Parsaclisib Combinations for B-Cell Cancers

Not currently recruiting at 154 trial locations

Overseen By Incyte Corporation Call Center (ex-US)

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Incyte Corporation

Must be taking: Parsaclisib, Itacitinib, Ruxolitinib, Ibrutinib

Disqualifiers: Uncontrolled illness, Pregnant, 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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: Through study completion, an average of 5 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the effectiveness of parsaclisib alone or with other medications in treating B-cell cancers. It provides continued access to parsaclisib, combined with drugs like itacitinib (a JAK inhibitor), ruxolitinib (also a JAK inhibitor), or ibrutinib (known as Imbruvica, a Bruton's tyrosine kinase inhibitor) for those already benefiting from these treatments. Participants with stable disease currently in an Incyte-sponsored parsaclisib study may be suitable candidates. The trial aims to determine if these combination treatments remain effective for specific types of B-cell cancers. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, since it involves continuing treatment with specific drugs, you may need to discuss your current medications with the study team.

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

Research has shown that combining parsaclisib with drugs like ibrutinib, ruxolitinib, and itacitinib is generally safe for patients with B-cell cancers. Let's break it down:

For parsaclisib and ibrutinib, studies indicate a predictable safety profile. Most side effects are known and manageable, and this combination has been safely used with other treatments for similar conditions.

When combined with ruxolitinib, parsaclisib also shows a reassuring safety record. The combination is well-tolerated with few serious side effects, and most side effects are mild, making it manageable for patients.

For the parsaclisib and itacitinib combination, earlier studies identified doses that patients can tolerate well. Although detailed safety data is limited, findings suggest it is a promising and safe treatment pair.

Parsaclisib alone has been studied for its effects on the heart and other areas, generally showing a manageable safety profile with known and limited side effects.

Overall, these drug combinations have been tested in several studies with positive safety outcomes. While no treatment is without risks, these combinations have shown a balance of safety and effectiveness in trials so far. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for B-cell cancers because they explore unique drug combinations that might enhance effectiveness. Unlike traditional single-agent therapies, these combinations use parsaclisib, a PI3K inhibitor, alongside other targeted therapies like ibrutinib, itacitinib, and ruxolitinib. Parsaclisib specifically targets the PI3K pathway, potentially offering a more precise approach to hindering cancer cell growth. Combining it with these other drugs, which target different pathways, could offer a multi-pronged attack against cancer cells, potentially leading to better outcomes. This strategy may provide new hope for patients who have not responded well to existing treatments.

What evidence suggests that this trial's treatments could be effective for B-cell cancers?

Studies have shown that parsaclisib, a type of medication, offers promising benefits for patients with B-cell lymphomas that have returned or resisted other treatments. In this trial, participants may receive parsaclisib alone or with other drugs. Combining parsaclisib with ibrutinib, one of the study arms, may enhance effectiveness by targeting the cancer in different ways. Another arm combines parsaclisib with ruxolitinib, which has significantly reduced spleen size, a positive indicator in treating certain blood cancers. Early research suggests that adding itacitinib to parsaclisib, another combination under study, might also help by slowing cancer cell growth. Overall, these combinations aim to stop cancer cells from growing and spreading, offering hope for better patient outcomes. ^{2 3 6 7 8}

Are You a Good Fit for This Trial?

This trial is for people already in Incyte-sponsored parsaclisib studies who are tolerating treatment well, have stable B-cell malignancies, and follow study rules. They must be benefiting from current treatments with parsaclisib alone or combined with itacitinib, ruxolitinib, or ibrutinib and not pregnant nor breastfeeding.

Inclusion Criteria

I am willing and able to follow the study's schedule and treatment plans.

You are willing to prevent pregnancy or becoming a father during the study.

My condition is stable as confirmed by my doctor.

Exclusion Criteria

Participants with an uncontrolled intercurrent illness or any concurrent condition that, in the investigator's opinion, would jeopardize the safety of the participant or compliance with the Protocol

I can get parsaclisib alone or with other specific treatments outside a study.

Pregnant or breastfeeding women

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants continue treatment with parsaclisib as monotherapy or in combination with itacitinib, ruxolitinib, or ibrutinib, maintaining the same dose and schedule as in the parent Protocol

Through study completion, an average of 5 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Ibrutinib
• Itacitinib
• Parsaclisib
• Ruxolitinib

Trial Overview The Phase 2 trial provides ongoing access to the drug parsaclisib as a single agent or paired with itacitinib, ruxolitinib, or ibrutinib for participants previously enrolled in related trials. It's an open-label study meaning everyone knows what treatment they're getting.

How Is the Trial Designed?

