Pre-Transplant Inflammation Treatment for Immune System Disorders

Recruiting at 11 trial locations

Overseen By Roni Tamari, MD

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Disqualifiers: Uncontrolled infection, Previous allo-HCT, HIV/HTLV, Pregnancy, 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

Compensation: Varies

Number of Visits: 4

39 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine whether emapalumab (an immunotherapy drug) or a combination of fludarabine and dexamethasone helps individuals with certain immune system disorders prepare for a stem cell transplant. Researchers seek to understand if these treatments can reduce inflammation and support the growth of new immune cells after the transplant. Individuals diagnosed with a primary immune regulatory disorder or an autoinflammatory condition, who are preparing for their first stem cell transplant, might be suitable candidates. This includes those experiencing ongoing inflammation or having conditions affecting their immune responses. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Previous studies have raised safety concerns about emapalumab. Serious side effects occurred in about 53% of patients, including infections and stomach problems. Emapalumab can weaken the immune system, increasing the risk of infections.

Research has shown that combining fludarabine and dexamethasone is generally safe before stem cell transplants. These treatments prepare the body for new stem cells by reducing inflammation and are usually well-tolerated.

Prospective trial participants should consult their doctor to understand the potential risks and benefits based on this information. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they offer new strategies for managing immune system disorders, specifically targeting inflammation before a stem cell transplant. Unlike traditional treatments that generally aim to suppress the immune response broadly, emapalumab is unique as it specifically targets interferon-gamma, a key player in certain immune-mediated diseases. This targeted approach could potentially offer more precise control of inflammation with fewer side effects. Meanwhile, the combination of fludarabine and dexamethasone provides a more generalized suppression of inflammation, which might be beneficial for broader autoinflammatory conditions. These treatments could provide more tailored pre-transplant preparation, improving outcomes for patients undergoing stem cell transplants.

What evidence suggests that this trial's treatments could be effective for immune system disorders?

In this trial, participants will receive different treatments to prepare for a stem cell transplant. Research has shown that emapalumab, administered to Group A, effectively treats conditions with an overactive immune system. One study found that 54% of patients with primary HLH, a severe immune disorder, responded well to emapalumab, and many successfully underwent a stem cell transplant afterward. This suggests that emapalumab could help prepare patients for transplants by reducing inflammation.

Participants in Group B will receive a combination of fludarabine and dexamethasone. Past patients with certain inflammatory conditions have shown improvement with this combination. It may help reduce inflammation and prepare the body for a stem cell transplant by calming the immune system. Both treatments in this trial aim to enhance transplant success by controlling inflammation. ^{6 7 8 9 10}

Who Is on the Research Team?

Andromachi Scaradavou, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for people with a primary immune regulatory disorder (PIRD) and/or an autoinflammatory condition who need a stem cell transplant. They should have good organ function, be able to handle cytoreduction, and not have had previous transplants. Pregnant or breastfeeding women, HIV/HTLV-positive individuals, and those unwilling to use contraception are excluded.

Inclusion Criteria

I am eligible for a first allo-HCT due to my immune disorder and can tolerate the required treatment.

Exclusion Criteria

Uncontrolled infection at the time of enrollment, Patients who have undergone previous allo-HCT, Patient seropositivity for HIV I/II and/or HTLV I/II, Females who are pregnant or breastfeeding, Patients unwilling to use contraception during the study period, Patient or parent or guardian unable to give informed consent or unable to comply with the treatment protocol including research tests.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-Transplant Treatment

Participants receive emapalumab or a combination of fludarabine and dexamethasone to reduce inflammation before stem cell transplant

3 weeks

4 visits (in-person) for emapalumab group, 5 visits (in-person) for fludarabine and dexamethasone group

Stem Cell Transplant

Participants undergo the stem cell transplant procedure

1 week

Follow-up

Participants are monitored for engraftment and overall survival

1 year

Regular visits as per protocol

Long-term Follow-up

Participants are monitored for overall survival and long-term outcomes

5 years

What Are the Treatments Tested in This Trial?

Interventions

• Dexamethasone
• Emapalumab
• Fludarabine
• Stem Cell Transplant

Trial Overview The study tests if emapalumab alone or in combination with fludarabine and dexamethasone can reduce inflammation effectively before a stem cell transplant in patients with PIRD/autoinflammatory conditions. It aims to improve the engraftment success of the transplant.

How Is the Trial Designed?

Group I: Group B: Fludarabine and Dexamethasone (for generalized autoinflammation) Experimental Treatment 2 Interventions

Participants in this group will receive fludarabine and dexamethasone for 5 days in a row on Days -22 through -18.

Group II: Group A: Emapalumab (for isolated Interferongamma mediated disease) Experimental Treatment 2 Interventions

Participants in this group will receive emapalumab on Days -22 (22 days before the day of the stem cell transplant), -15, -8, and -1.

