57 Participants Needed

NT-I7 + CAR T-Cell Therapy for Large B-Cell Lymphoma

Recruiting at 3 trial locations
ON
HH
KS
Overseen ByKristina Stermer, MMS
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Approved in 1 JurisdictionThis treatment is already approved in other countries

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does mention that you cannot have any concurrent chemotherapy, biologic, or hormonal therapy for cancer treatment. Non-cancer-related medications, like insulin for diabetes, are allowed.

What data supports the effectiveness of the treatment NT-I7 + CAR T-Cell Therapy for Large B-Cell Lymphoma?

Research shows that a long-acting form of interleukin-7 (IL-7), called rhIL-7-hyFc, can improve the effectiveness of CAR T-cell therapy by helping these cells grow, last longer, and fight cancer better in animal models. This suggests that using rhIL-7-hyFc with CAR T-cell therapy might help treat large B-cell lymphoma more effectively.12345

Is NT-I7 (Efineptakin alfa) safe for human use?

NT-I7 (Efineptakin alfa) has been tested in humans and is generally well-tolerated. In studies, the most common side effect was a reaction at the injection site, which resolved on its own. It has been used safely in healthy volunteers and patients with conditions like HIV and glioblastoma, showing potential as a treatment option for those with low T-cell counts.12367

How is NT-I7 + CAR T-Cell Therapy different from other treatments for Large B-Cell Lymphoma?

This treatment combines CAR T-cell therapy, which uses modified immune cells to target cancer, with NT-I7, a long-acting form of interleukin-7 (a protein that boosts immune cell growth). NT-I7 enhances the expansion and persistence of CAR T-cells, potentially improving their effectiveness against tumors compared to standard CAR T-cell therapies.12368

Eligibility Criteria

Adults over 18 with relapsed/refractory Large B-cell Lymphoma who've had at least two prior treatments and are eligible for CD19 CAR T-cell therapy. They must have an ECOG performance status of 0-1, measurable disease, a life expectancy of 12+ weeks, and adequate organ function. Exclusions include severe reactions to previous CAR T-cell therapy, pregnancy, CNS lymphoma involvement, active infections or concurrent clinical study participation.

Inclusion Criteria

Hemoglobin ≥8.0 g/dL or ≥4.96 mmol/L
Subjects must have measurable disease by IWG response criteria for lymphoma [Lugano classification (3)]
AST(SGOT)/ALT(SGPT) ≤2.5 × ULN (AST and/or ALT ≤5 × ULN for subjects with liver metastasis)
See 22 more

Exclusion Criteria

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
I cannot receive treatments by injection into my muscles.
Concurrent enrollment in another clinical study unless it is an observational (noninterventional) clinical study
See 10 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Subjects are enrolled in 1 of 7 dose levels to determine the maximum tolerated dose of NT-I7

3 weeks
Multiple visits for dose administration and monitoring

Dose Expansion

Up to 15 subjects are treated with the recommended dose identified in the Dose Escalation phase

3 months
Regular visits for treatment and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 months
Periodic visits for follow-up assessments

Treatment Details

Interventions

  • NT-I7
Trial OverviewThe trial is testing the safety and effectiveness of NT-I7 (Efineptakin alfa) given after standard CD19 CAR T-cell therapies like Axicabtagene ciloleucel, Lisocabtagene Maraleucel or Tisagenlecleucel in patients with r/r LBCL. It's a Phase 1b multicenter study focusing on how well patients tolerate this combination treatment.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: NT-I7 after CAR-T (Kymriah, Yescarta, or Breyanzi) infusionExperimental Treatment4 Interventions
CAR-T infusion administered per standard of care at Day 0 followed by NT-I7 on Day 21.

Find a Clinic Near You

Who Is Running the Clinical Trial?

NeoImmuneTech

Lead Sponsor

Trials
16
Recruited
780+

Findings from Research

A new long-acting form of interleukin-7 (rhIL-7-hyFc) has been shown to significantly enhance the effectiveness of CAR T cell therapy by promoting the growth, persistence, and cytotoxicity of CAR T cells in mouse models.
This enhancement leads to long-term tumor-free survival, suggesting that rhIL-7-hyFc could be a valuable addition to CAR T cell treatments for patients with refractory hematologic malignancies.
A long-acting interleukin-7, rhIL-7-hyFc, enhances CAR T cell expansion, persistence, and anti-tumor activity.Kim, MY., Jayasinghe, R., Devenport, JM., et al.[2023]
The hybrid Fc-fused long-acting recombinant human IL-7 (rhIL-7-hyFc) significantly enhances the antitumor response by expanding CD8+ T cells in the tumor microenvironment, leading to increased tumor-reactive T cells with improved effector functions.
When combined with chemotherapy and checkpoint inhibitors, rhIL-7-hyFc not only boosts the antitumor response but also restores CD8+ T cell levels even in conditions of low T lymphocyte counts, suggesting its potential as an effective immunotherapy strategy.
Hybrid Fc-fused interleukin-7 induces an inflamed tumor microenvironment and improves the efficacy of cancer immunotherapy.Kim, JH., Kim, YM., Choi, D., et al.[2022]
In a study involving 18 patients with recurrent glioblastoma, treatment with a long-acting engineered version of interleukin-7 (rhIL-7-hyFc) significantly increased total lymphocyte count (TLC) from an average of 1131 cells/mm3 to 4356 cells/mm3, indicating its efficacy in restoring immune function.
The treatment was well-tolerated, showing no serious toxicity, and resulted in a median overall survival of 378 days and progression-free survival of 231 days, suggesting potential benefits when combined with various chemotherapy regimens.
Compassionate use of recombinant human IL-7-hyFc as a salvage treatment for restoring lymphopenia in patients with recurrent glioblastoma.Ahn, S., Park, JS., Kim, H., et al.[2023]

References

A long-acting interleukin-7, rhIL-7-hyFc, enhances CAR T cell expansion, persistence, and anti-tumor activity. [2023]
Hybrid Fc-fused interleukin-7 induces an inflamed tumor microenvironment and improves the efficacy of cancer immunotherapy. [2022]
Compassionate use of recombinant human IL-7-hyFc as a salvage treatment for restoring lymphopenia in patients with recurrent glioblastoma. [2023]
Role of CXCR3 ligands in IL-7/IL-7R alpha-Fc-mediated antitumor activity in lung cancer. [2022]
IL-7R expression and IL-7 signaling confer a distinct phenotype on developing human B-lineage cells. [2021]
hIL-7-hyFc, A Long-Acting IL-7, Increased Absolute Lymphocyte Count in Healthy Subjects. [2021]
IL-7 administration drives T cell-cycle entry and expansion in HIV-1 infection. [2021]
IL7-Fc Enhances the Efficacy of Adoptive T Cell Therapy under Lymphopenic Conditions in a Murine Melanoma Model. [2021]