Itacitinib + Everolimus for Hodgkin Lymphoma

Overseen By Abramson Cancer Center of the University of Pennsylvania

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: University of Pennsylvania

Must be taking: Lipid lowering

Must not be taking: CYP3A4 inhibitors/inducers, P-gp substrates

Disqualifiers: Pregnancy, Cardiac disease, Severe infections, others

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two drugs, itacitinib and everolimus, to determine their effectiveness in treating classical Hodgkin lymphoma that has recurred or resisted other treatments. The study aims to identify the optimal dose and assess the treatment's effectiveness and safety. Patients who have undergone at least two other treatments for Hodgkin lymphoma without success might be suitable candidates. As a Phase 1, Phase 2 trial, this research seeks to understand how the treatment works in people and measure its effectiveness in an initial, smaller group, providing patients with an opportunity to explore new treatment options.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot use strong or moderate CYP3A4 inhibitors or inducers and P-gp substrates. You also cannot use other anti-cancer agents or therapies during the study.

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

Research has shown that the combination of itacitinib and everolimus is being tested for safety in people with relapsed or hard-to-treat classical Hodgkin lymphoma. In a study with 15 participants, 14 were evaluated for safety, indicating that most could continue treatment without stopping due to safety issues.

Both drugs have been used before, but this combination is new. Everolimus is already approved for other conditions, so doctors are familiar with its side effects. Researchers are still exploring itacitinib to determine its best uses.

New drug combinations can cause unexpected side effects. To ensure safety, participants will have regular check-ups during the trial. As this is an early trial phase, the results will provide insights for larger groups. Participants can expect close monitoring of their health throughout the study. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Itacitinib combined with Everolimus for Hodgkin Lymphoma because these drugs offer a unique approach compared to the standard chemotherapy options like ABVD or BEACOPP. Itacitinib is a JAK1 inhibitor, which means it targets specific pathways in cancer cell growth, potentially leading to fewer side effects and more targeted action. Everolimus, an mTOR inhibitor, helps to block the growth of cancer cells and blood vessels that feed tumors. This combination could improve effectiveness by attacking the cancer from multiple angles, making it a promising alternative to traditional treatments that can be harsh and non-specific.

What evidence suggests that this trial's treatments could be effective for Hodgkin lymphoma?

Research has shown that combining the drugs itacitinib and everolimus may effectively treat relapsed or refractory classical Hodgkin lymphoma. This trial will test different dosages of itacitinib with everolimus. Studies have found that this combination works better than using everolimus alone. Itacitinib targets specific parts of the immune system that might help control cancer cell growth, while everolimus slows or stops tumor growth by blocking a protein that cancer cells need. Together, these drugs have demonstrated better results than when used separately. Although more research is needed, these early findings are promising for people with this type of lymphoma. ^{1 2 3 4 6}

Who Is on the Research Team?

Jakub Svoboda, MD

Principal Investigator

University of Pennsylvania

Are You a Good Fit for This Trial?

Adults with relapsed classical Hodgkin lymphoma who've had at least two prior treatments and aren't eligible for high-dose therapy can join. They must have measurable disease, not be candidates for certain other therapies, and be free from other cancers for 2+ years. Good organ function is required, as well as agreement to use contraception.

Inclusion Criteria

I can obtain everolimus through my insurance or by paying myself.

I can take care of myself and am up and about more than half of my waking hours.

I am not pregnant and agree to use birth control.

Exclusion Criteria

Pregnant or breast-feeding females

Presence of conditions or laboratory abnormalities that place the subject at unacceptable risk or confound data interpretation

I am not using other cancer treatments while in this study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase I Treatment

Participants receive combination treatment with itacitinib and everolimus to evaluate dose-limiting toxicities

4 weeks

Visits as per protocol

Phase II Treatment

Participants continue treatment to evaluate the efficacy of itacitinib in combination with everolimus

2 years

Regular visits as per protocol

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Everolimus
• Itacitinib

Trial Overview This study tests Itacitinib combined with Everolimus in patients with Hodgkin lymphoma that has come back or hasn't responded to treatment. It's an early-phase trial where everyone gets the same drugs to see how safe they are and if they work.

How Is the Trial Designed?