Group I: parsaclisib + ruxolitinib Experimental Treatment 1 Intervention

Participants will continue on the same dose (1,2.5,5 OR 20 mg) and schedule of parsaclisib and the same dose of ruxolitinib that was provided in the parent Protocol at the time of the rollover.

Group II: parsaclisib + ibrutinib Experimental Treatment 1 Intervention

Participants will continue on the same dose (1,2.5,5 OR 20 mg) and schedule of parsaclisib and 140 mg of ibrutinib as that provided in the parent Protocol at the time of the rollover.

Group III: parsaclisib Experimental Treatment 1 Intervention

Participants will continue on the same dose (1,2.5,5 OR 20 mg) and schedule of parsaclisib as that provided in the parent Protocol at the time of the rollover.

Group IV: parsaclicib + itacitinib Experimental Treatment 1 Intervention

Participants will continue on the same dose (1,2.5,5 OR 20 mg) and schedule of parsaclisib and 100 mg of itacitinib as that provided in the parent Protocol at the time of the rollover.

Ibrutinib is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Imbruvica for:

• Chronic lymphocytic leukemia
• Mantle cell lymphoma
• Waldenström's macroglobulinemia
• Marginal zone lymphoma
• Graft-versus-host disease

Approved in United States as Imbruvica for:

• Chronic lymphocytic leukemia/small lymphocytic lymphoma
• Mantle cell lymphoma
• Waldenström's macroglobulinemia
• Marginal zone lymphoma
• Graft-versus-host disease

Approved in Canada as Imbruvica for:

• Chronic lymphocytic leukemia
• Mantle cell lymphoma
• Waldenström's macroglobulinemia
• Marginal zone lymphoma

Approved in Japan as Imbruvica for:

• Chronic lymphocytic leukemia
• Mantle cell lymphoma
• Waldenström's macroglobulinemia

Who Is Running the Clinical Trial?

Incyte Corporation

Lead 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

Ibrutinib is a powerful oral medication that effectively treats relapsed/refractory mantle cell lymphoma (MCL) and chronic lymphocytic leukaemia (CLL), showing high response rates and significantly improving survival outcomes, especially in patients with poor prognostic factors like chromosome 17 deletion (del 17p).

The drug has a good safety profile, with less than 10% of patients discontinuing treatment due to side effects, making it a promising option for patients with these types of blood cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ibrutinib: a review of its use in patients with mantle cell lymphoma or chronic lymphocytic leukaemia. Kim, ES., Dhillon, S.[2022]

Ibrutinib is a first-in-class oral Bruton's tyrosine kinase inhibitor that effectively blocks B-cell signaling, leading to reduced proliferation and increased cell death in B cell malignancies, including chronic lymphocytic leukaemia (CLL) and mantle cell lymphoma (MCL).

It has received FDA approval for treating MCL in previously treated patients based on phase Ib/II study results and is currently undergoing further phase III trials for CLL, diffuse large B cell lymphoma (DLBCL), and other B cell cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ibrutinib: first global approval. Cameron, F., Sanford, M.[2022]

The combination of ibrutinib and nivolumab demonstrated an acceptable safety profile in 141 patients with relapsed or refractory B-cell malignancies, with only one dose-limiting toxicity reported, indicating that this treatment approach is generally safe for patients.

Preliminary results showed promising efficacy, with overall response rates of 61% in high-risk chronic lymphocytic leukaemia, 33% in follicular lymphoma, and 36% in diffuse large B-cell lymphoma, suggesting that this combination therapy could be effective for these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and activity of ibrutinib in combination with nivolumab in patients with relapsed non-Hodgkin lymphoma or chronic lymphocytic leukaemia: a phase 1/2a study. Younes, A., Brody, J., Carpio, C., et al.[2021]

In a study involving 122 patients with advanced solid tumors, the combination of ibrutinib and durvalumab showed an acceptable safety profile, with adverse events consistent with known effects of both drugs.

However, the antitumor activity was limited, with overall response rates of only 2% for pancreatic cancer, 3% for breast cancer, and 0% for non-small cell lung cancer, indicating that this combination may not be effective for these types of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase 1b/2 Study of the Bruton Tyrosine Kinase Inhibitor Ibrutinib and the PD-L1 Inhibitor Durvalumab in Patients with Pretreated Solid Tumors. Hong, D., Rasco, D., Veeder, M., et al.[2021]

Ibrutinib is an effective oral treatment for patients with relapsed/refractory mantle cell lymphoma (MCL) and chronic lymphocytic leukaemia (CLL), showing a 68% overall response rate in MCL and significant improvements in progression-free survival and overall survival in CLL patients, including those with specific genetic mutations.