Dexamethasone is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Dexamethasone for:

• Inflammation
• Allergic reactions
• Respiratory diseases
• Skin conditions
• Eye diseases
• Immune system disorders

Approved in United States as Dexamethasone for:

• Inflammatory conditions
• Allergic states
• Respiratory diseases
• Blood disorders
• Neoplastic diseases
• Nervous system disorders

Approved in Canada as Dexamethasone for:

• Inflammation
• Allergic reactions
• Respiratory diseases
• Skin conditions
• Eye diseases

Approved in Japan as Dexamethasone for:

• Inflammatory conditions
• Allergic states
• Respiratory diseases
• Blood disorders

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Sobi, Inc.

Industry Sponsor

Trials

14

Recruited

1,000+

Published Research Related to This Trial

Immunosuppressive drugs have significantly improved the survival rates of patients receiving solid organ transplants by effectively blocking lymphocyte activity, with current treatments primarily based on calcineurin inhibitors like cyclosporine and tacrolimus.

The review highlights the importance of understanding the mechanisms, therapeutic uses, and potential adverse effects of these drugs, while also addressing challenges in managing immunosuppression for transplant recipients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunosuppressive agents in transplantation: mechanisms of action and current anti-rejection strategies. Gorantla, VS., Barker, JH., Jones, JW., et al.[2019]

Corticosteroids are commonly used as the first-line treatment for systemic autoimmune diseases, but their long-term use can lead to significant side effects, especially as the dose and duration increase.

To mitigate these side effects, strategies such as combining corticosteroids with immunosuppressants or immunomodulatory agents are recommended, with the choice of treatment tailored to the specific disease and its underlying mechanisms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Benefits and risks of treatments used in systemic autoimmune diseases]. Mouthon, L.[2016]

The fluorinated analog of the steroidal antedrug showed twice the potency in reducing inflammation compared to the original compound, indicating enhanced local anti-inflammatory activity.

Importantly, the new fluorinated compound did not increase systemic side effects, which is likely due to its unique chemical structure that limits adverse effects while maintaining efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel fluorinated antiinflammatory steroid with reduced side effects: methyl 9 alpha-fluoroprednisolone-16-carboxylate. McLean, HM., Khalil, MA., Heiman, AS., et al.[2019]

Mofetil microphenolate (MM) is a novel immunosuppressant that shows comparable efficacy to the conventional anti-SLE drug cyclophosphamide, which is known to have poorer tolerance.

The review highlights the potential of MM as a safer alternative for treating systemic lupus erythematosus (SLE), addressing current pharmacotherapy challenges.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[New trends in chemotherapy of systemic lupus erythematosus: treatment with mycophenolate mofetil]. Shekshina, SV., Kliukvina, NG., Nasonov, EL., et al.[2016]

High-dose oral prednisone (1mg/kg/day) is the primary treatment for polymyositis/dermatomyositis (PM/DM), and its dosage should be gradually reduced based on how well the patient responds.

For patients who do not respond to prednisone, methotrexate or azathioprine are recommended as first-line immunosuppressive therapies, while TNF-α antagonists are not advised due to safety and efficacy concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapy of polymyositis and dermatomyositis. Marie, I.[2016]

In a study involving rabbits, fluorometholone was found to be as effective as dexamethasone phosphate and prednisolone acetate in preventing immune rejection of corneal grafts, with only one rejection in each treatment group compared to eight in the control group.

The results suggest that fluorometholone can be a viable alternative to other corticosteroids for preventing corneal graft rejection, as confirmed by histological examination of the grafts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prevention of immune graft rejection after corneal transplantation. Fleming, JC., Reid, FR., Wood, TO.[2021]

Immunosuppressive drugs like corticosteroids, azathioprine, cyclophosphamide, cyclosporine, and anti-CD3 monoclonal antibodies work by targeting different aspects of the immune response, with corticosteroids primarily redistributing lymphocytes and reducing inflammation.

These drugs are used effectively in treating conditions such as renal disease, systemic vasculitis, and connective tissue diseases, highlighting their importance in managing autoimmune and inflammatory disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunosuppressive drugs in clinical medicine. ten Berge, RJ., Schellekens, PT.[2005]

Immunosuppressive agents, while effective, carry significant risks such as increased susceptibility to infections and malignancies, with specific side effects varying by drug class; for example, corticosteroids can lead to osteoporosis and gastrointestinal issues, while cytotoxic agents like azathioprine and methotrexate primarily cause bone marrow suppression.

Cyclosporine is associated with acute and chronic nephrotoxicity, especially when combined with ketoconazole, highlighting the importance of monitoring drug interactions and plasma levels to prevent severe kidney damage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Immunosuppression--a tightrope walk between iatrogenic harm and therapy]. Berchtold, P., Seitz, M.[2013]

Glucocorticoids are essential for treating rheumatoid arthritis due to their strong anti-inflammatory and immunosuppressive effects, but they can also cause adverse effects, highlighting the need for safer usage strategies.

The novel delayed-release (DR) prednisone formulation has been shown to improve the benefit-risk ratio of glucocorticoid treatment, and it has recently been approved in the U.S. for various rheumatologic and respiratory conditions, following positive results from the CAPRA studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A fresh look at glucocorticoids how to use an old ally more effectively. Buttgereit, F.[2013]

Immunosuppressive regimens for organ transplants have evolved significantly since the first transplant in 1954, utilizing a combination of drugs with different mechanisms to enhance efficacy while reducing side effects.

