontrolled atrial fibrillation
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Congestive Heart Failure NYHA Class ≥ 2
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Or any of the following within 6 months prior to Baseline, Day 0 CAR-T administration:
- Unstable angina
- Myocardial infarction
- Coronary artery bypass grafting
- Coronary angioplasty
- Coronary stenting
- Clinically significant cardiac arrhythmia and/or conduction abnormality
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History of other clinically significant cardiac disease that, in the opinion of the Investigator or designee, is a contraindication to study treatment is also excluded.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description NT-I7 after CAR-T (Kymriah, Yescarta, or Breyanzi) infusion Tisagenlecleucel CAR-T infusion administered per standard of care at Day 0 followed by NT-I7 on Day 21. NT-I7 after CAR-T (Kymriah, Yescarta, or Breyanzi) infusion Axicabtagene ciloleucel CAR-T infusion administered per standard of care at Day 0 followed by NT-I7 on Day 21. NT-I7 after CAR-T (Kymriah, Yescarta, or Breyanzi) infusion Lisocabtagene Maraleucel CAR-T infusion administered per standard of care at Day 0 followed by NT-I7 on Day 21. NT-I7 after CAR-T (Kymriah, Yescarta, or Breyanzi) infusion Efineptakin alfa CAR-T infusion administered per standard of care at Day 0 followed by NT-I7 on Day 21.
- Primary Outcome Measures
Name Time Method To determine the Maximum Tolerated Dose (MTD) 21 Days The MTD will be defined as the dose of NT-I7 that yields a DLT rate ≤ 33%.
To determine the Recommended Phase 2 Dose (RP2D) 21 Days Determination of the RP2D: The RP2D will be based on an accumulation of all available data. All available data including clinical Pharmacokinetic, Pharmacodynamic, anti-tumor activity (including best overall response rate) and safety, and nonclinical pharmacology data will be pooled. Integrated dose-response and exposure-response analyses will be conducted to determine the RP2D
For Dose Escalation Phase: Incidence of adverse events (AE) 21 Days According to NCI Common Terminology Criteria for Adverse Events (CTCAE) v5.0
Incidence of Dose Limiting Toxicities (DLT) 21 Days DLT is defined as any AE occurring within the first 21 days after NT-I7 injection that is considered to be at least possibly, probably, or definitely related to the study treatment (NT-I7) per the investigator, and that meets at least one of the non-hematologic or hematologic criteria listed below.
- Secondary Outcome Measures
Name Time Method Rates of grade 3 and higher cytokine release syndrome (CRS) Up to 3 months Grading of CRS will be based on American Society for Transplantation and Cellular Therapy (ASTCT) guidelines.
Measurement of Overall Survival (OS) up to 3 months Overall survival (OS) defined as the time from first study treatment (Day 1) to death from any cause.
The effect of NT-I7 on CAR-T cells expansion by fluorescence-activated cell sorting (FACS) Up to 3 months Measurement of Duration of Response (DOR) up to 3 months Duration of Response (DoR) for the responders defined as the time from the first occurrence of a documented objective response (Partial Response \[PR\] or Complete Response \[CR\]) to the time of the first documented disease progression or death from any cause, whichever occurs first, per the Lugano classification as determined by the investigator.
Measurement of Progression-Free Survival (PFS) up to 3 months Progression Free Survival (PFS) defined as the time from the first study treatment (Day 1) to the first occurrence of progression or death from any cause, whichever occurs first, per the Lugano classification as determined by the investigator.
Rates of grade 3 and higher immune effector cell associated neurotoxicity syndrome (ICANS) Up to 3 months Grading of ICANS will be based on American Society for Transplantation and Cellular Therapy (ASTCT) guidelines.
The effect of NT-I7 on CAR-T cells expansion by Quantitative DNA Polymerase Chain Reaction (PCR) Up to 3 months
Trial Locations
- Locations (4)
Duke Cancer Institute
🇺🇸Durham, North Carolina, United States
City of Hope
🇺🇸Duarte, California, United States
Barbara Ann Karmanos Cancer Hospital dba Karmanos Cancer Center
🇺🇸Detroit, Michigan, United States
Washington University in St. Louis
🇺🇸Saint Louis, Missouri, United States