Itacitinib for Graft-versus-Host Disease

Overseen By Uday R Popat, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Anti-arrhythmics

Disqualifiers: Acute leukemia, Cardiac disease, Hepatitis, 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 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 101

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether adding itacitinib, a JAK inhibitor, to the usual treatment can help prevent graft-versus-host disease (GVHD) in individuals who have received a donor stem cell transplant. GVHD occurs when donor cells attack the recipient's body cells. The trial targets patients with blood disorders who are about to undergo a specific type of stem cell transplant from a matched donor. It suits those who have undergone or will undergo this transplant and seek to prevent GVHD. As a Phase 2 trial, this research measures 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 if you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

Is there any evidence suggesting that itacitinib is likely to be safe for humans?

Research has shown that itacitinib is safe for humans. In an earlier study, itacitinib did not harm the process where transplanted cells grow and produce healthy blood cells. Another study found that patients did not experience severe cases of cytokine release syndrome (CRS), an immune system overreaction. Most patients had no CRS or only mild symptoms. These findings indicate that itacitinib is generally well-tolerated, with few serious side effects, suggesting its safety for patients treated for graft-versus-host disease. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for GVHD?

Most treatments for graft-versus-host disease (GVHD), like corticosteroids, work by broadly suppressing the immune system. But itacitinib stands out because it specifically targets the JAK1 pathway, which plays a key role in the inflammatory process of GVHD. This targeted approach might reduce the unwanted side effects often seen with generalized immune suppression. Researchers are excited because itacitinib could offer a more precise treatment option, potentially improving patient outcomes while minimizing complications.

What evidence suggests that itacitinib might be an effective treatment for graft-versus-host disease?

Research has shown that itacitinib, which participants in this trial will receive as part of supportive care, can help prevent graft-versus-host disease (GVHD). This condition occurs when the donor's cells attack the patient's body after a stem cell transplant. Earlier studies found that itacitinib effectively stopped severe GVHD without increasing the risk of transplant failure. More patients responded positively to itacitinib within just 7 days compared to other treatments, and these positive results continued at 28 days. Long-term results for itacitinib were similar to traditional treatments like corticosteroids, and itacitinib was also found to be safe. These studies suggest that itacitinib could be a promising option for reducing the risk of GVHD after transplants. ^{1 4 6 7 8}

Who Is on the Research Team?

Uday R. Popat

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults aged 18-70 with blood disorders who are undergoing a stem cell transplant from a donor. They must have good organ function, agree to use contraception, and not be pregnant. People with serious heart conditions, active hepatitis B or C, or unresolved treatment side effects can't join.

Inclusion Criteria

Direct bilirubin not greater than 1 mg/dL

DLCO 50% of predicted corrected for hemoglobin

Life expectancy of at least 12 weeks

Exclusion Criteria

Active hepatitis B and C

My leukemia is in the first complete remission or chronic phase.

I still have side effects from previous treatments that are noticeable.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Conditioning

Patients receive busulfan, thiotepa, and fludarabine as part of the conditioning regimen before stem cell transplant

17 days

Multiple visits for IV administration

Stem Cell Transplant

Patients undergo stem cell transplant

1 day

1 visit (in-person)

GVHD Prophylaxis

Patients receive cyclophosphamide, itacitinib, and tacrolimus to prevent graft-versus-host disease

56 days

Regular visits for monitoring and medication administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

365 days

Follow-up visits at days 100, 180, and 365

What Are the Treatments Tested in This Trial?

Interventions

• Itacitinib

Trial Overview The study is testing if adding Itacitinib to standard treatments (Cyclophosphamide, Tacrolimus) after a stem cell transplant can prevent graft-versus-host disease—a condition where donor cells attack the patient's body.

How Is the Trial Designed?

Group I: Supportive care (itacitinib) Experimental Treatment 7 Interventions

CONDITIONING: Patients receive busulfan IV over 3 hours on days -20, -13, and -6 to -3, thiotepa IV on day -7, and fludarabine IV over 1 hour on days -6 to -3. STEM CELL TRANSPLANT: Patients undergo stem cell transplant on day 0. GVHD PROPHYLAXIS: Patients receive cyclophosphamide IV over 3 hours on days 3 and 4. Patients also receive itacitinib PO QD on days 5-60 in the absence of disease progression or unacceptable toxicity. Beginning day 5 after stem cell transplant, patients also receive tacrolimus IV over 24 hours until able to tolerate oral tacrolimus, whereby patients then receive tacrolimus PO BID.