The article reviews various classes of immunosuppressants, including glucocorticoids and mTOR inhibitors, highlighting their actions and potential side effects, and discusses future advancements in immunosuppressive therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An Overview of Transplant Immunosuppression--History, Principles, and Current Practices in Kidney Transplantation. Colaneri, J.[2021]

In a 26-week double-blind trial involving 20 patients with Crohn's disease, azathioprine significantly reduced the number of relapses compared to placebo, with only 2 relapses in the azathioprine group versus 7 in the placebo group.

Patients taking azathioprine were able to reduce their steroid dosage more effectively than those on placebo, suggesting that azathioprine may help manage Crohn's disease symptoms while allowing for lower steroid use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A controlled trial of azathioprine in Crohn's disease. Rosenberg, JL., Levin, B., Wall, AJ., et al.[2020]

Glucocorticoids, particularly high-dose prednisone, are essential for treating pediatric systemic lupus erythematosus (SLE), especially in cases of diffuse proliferative glomerulonephritis (DPGN), where azathioprine is recommended at diagnosis.

Hydroxychloroquine is suggested for routine use in all SLE cases, while methotrexate shows promise with a good safety profile, indicating a need for further research on its efficacy in children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An overview of the treatment of childhood SLE. Silverman, ED., Lang, B.[2019]

In a 22-month study involving 31 patients with essential mixed cryoglobulinemia, both deflazacort (DF) and prednisone (PD) significantly improved symptoms like joint pain and skin purpura within 15 days, with effects maintained throughout the study.

Deflazacort demonstrated more intense and prolonged immunological effects compared to prednisone, with better tolerance and fewer side effects related to glucose and body weight, suggesting it may be a preferable option for treating this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deflazacort versus Prednisone in the Treatment of Essential Mixed Cryoglobulinemia A Between-Patient Controlled Clinical Study. Vacca, A., Dammacco, F.[2021]

Low doses of prednisone or prednisolone (10 mg daily or 5 mg twice daily) effectively control inflammation and slow bone damage in early polyarticular rheumatoid arthritis, making them original disease-modifying antirheumatic drugs.

These glucocorticoids provide stronger anti-inflammatory effects with fewer side effects compared to NSAIDs or COX-2 inhibitors, and their use can be safely managed with calcium and vitamin D supplementation to minimize the risk of osteopenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Resolved: Low-dose prednisone is indicated as a standard treatment in patients with rheumatoid arthritis. Conn, DL.[2019]

Citations

1. gamifant.com gamifant.com/phlh/results

Primary HLH efficacy data Review the efficacy data for Gamifant, including overall response rate and percentage of patients who proceeded to HSCT.

2. gamifantcares.com gamifantcares.com/studyresults

About Gamifant® (emapalumab-lzsg) | Study results GAMIFANT affects your immune system and may lower the ability of your immune system to fight infections. Gamifant may increase your risk of serious ...

3. sobi.com sobi.com/en/press-releases/fda-approves-gamifantr-emapalumab-lzsg-first-ever-treatment-adults-and-children-macrophage-activation-syndrome-stills-disease-2342991

FDA approves Gamifant® (emapalumab-lzsg) as first-ever ... Approval based on the pooled analysis of our pivotal EMERALD and NI-0501-06 studies, showing 54% of patients treated with Gamifant achieved ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11117018/

Real-world treatment patterns and outcomes in patients with ... Key Points. •. Addition of emapalumab improves laboratory parameters and overall survival in patients with pHLH in real-world clinical practice.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11111609/

Population Pharmacokinetics of the Anti-Interferon-Gamma ... The efficacy and safety of emapalumab has been demonstrated in patients with both primary HLH and MAS in sJIA [14, 15]. Prior population ...

6. gamifant.com gamifant.com/phlh/safety

Safety Data | Gamifant® (emapalumab-lzsg) For HCPs Serious adverse reactions were reported in 53% of patients. The most common serious adverse reactions (≥3%) included infections, gastrointestinal hemorrhage ...

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2018/761107lbl.pdf

GAMIFANT (emapalumab-lzsg) injection, - accessdata.fda.gov The safety data described in this section reflect exposure to GAMIFANT in which 34 patients ... immune system and may lower the ability of your immune system.

8. gamifantcares.com gamifantcares.com/safety

What should I know about the side effects of Gamifant? Risk of serious infections. Because Gamifant affects the immune system, it may lower a patient's ability to fight infections. Gamifant may increase the risk of ...

9. gamifant.com gamifant.com/sites/default/files/2025-07/Full-Prescribing-Information.pdf

Full prescribing Information Safety and effectiveness of GAMIFANT have been established in pediatric patients, newborn and older, with primary HLH that is reactivated or refractory to ...

10. uhcprovider.com uhcprovider.com/content/dam/provider/docs/public/policies/comm-medical-drug/gamifant-emapalumab-lzsg.pdf

Gamifant® (Emapalumab-Lzsg) Study NI-0501-05, was a multicenter follow-up study to collect safety and outcome data for patients who received emapalumab through NI-0501-04 and compassionate ...