The drug has a good safety profile, with less than 10% of patients discontinuing treatment due to adverse effects, making it a promising option for patients with various B-cell malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Ibrutinib: A new drug of B-cell malignancies]. Thieblemont, C.[2021]

Ibrutinib (Imbruvica) is an effective treatment for chronic lymphocytic leukemia, targeting specific pathways to inhibit cancer cell growth.

Tasimelteon (Hetlioz) is beneficial for individuals with non-24-hour sleep-wake disorder, helping to regulate sleep patterns, while anti-inhibitor coagulant complex (Feiba) is used to prevent or reduce bleeding episodes in patients with hemophilia A or B, demonstrating its efficacy in managing bleeding risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmaceutical approval update. Goldenberg, MM.[2021]

Ibrutinib is a targeted therapy specifically designed for treating chronic lymphocytic leukemia (CLL), which is a type of cancer that affects the blood and bone marrow.

This novel treatment works by inhibiting Bruton's tyrosine kinase (BTK), a key enzyme that helps cancer cells survive and proliferate, leading to improved patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ibrutinib (imbruvica): a novel targeted therapy for chronic lymphocytic leukemia. Parmar, S., Patel, K., Pinilla-Ibarz, J.[2021]

Ibrutinib is a highly effective and well-tolerated drug that inhibits Bruton's tyrosine kinase, leading to reduced B-cell activation and increased cancer cell death, particularly in chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL).

The drug has received FDA approval for treating relapsed CLL and MCL, and ongoing research is exploring its use in other blood cancers and in combination with other therapies, indicating its potential for broader applications in hematologic malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ibrutinib: a first in class covalent inhibitor of Bruton's tyrosine kinase. Davids, MS., Brown, JR.[2021]

In a phase 1b study involving patients with relapsed/refractory chronic lymphocytic leukemia, the combination of ibrutinib with bendamustine and rituximab (BR) showed a high overall response rate of 93.3%, with significant improvements in complete responses over time.

The study demonstrated that ibrutinib can enhance the efficacy of chemoimmunotherapy without adding prolonged hematologic toxicity, suggesting a promising treatment strategy for patients with this type of leukemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Bruton tyrosine kinase inhibitor ibrutinib with chemoimmunotherapy in patients with chronic lymphocytic leukemia. Brown, JR., Barrientos, JC., Barr, PM., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6543513/

Parsaclisib, a potent and highly selective PI3Kδ inhibitor, in ... Parsaclisib has demonstrated antitumor activity in relapsed or refractory B-cell NHL with the potential for improved long-term patient outcomes.

2. ashpublications.org ashpublications.org/bloodadvances/article/8/4/867/506667/A-phase-2-study-of-the-PI3K-inhibitor-parsaclisib

A phase 2 study of the PI3Kδ inhibitor parsaclisib in relapsed ... Parsaclisib, a highly selective, potent PI3Kδ inhibitor, demonstrated durable responses and an overall manageable safety profile in R/R MZL.

3. sciencedirect.com sciencedirect.com/science/article/pii/S0022356524257943

Parsaclisib Is a Next-Generation Phosphoinositide 3 ... Our results provide the mechanistic basis to fully support the ongoing efforts in the development of parsaclisib for treating patients with B-cell malignancies.

4. tandfonline.com tandfonline.com/doi/full/10.1080/10428194.2024.2331626

Safety and efficacy of parsaclisib in combination with ... Parsaclisib combined with SOC therapies had an expected safety profile and promising efficacy in patients with R/R B-cell lymphomas.

5. thelancet.com thelancet.com/journals/eclinm/article/PIIS2589-5370(23)00308-5/fulltext

Parsaclisib, a PI3Kδ inhibitor, in relapsed and refractory ... The median duration of parsaclisib treatment in the DG was 7.9 months (range, 1.7–27.4 months) and the median follow-up was 18.2 months (11.6– ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38407508/

Evaluation of the cardiac safety of parsaclisib, a selective ... This study evaluated the cardiac safety of parsaclisib as monotherapy based on data from 72 patients enrolled in the CITADEL-101 study.

7. ashpublications.org ashpublications.org/blood/article/140/Supplement%201/9328/487697/Safety-and-Efficacy-of-Parsaclisib-in-Combination

Safety and Efficacy of Parsaclisib in Combination with ... Parsaclisib is an investigational drug being evaluated in patients with B-cell lymphomas. ... B-Cell Lymphoma: Primary Analysis from a Phase 2...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT02018861

Study Details | NCT02018861 | A Phase 1/2, Open-Label, Dose ... Open-label, dose-escalation study in subjects with previously treated B-cell malignancies to find maximum tolerated dose (MTD) or pharmacologic active dose ...