Emapalumab for Low Blood Cell Count

Overseen By Paolo Strati, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: IV antimicrobials

Disqualifiers: History of malignancy, HIV, others

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

Prior Safety Data This treatment has passed at least one previous human trial

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

Compensation: Varies

Number of Visits: Unknown

Duration: 16 weeks

32 Participants Needed

Trial Summary

What is the purpose of this trial?

To look at the safety and effectiveness of emapalumab for the treatment of prolonged severe cytopenia in participants with LBCL who receive CART.

Do I need to stop my current medications to join the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor to get a clear answer based on your specific situation.

What makes the drug Emapalumab unique for treating low blood cell count?

Emapalumab is unique because it specifically targets and neutralizes interferon gamma, a protein involved in inflammation, which is different from other treatments that may not target this pathway. This mechanism can be particularly beneficial in conditions where excessive inflammation is a problem. ^{1 2 3 4 5}

Research Team

Paolo Strati

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for individuals with LBCL who have severe, prolonged low blood cell counts after CAR T-cell therapy. Specific eligibility details are not provided, but typically participants must meet certain health standards and not have conditions that could interfere with the study or their safety.

Inclusion Criteria

Baseline oxygen saturation > 92% on room air

I have not had a menstrual period for at least 12 months.

Serum alanine transaminase (ALT) / aspartate transaminase (AST) ≤ 2.5 upper limit of normal (ULN), independently from etiology

Exclusion Criteria

Participants will be ineligible for this study if they meet the following criteria:

I am pregnant or breastfeeding.

Any medical condition likely to interfere with assessment of safety or efficacy of study treatment in the investigator's opinion

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive emapalumab at one of two dose levels for the treatment of prolonged severe cytopenia

16 weeks

Regular visits for dose administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Long-term follow-up

Participants are monitored for adverse events and long-term outcomes

Up to 1 year

Treatment Details

Interventions

• Emapalumab

Trial Overview The trial is testing emapalumab to see if it's safe and can help treat people with long-lasting severe cytopenia (low white blood cells, anemia, low platelet count) following CAR T-cell therapy for LBCL.

Participant Groups

Group I: Emapalumab Experimental Treatment 1 Intervention

If you are found to be eligible to take part in this research study, you will be assigned to 1 of 2 dose levels of emapalumab, based on when you enroll on the study. Up to 16 participants will receive each dose level of the study drug. * The first group of 5 participants will be enrolled at the lower dose level. * Depending on the safety data seen in this first group, the next 11 participants will be enrolled at the lower dose. * After reviewing the early safety data from that first group of 16 participants, the study team will enroll the next 5 participants at the higher dose level and be checked for serious side effects. * Depending on the safety information from the first 5 participants in the higher dose level group, the other 11 will then be enrolled.

Emapalumab is already approved in United States for the following indications:

Approved in United States as Gamifant for:

• Primary hemophagocytic lymphohistiocytosis (HLH) with refractory, recurrent or progressive disease or intolerance with conventional HLH therapy

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Sobi, Inc.

Industry Sponsor

Trials

14

Recruited

1,000+

Findings from Research

Mavrilimumab, a GM-CSF receptor-α antibody, showed significant clinical benefits in a Phase II trial for moderate rheumatoid arthritis, particularly in the 100 mg dosage group compared to placebo.

The drug's unique mechanism of targeting GM-CSF signaling, along with its demonstrated efficacy and safety, suggests it could effectively induce remission and improve overall health outcomes for patients with rheumatoid arthritis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mavrilimumab, a human monoclonal GM-CSF receptor-α antibody for the management of rheumatoid arthritis: a novel approach to therapy. Nair, JR., Edwards, SW., Moots, RJ.[2019]

Autoantibodies against the FcgammaRIIIb receptor can prolong the survival of neutrophils (PMNs) by triggering anti-apoptotic signals, which may help in non-organ-specific diseases.

The mechanism involves signaling through FcgammaRIIIb and CD11b, leading to the production of granulocyte colony-stimulating factors that delay apoptosis, suggesting a potential therapeutic target for modulating immune responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pathogenic effects of anti-Fc gamma receptor IIIb (CD16) on polymorphonuclear neutrophils in non-organ-specific autoimmune diseases. Youinou, P., Durand, V., Renaudineau, Y., et al.[2019]

A new genotyping assay using polymerase chain reaction has been developed to accurately identify the granulocyte antigens NA1 and NA2, which are important in various clinical conditions like neonatal neutropenia and transfusion-related complications.

The assay showed a 100% concordance rate with traditional serologic typing, demonstrating its reliability, and revealed specific gene frequencies for NA1 and NA2 across different ethnic groups, which can aid in understanding population-specific risks in related medical conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Determination of neutrophil antigen gene frequencies in five ethnic groups by polymerase chain reaction with sequence-specific primers. Hessner, MJ., Curtis, BR., Endean, DJ., et al.[2022]

In a study of 17 patients undergoing allogeneic stem cell transplantation (allo-SCT), major mismatches in neutrophil antigens (NA1 and NA2) did not significantly affect the engraftment of neutrophils or the incidence of post-engraftment neutropenia.

The findings suggest that using leukocyte depletion filters and administering G-CSF after transplantation may mitigate the impact of NA2 antigen mismatches on neutrophil engraftment, although the study's small sample size limits the statistical power of these conclusions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Little impact of donor/recipient major mismatch for neutrophil-specific antigen NA2 on neutrophil recovery after allogeneic SCT. Inukai, T., Goi, K., Tezuka, T., et al.[2009]

In a phase 2 study involving subjects with rheumatoid arthritis, mavrilimumab significantly improved disease activity, with 55.7% of treated participants achieving a meaningful reduction in Disease Activity Score compared to 34.7% in the placebo group.

The treatment was generally safe, with most adverse events being mild to moderate, and no serious infections or significant hypersensitivity reactions reported, indicating a favorable safety profile for mavrilimumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of mavrilimumab in subjects with rheumatoid arthritis. Burmester, GR., Weinblatt, ME., McInnes, IB., et al.[2022]

References

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

Mavrilimumab, a human monoclonal GM-CSF receptor-α antibody for the management of rheumatoid arthritis: a novel approach to therapy. [2019]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Pathogenic effects of anti-Fc gamma receptor IIIb (CD16) on polymorphonuclear neutrophils in non-organ-specific autoimmune diseases. [2019]

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

Determination of neutrophil antigen gene frequencies in five ethnic groups by polymerase chain reaction with sequence-specific primers. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Little impact of donor/recipient major mismatch for neutrophil-specific antigen NA2 on neutrophil recovery after allogeneic SCT. [2009]

5. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of mavrilimumab in subjects with rheumatoid arthritis. [2022]