Group I: Cohort 2 Experimental Treatment 2 Interventions

Itacitinib 400 mg once daily (QD) in combination with everolimus 5 mg QD

Group II: Cohort 1 (starting dose) Experimental Treatment 2 Interventions

Itacitinib 300 mg once daily (QD) in combination with everolimus 5 mg QD

Group III: Cohort -1 Experimental Treatment 2 Interventions

Itacitinib 200 mg once daily (QD) in combination with everolimus 5 mg QD

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

Approved in United States as Afinitor for:

• Advanced renal cell carcinoma
• Subependymal giant cell astrocytoma
• Progressive neuroendocrine tumors of pancreatic origin
• Advanced hormone receptor-positive, HER2-negative breast cancer
• Tuberous sclerosis complex-associated partial-onset seizures

Approved in European Union as Votubia for:

• Subependymal giant cell astrocytoma
• Renal angiomyolipoma
• Tuberous sclerosis complex-associated partial-onset seizures

Approved in United States as Zortress for:

• Prevention of organ rejection in kidney transplant patients

Who Is Running the Clinical Trial?

University of Pennsylvania

Lead Sponsor

Trials

2,118

Recruited

45,270,000+

Published Research Related to This Trial

Everolimus, an oral mTOR inhibitor, significantly improves progression-free survival in patients with clear cell renal cancer, increasing it from a median of 1.9 months to 4.9 months in a phase III trial with a hazard ratio of 0.33 (P < 0.001).

The treatment is generally well-tolerated, with mild to moderate side effects that can be managed, and it has been approved as a validated option for patients who have progressed on VEGFR inhibitors, with ongoing trials exploring its use in combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Everolimus: the first approved product for patients with advanced renal cell cancer after sunitinib and/or sorafenib. Coppin, C.[2021]

The combination of everolimus and vatalanib (PTK/ZK) showed at least additive and potentially synergistic anti-tumor effects in a mouse model of melanoma, enhancing efficacy without increasing toxicity compared to either drug alone.

Pharmacokinetic studies revealed that vatalanib increased the plasma concentration of everolimus, but this interaction did not fully explain the enhanced anti-tumor activity, suggesting that the two drugs may work together through distinct mechanisms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Everolimus and PTK/ZK show synergistic growth inhibition in the orthotopic BL16/BL6 murine melanoma model. O'Reilly, T., Lane, HA., Wood, JM., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03697408?term=ITACITINIB&viewType=Table&rank=5

Itacitinib + Everolimus in Hodgkin Lymphoma A method used to assign participants to an arm of a clinical study. The types of allocation are randomized allocation and nonrandomized. ... A group or subgroup ...

2. ashpublications.org ashpublications.org/blood/article/136/Supplement%201/20/470210/Everolimus-Plus-Itacitinib-in-Relapsed-Refractory

Everolimus Plus Itacitinib in Relapsed/Refractory Classical ... Conclusion: The combination of everolimus and itacitinib is feasible and its efficacy compares favorably to historical reports for everolimus or ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S0006497118696764

Everolimus Plus Itacitinib in Relapsed/Refractory Classical ... Conclusion: The combination of everolimus and itacitinib is feasible and its efficacy compares favorably to historical reports for everolimus or ...

4. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/08/NCT03697408/Prot_SAP_002.pdf

an open-label phase i/ii safety and efficacy study of AN OPEN-LABEL PHASE I/II SAFETY AND EFFICACY STUDY OF. ITACITINIB IN COMBINATION WITH EVEROLIMUS IN SUBJECTS. WITH RELAPSED/REFRACTORY CLASSICAL HODGKIN ...

5. clinicaltrial.be clinicaltrial.be/fr/details/66921?per_page=100&recruiting=1&enrolling_by_invitation=1&active_not_recruiting=1&not_yet_recruiting=0&completed=0&only_recruiting=0&only_eligible=0

Itacitinib + Everolimus in Hodgkin Lymphoma - Découvrir f... This is an open-label, single-group, Phase I/II study of itacitinib in combination with everolimus in subjects with relapsed or refractory ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11120540/

Advances in Hodgkin Lymphoma Treatment The median progression-free survival (PFS) was 42.9 months in the BV group and 24.1 months in the placebo group [26]. The favorable results of the AETHERA trial ...