Itacitinib for Graft-versus-Host Disease

Overseen By Uday R Popat, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

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)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 101

31 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II trial studies if itacitinib plus standard of care treatment may help prevent graft-versus-host-disease (GVHD) in patients who have received an allogeneic (donor) stem cell transplant. An allogeneic transplant uses blood-making cells from a family member or unrelated donor to remove and replace a patient's abnormal blood cells. Sometimes the transplanted cells from a donor can attack the body's normal cells (called graft-versus-host disease). Giving itacitinib with standard of care treatment after the transplant may stop this from happening.

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.

What data supports the effectiveness of the drug Itacitinib for treating graft-versus-host disease?

Research shows that Itacitinib, a selective JAK1 inhibitor, is effective in treating acute graft-versus-host disease (GVHD). In a study, patients with low-risk GVHD treated with Itacitinib had a high response rate and fewer serious infections compared to those treated with standard corticosteroids. Additionally, Itacitinib was well tolerated and reduced the need for corticosteroids in patients with steroid-naive or steroid-refractory acute GVHD. ^{1 2 3 4 5}

Is itacitinib safe for humans?

Itacitinib has been generally well tolerated in clinical trials for graft-versus-host disease, with common side effects including diarrhea and anemia. Serious infections were less common in patients treated with itacitinib compared to those on standard corticosteroids, and no severe adverse events occurred in more than 10% of patients. ^{4 5 6 7 8}

How does the drug itacitinib differ from other treatments for graft-versus-host disease?

Itacitinib is unique because it is a selective JAK1 inhibitor, which means it specifically targets a part of the immune system involved in graft-versus-host disease, potentially reducing the need for high-dose steroids. This drug has shown promise in treating both steroid-naive and steroid-refractory cases, and it may lead to fewer serious infections compared to traditional steroid treatments. ^{4 5 6 7 9}

Research Team

Uday R. Popat

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

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

I can speak English or another language.

Exclusion Criteria

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

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

My donor for the transplant is a half-match and I have antibodies against their cells.

Timeline

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

References

1. Croatia pubmed.ncbi.nlm.nih.gov

Imatinib and dasatinib as salvage therapy for sclerotic chronic graft-vs-host disease. [2019]

2. England pubmed.ncbi.nlm.nih.gov

A biomarker signature to predict complete response to itacitinib and corticosteroids in acute graft-versus-host disease. [2023]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Targeting Interleukin-2-Inducible T-Cell Kinase (ITK) Differentiates GVL and GVHD in Allo-HSCT. [2022]

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

Effective treatment of low-risk acute GVHD with itacitinib monotherapy. [2023]

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

A phase 1 trial of itacitinib, a selective JAK1 inhibitor, in patients with acute graft-versus-host disease. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Effect of Itraconazole or Rifampin on Itacitinib Pharmacokinetics When Administered Orally in Healthy Subjects. [2020]

7. England pubmed.ncbi.nlm.nih.gov

Itacitinib Population Pharmacokinetics and Exposure-Response in Patients With Acute Graft-Versus-Host Disease. [2023]

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

Pretransplant Short-Term Exposure of Donor Graft Cells to ITK Selective Inhibitor Ameliorates Acute Graft-versus-Host Disease by Inhibiting Effector T Cell Differentiation while Sparing Regulatory T Cells. [2022]

9. England 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. [2022]