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

Recruiting at 3 trial locations

Overseen By Kristina Stermer, MMS

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: NeoImmuneTech

Must not be taking: Chemotherapy, Biologic therapy

Disqualifiers: CNS involvement, Autoimmune disease, Active infection, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

57 Participants Needed

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. ^{1 2 3 4 5}

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. ^{1 2 3 6 7}

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. ^{1 2 3 6 8}

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)

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

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 Overview The 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

Group I: NT-I7 after CAR-T (Kymriah, Yescarta, or Breyanzi) infusion Experimental Treatment 4 Interventions

CAR-T infusion administered per standard of care at Day 0 followed by NT-I7 on Day 21.

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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]

IL-7/IL-7Rα-Fc treatment significantly inhibited tumor growth and improved survival in murine lung cancer models by enhancing the activity of antigen presenting cells (APCs) and T cells.

The mechanism of action involves increased levels of key cytokines (CXCL9, CXCL10, IFNγ, IL-12) and a shift towards a more effective immune response, characterized by M1 macrophage infiltration and enhanced T cell activation, which are crucial for the antitumor effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of CXCR3 ligands in IL-7/IL-7R alpha-Fc-mediated antitumor activity in lung cancer. Andersson, A., Srivastava, MK., Harris-White, M., et al.[2022]

IL-7 plays a crucial role in regulating B-cell development by suppressing premature Ig light-chain rearrangement, which is essential for proper antibody formation.

In a study examining human CD19⁺ cells in xenogeneic cultures, it was found that less than 10% of these cells had complete IGH rearrangements, indicating that IL-7 signaling is vital for the correct timing of immunoglobulin gene rearrangement during B-cell maturation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

IL-7R expression and IL-7 signaling confer a distinct phenotype on developing human B-lineage cells. Nodland, SE., Berkowska, MA., Bajer, AA., et al.[2021]

The study of hIL-7-hyFc, involving 30 healthy volunteers, demonstrated that this treatment significantly increased lymphocyte counts, particularly T-cells, with effects peaking three weeks post-administration and lasting for several weeks.

hIL-7-hyFc was well-tolerated with minimal side effects, primarily injection site reactions that resolved on their own, suggesting it could be a safe and effective option for patients with weakened T-cell immunity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

hIL-7-hyFc, A Long-Acting IL-7, Increased Absolute Lymphocyte Count in Healthy Subjects. Lee, SW., Choi, D., Heo, M., et al.[2021]

A single subcutaneous dose of recombinant human IL-7 (rhIL-7) was well tolerated in HIV-infected individuals, showing biological activity at a dose of 3 microg/kg and a maximum tolerated dose of 30 microg/kg, with mild side effects like injection site reactions and transient liver function test elevations.

rhIL-7 administration led to increased numbers of circulating CD4(+) and CD8(+) T cells, indicating its potential to enhance T cell recovery in HIV infection, although it also caused transient increases in plasma HIV-RNA levels in some patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

IL-7 administration drives T cell-cycle entry and expansion in HIV-1 infection. Sereti, I., Dunham, RM., Spritzler, J., et al.[2021]

In a study using a lymphopenic murine melanoma model, recombinant IL7-Fc significantly improved the effectiveness of adoptive cell therapy (ACT) by increasing the number of CD8+ T cells in tumors and enhancing tumor growth inhibition.

However, in an immunocompetent murine melanoma model, IL7-Fc reduced the effectiveness of ACT by promoting the expansion of endogenous T cells, which limited the proliferation of the transferred tumor-reactive T cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

IL7-Fc Enhances the Efficacy of Adoptive T Cell Therapy under Lymphopenic Conditions in a Murine Melanoma Model. Yu, EM., Cho, E., Singh, R., et al.[2021]

References

1. England pubmed.ncbi.nlm.nih.gov

A long-acting interleukin-7, rhIL-7-hyFc, enhances CAR T cell expansion, persistence, and anti-tumor activity. [2023]

2. Australia pubmed.ncbi.nlm.nih.gov

Hybrid Fc-fused interleukin-7 induces an inflamed tumor microenvironment and improves the efficacy of cancer immunotherapy. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Compassionate use of recombinant human IL-7-hyFc as a salvage treatment for restoring lymphopenia in patients with recurrent glioblastoma. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Role of CXCR3 ligands in IL-7/IL-7R alpha-Fc-mediated antitumor activity in lung cancer. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

IL-7R expression and IL-7 signaling confer a distinct phenotype on developing human B-lineage cells. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

hIL-7-hyFc, A Long-Acting IL-7, Increased Absolute Lymphocyte Count in Healthy Subjects. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

IL-7 administration drives T cell-cycle entry and expansion in HIV-1 infection. [2021]

8. Switzerland pubmed.ncbi.nlm.nih.gov

IL7-Fc Enhances the Efficacy of Adoptive T Cell Therapy under Lymphopenic Conditions in a Murine Melanoma Model. [2021]