Itacitinib for Blood Cancer

Overseen By Ivana Gojo, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Disqualifiers: Active leukemia, CNS malignancy, HIV, 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: Unknown

Duration: 13 weeks

32 Participants Needed

Trial Summary

What is the purpose of this trial?

This research is being done to learn whether drug called itacitinib, which is a novel inflammation- and immune-lowering drug (immunosuppressant), can be given before and after non-myeloablative peripheral blood stem cell transplantation (PBSCT; also known as a 'mini' transplant) to help prevent certain complications such as cytokine release syndrome (CRS) for patients with blood cancers, using peripheral blood from a relative. The investigators will also examine if by using itacitinib the investigators can reduce the duration of MMF (other immune suppressive drug administration posttransplant).

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.

What makes the drug Itacitinib unique for treating blood cancer?

Itacitinib is unique because it is a selective JAK1 inhibitor, which means it specifically targets and blocks the activity of the Janus kinase 1 enzyme involved in immune responses. This selectivity may offer a more targeted approach with potentially fewer side effects compared to broader treatments. ^{1 2 3 4 5}

Research Team

Ivana Gojo, MD

Principal Investigator

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Eligibility Criteria

This trial is for older patients (60+) with various blood cancers like leukemia, myelodysplastic syndrome, and multiple myeloma. They must be in remission or have responded to treatment and have a partially matched related stem cell donor. Key requirements include good heart and liver function, adequate breathing capacity, and an acceptable level of physical fitness.

Inclusion Criteria

I have a family member who can donate stem cells to me.

You are eligible if you have certain types of leukemia, myelodysplastic syndrome, myeloproliferative disease, or multiple myeloma and meet specific age and organ function requirements.

Exclusion Criteria

I do not have HIV.

I have not had a bone marrow transplant from another person.

Not pregnant or breast-feeding

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Itacitinib is administered at 200 mg orally daily from day -3 to day 90 in conjunction with one of four different regimens for immunosuppression

13 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of CRS and GVHD

4 weeks

Extension

Itacitinib may continue beyond day +90 if there is GVHD

Treatment Details

Interventions

• Itacitinib

Trial Overview Researchers are testing Itacitinib as an immunosuppressant before and after 'mini' stem cell transplants from relatives to prevent complications like cytokine release syndrome in blood cancer patients. The study also aims to see if it can shorten the need for other immune suppressive drugs post-transplant.

Participant Groups

Group I: Itacitinib Experimental Treatment 1 Intervention

Itacitinib will be given at 200 mg orally daily from day -3 to day 90. Itacitinib will be given in conjunction with one of four different regimens for immunosuppression. These 4 regimens are listed in Table 2, Section 5.2 of the protocol. Itacitinib may continue beyond day +90 if there is GVHD. NOTE: If patient develops GVHD requiring treatment after all immune suppression, including itacitinib, is stopped on day +90, the itacitinib will not be restarted and the patient will be treated per standard of care.

Itacitinib is already approved in European Union, United States for the following indications:

Approved in European Union as Itacitinib for:

• Graft-versus-host disease

Approved in United States as Itacitinib for:

• Graft-versus-host disease

Who Is Running the Clinical Trial?

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Lead Sponsor

Trials

578

Recruited

33,600+

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 phase 2 trial involving 124 women with untreated triple-negative breast cancer, the addition of the AKT inhibitor ipatasertib to paclitaxel significantly improved median progression-free survival to 6.2 months compared to 4.9 months with placebo, indicating its potential efficacy in this patient population.

Ipatasertib was associated with some adverse events, notably diarrhea in 23% of patients, but no severe treatment-related complications or deaths were reported, suggesting a manageable safety profile for further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ipatasertib plus paclitaxel versus placebo plus paclitaxel as first-line therapy for metastatic triple-negative breast cancer (LOTUS): a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial. Kim, SB., Dent, R., Im, SA., et al.[2022]

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 participants with moderate hepatic impairment, itacitinib showed a 2.5-fold increase in total drug exposure and a 2-fold increase in peak concentration compared to those with normal liver function, indicating that liver health significantly affects the drug's metabolism.

For those with severe hepatic impairment, the increases were even more pronounced, with a 4-fold increase in total exposure and a 3.5-fold increase in peak concentration, suggesting careful dosing adjustments may be necessary for patients with liver issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Hepatic Impairment on the Pharmacokinetics of Itacitinib. Barbour, AM., Rockich, K., Cimino, E., et al.[2021]

In a phase 3 study involving 36 healthy participants, itacitinib, a JAK1-selective inhibitor, showed no significant impact on cardiac safety, with no clinically meaningful effects on QTc intervals, even at high plasma concentrations up to approximately 13,000 nM.

The analysis indicated that itacitinib does not cause a QTc effect exceeding the safety threshold of 10 milliseconds, suggesting it is safe for cardiac conduction at therapeutic doses, including in patients with liver impairment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of Clinical Cardiac Safety of Itacitinib, a JAK1 Inhibitor, in Healthy Participants. Gong, X., Darpo, B., Xue, H., et al.[2021]

Birinapant, a drug that targets inhibitors of apoptosis proteins (IAPs), shows promise as a treatment for triple-negative breast cancer (TNBC) by enhancing the effectiveness of gemcitabine, a commonly used chemotherapy drug.

In both laboratory and mouse models, birinapant was found to activate the intrinsic apoptosis pathway, leading to increased cancer cell death when used alongside gemcitabine, suggesting a new therapeutic strategy for patients with limited treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Birinapant Enhances Gemcitabine's Antitumor Efficacy in Triple-Negative Breast Cancer by Inducing Intrinsic Pathway-Dependent Apoptosis. Xie, X., Lee, J., Liu, H., et al.[2022]

References

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

Ipatasertib plus paclitaxel versus placebo plus paclitaxel as first-line therapy for metastatic triple-negative breast cancer (LOTUS): a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial. [2022]

2. 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]

3. England pubmed.ncbi.nlm.nih.gov

Effect of Hepatic Impairment on the Pharmacokinetics of Itacitinib. [2021]

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

Evaluation of Clinical Cardiac Safety of Itacitinib, a JAK1 Inhibitor, in Healthy Participants. [2021]

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

Birinapant Enhances Gemcitabine's Antitumor Efficacy in Triple-Negative Breast Cancer by Inducing Intrinsic Pathway-Dependent Apoptosis. [2022]