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

23 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This is an open-label, single-group, Phase I/II study of itacitinib in combination with everolimus in subjects with relapsed or refractory classical Hodgkin lymphoma (cHL).

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 the combination of Itacitinib and Everolimus safe for humans?

Everolimus, also known as Afinitor, has been used in treating advanced renal cell carcinoma and is generally well tolerated. Most side effects are mild to moderate, such as mouth sores, tiredness, lung inflammation, and infections. ^{1 2 3 4 5}

How is the drug Itacitinib + Everolimus unique for treating Hodgkin Lymphoma?

The combination of Itacitinib and Everolimus is unique because it targets specific pathways involved in cancer cell growth and survival, potentially offering a new approach for patients with relapsed or refractory Hodgkin Lymphoma who have not responded to other treatments. This combination leverages the effects of mTOR inhibitors like Everolimus, which have shown promise in other lymphoma treatments, and adds the novel action of Itacitinib, which may enhance the overall effectiveness. ^{6 7 8 9 10}

What data supports the effectiveness of the drug combination Itacitinib and Everolimus for treating Hodgkin Lymphoma?

Everolimus has shown effectiveness in treating various types of lymphoma, including relapsed indolent lymphoma, with a 35% overall response rate in a clinical trial. This suggests potential benefits when combined with Itacitinib for Hodgkin Lymphoma. ^{1 5 6 11 12}

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

Phase I study of panobinostat plus everolimus in patients with relapsed or refractory lymphoma. [2021]

2. New Zealand pubmed.ncbi.nlm.nih.gov

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

3. Germany pubmed.ncbi.nlm.nih.gov

Everolimus and PTK/ZK show synergistic growth inhibition in the orthotopic BL16/BL6 murine melanoma model. [2021]

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

Efficacy of the oral mTORC1 inhibitor everolimus in relapsed or refractory indolent lymphoma. [2021]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Use of dual mTOR inhibitor MLN0128 against everolimus-resistant breast cancer. [2022]

6. Spain pubmed.ncbi.nlm.nih.gov

Everolimus in renal cell carcinoma. [2021]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Everolimus - a new approach in the treatment of renal cell carcinoma. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Everolimus for the treatment of advanced renal cell carcinoma. [2021]

9. Italy pubmed.ncbi.nlm.nih.gov

ENGAGE- 501: phase II study of entinostat (SNDX-275) in relapsed and refractory Hodgkin lymphoma. [2018]

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

Safety and Efficacy of Vorinostat Plus Sirolimus or Everolimus in Patients with Relapsed Refractory Hodgkin Lymphoma. [2021]

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

A phase 2 study of vorinostat for treatment of relapsed or refractory Hodgkin lymphoma: Southwest Oncology Group Study S0517. [2021]

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

DTRMWXHS-12, a novel Bruton tyrosine kinase inhibitor, in combination with everolimus and pomalidomide in patients with relapsed/refractory lymphomas: An open-label, multicenter, phase 1a/1b study. [2023]