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Incyte Corporation

Industry Sponsor

Trials

408

Recruited

66,800+

Steven Stein

Incyte Corporation

Chief Medical Officer since 2015

MD from University of Witwatersrand

Hervé Hoppenot

Incyte Corporation

Chief Executive Officer since 2014

MBA from ESSEC Business School

Published Research Related to This Trial

In a phase 3 study involving 439 patients with acute graft-versus-host disease (GVHD), the Janus kinase 1 inhibitor itacitinib showed a higher overall response rate (ORR) of 74% compared to 66% for placebo when combined with corticosteroids, although this difference did not reach statistical significance.

Both treatment groups experienced a high rate of grade 3 or worse adverse events, with similar safety profiles, indicating that while itacitinib may improve response rates, its safety is comparable to standard treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of itacitinib versus placebo in combination with corticosteroids for initial treatment of acute graft-versus-host disease (GRAVITAS-301): a randomised, multicentre, double-blind, phase 3 trial. Zeiser, R., Socié, G., Schroeder, MA., et al.[2022]

In a study of 8 patients with severe sclerotic chronic graft-vs-host disease (scGVHD), dasatinib showed a higher response rate of 60% compared to 25% for imatinib, indicating it may be a more effective treatment option.

Dasatinib was better tolerated and had a lower incidence of serious side effects, making it a safer and steroid-sparing alternative for patients who are refractory to imatinib.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Imatinib and dasatinib as salvage therapy for sclerotic chronic graft-vs-host disease. Sánchez-Ortega, I., Parody, R., Servitje, O., et al.[2019]

Itacitinib, a selective JAK1 inhibitor, was well tolerated in a phase 1 study involving 29 patients with acute graft-versus-host disease (aGVHD), showing a promising overall response rate of 78.6% for the 200 mg dose and 66.7% for the 300 mg dose by day 28.

The study indicated that itacitinib could reduce the need for corticosteroids over time, suggesting its potential as an effective treatment option for both steroid-naive and steroid-refractory aGVHD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 1 trial of itacitinib, a selective JAK1 inhibitor, in patients with acute graft-versus-host disease. Schroeder, MA., Khoury, HJ., Jagasia, M., et al.[2021]

Citations

1. ashpublications.org ashpublications.org/blood/article/145/13/1382/526136/Itacitinib-for-prevention-of-graft-versus-host

Itacitinib for prevention of graft-versus-host disease and ... Itacitinib was extremely effective at preventing grade 2 to 4 CRS and grade 3/4 aGVHD, with no clear increase in relapse rate. Itacitinib was ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36095841/

Effective treatment of low-risk acute GVHD with itacitinib ... More patients responded to itacitinib within 7 days (81% vs 66%, P = .02), and response rates at day 28 were very high for both groups (89% vs ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04127721?term=Graft-versus-Host%20Disease%20and%20stem%20cells&viewType=Table&rank=6

Itacitinib for the Prevention of Graft Versus Host Disease in ... This phase II trial studies how well itacitinib works in preventing graft versus host disease in patients with blood disorders undergoing donor stem cell ...

4. healio.com healio.com/news/hematology-oncology/20230209/itacitinib-appears-effective-for-acute-graft-versus-host-disease

Itacitinib appears effective for acute graft-versus-host disease Long-term outcomes appeared comparable between itacitinib and systemic corticosteroids, with similar risk for chronic GVHD, findings presented ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04446182

Itacitinib (INCB039110) and Extracorporeal Photopheresis ... Participants were assessed for chronic graft versus host disease (GVHD) severity per the NIH Consensus Development Project Criteria at baseline, after 24 weeks ...

6. investor.incyte.com investor.incyte.com/news-releases/news-release-details/incyte-announces-results-phase-3-study-itacitinib-patients

Incyte Announces Results of Phase 3 Study of Itacitinib in ... GRAVITAS-301 results show that treatment with itacitinib in combination with corticosteroids did not statistically improve overall response rate or non-relapse ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/34971577/

Efficacy and safety of itacitinib versus placebo in ... We aimed to evaluate the Janus kinase 1 inhibitor itacitinib versus placebo, both in combination with corticosteroids, for initial treatment of acute GVHD.

8. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006497124111032

Itacitinib for prevention of graft-versus-host disease and ... Itacitinib resulted in low CRS grades, all patients had grade 0 (22%) or grade 1 (78%) CRS and there were no cases of grade 2 to 5 CRS. There ...