Parsaclisib + Standard Therapy for Non-Hodgkin's Lymphoma

Recruiting at 2 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Mayo Clinic

Must not be taking: Antiretrovirals

Disqualifiers: Pregnancy, CNS lymphoma, HIV, others

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

Compensation: Varies

Number of Visits: 9

Duration: 18 weeks

50 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that patients receiving other treatments for lymphoma, except corticosteroids, are excluded. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug combination used in the clinical trial for Non-Hodgkin's Lymphoma?

Research shows that the combination of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) is a standard treatment for lymphoma, and adding rituximab to this regimen (R-CHOP) has improved outcomes for aggressive B-cell non-Hodgkin lymphoma. Additionally, using growth factors like pegfilgrastim can help reduce side effects and allow full-dose delivery of chemotherapy. ^{1 2 3 4 5}

Is the combination of Parsaclisib and standard therapy for Non-Hodgkin's Lymphoma safe?

The combination of drugs like cyclophosphamide, doxorubicin, vincristine, and prednisone, often used in treating Non-Hodgkin's Lymphoma, can have serious side effects, such as heart problems from doxorubicin, especially in older patients. However, safety measures and adjustments, like substituting epirubicin for doxorubicin, have been made to reduce these risks, and toxicity is generally manageable with careful monitoring. ^{6 7 8 9 10}

What makes the Parsaclisib combination treatment unique for non-Hodgkin's lymphoma?

The Parsaclisib combination treatment is unique because it includes Parsaclisib, a novel agent not commonly used in standard regimens like R-CHOP, and combines it with other drugs like Polatuzumab Vedotin, which targets specific proteins on cancer cells, potentially offering a new approach to treating non-Hodgkin's lymphoma. ^{6 11 12 13 14}

What is the purpose of this trial?

This trial is testing a new drug called parsaclisib, sometimes combined with polatuzumab-vedotin, along with standard cancer drugs in patients with high-risk diffuse large B-cell lymphoma. Parsaclisib blocks enzymes that help cancer grow, while polatuzumab-vedotin targets and kills cancer cells. The goal is to see if this combination works better than the standard treatment alone.

Research Team

Yucai Wang

Principal Investigator

Mayo Clinic in Rochester

Eligibility Criteria

This trial is for adults with newly diagnosed, high risk diffuse large B-cell lymphoma. Participants must have certain types of this cancer (non-GCB subtype or express specific proteins), be in specific stages, and have a good performance status. They need normal organ function tests and agree to use birth control if applicable. Excluded are pregnant individuals, those with uncontrolled illnesses, HIV on antiretroviral therapy, prior CNS lymphoma involvement, severe lung disease or heart failure.

Inclusion Criteria

Measurable disease as detected by computed tomography (CT) or PET/CT

Negative urine pregnancy test done =< 7 days prior to registration for persons of childbearing potential

My cancer shows high levels of Myc protein.

Exclusion Criteria

Nursing persons

I have not had a heart attack in the last 6 months.

I do not have any uncontrolled illnesses.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive parsaclisib with R-CHOP or with polatuzumab vedotin and R-CHP for up to 6 cycles

18 weeks

6 cycles, each 21 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Every 3 months during year 1, every 4 months during year 2

Long-term follow-up

Participants who experience disease progression are followed up every 6 months until 5 years after registration

Up to 5 years

Treatment Details

Interventions

• Cyclophosphamide
• Doxorubicin Hydrochloride
• Parsaclisib
• Pegfilgrastim
• Polatuzumab Vedotin
• Prednisone
• Rituximab
• Vincristine Sulfate

Trial Overview The trial is testing the effectiveness of parsaclisib with or without polatuzumab vedotin plus standard R-CHOP therapy against R-CHOP alone. Parsaclisib inhibits enzymes for cell growth; polatuzumab delivers chemo directly to cancer cells; R-CHOP includes rituximab and various chemotherapy drugs aimed at stopping cancer spread.

Participant Groups

Group I: Arm I (parsaclisib, R-CHOP) Experimental Treatment 7 Interventions

Patients receive parsaclisib PO QD on days 1-10 or 1-14, rituximab IV or biosimilar substitute, cyclophosphamide IV over 30 minutes, doxorubicin hydrochloride IV, and vincristine sulfate IV over 15 minutes on day 1. Patients also receive prednisone PO on days 1-5 and pegfilgrastim SC or biosimilar substitute on day 2. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.

Group II: Arm II (parsaclisib, R-CHOP, polatuzumab vedotin) Active Control 8 Interventions

Patients receive parsaclisib PO once daily QD on days 1-10 or 1-14, polatuzumab vedotin IV over 90 minutes, rituximab IV or biosimilar substitute, cyclophosphamide IV over 30 minutes, doxorubicin hydrochloride IV, and vincristine sulfate IV over 15 minutes on day 1. Patients also receive prednisone PO on days 1-5 and pegfilgrastim SC or biosimilar substitute on day 2. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.

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

Approved in United States as Cytoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in European Union as Endoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in Canada as Neosar for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in Japan as Endoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

In a study of 675 patients aged 65 and older with follicular lymphoma, those who received the R-CHOP treatment as their first line of therapy had significantly longer overall survival compared to those who received it as a second line treatment.

The benefit of receiving R-CHOP as a first line was particularly notable in patients aged 80 and older and those with lower histological grades (1 or 2), indicating that early treatment may be crucial for improving outcomes in these subgroups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Impact of Sequence of Therapy for Older Patients With Follicular Lymphoma: SEER-Medicare Analysis. Xie, C., Li, R., Huang, X., et al.[2022]

In a study of 389 young patients with good-prognosis aggressive lymphoma, the high dose of CHOEP-21 did not improve event-free or overall survival compared to the standard CHOEP-21 regimen, indicating no clinical benefit from the increased dosage.

The high CHOEP regimen was associated with significantly higher toxicity, including increased rates of severe leukocytopenia, thrombocytopenia, infections, and therapy-related deaths, suggesting that the risks may outweigh any potential benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose-escalated CHOEP for the treatment of young patients with aggressive non-Hodgkin's lymphoma: II. Results of the randomized high-CHOEP trial of the German High-Grade Non-Hodgkin's Lymphoma Study Group (DSHNHL). Pfreundschuh, M., Zwick, C., Zeynalova, S., et al.[2020]

In a study of 50 patients treated with R-CHOP-14 for aggressive B-cell lymphoma, 82% achieved a complete or improved response, indicating high efficacy of this treatment regimen.

Despite its effectiveness, R-CHOP-14 was associated with significant toxicities, including grade 3-4 neutropenia in 32% of patients and peripheral neuropathy in 45%, highlighting the need for careful monitoring of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical experience with biweekly CHOP plus rituximab chemoimmunotherapy for the treatment of aggressive B-cell non-Hodgkin lymphoma. Aguiar Bujanda, D., Aguiar Morales, J., Bohn Sarmiento, U., et al.[2021]

The CHOEA-7 chemotherapy regimen, which includes cyclophosphamide, doxorubicin, vincristine, etoposide, and ara-C, has shown excellent results in treating patients with CD 20-positive non-Hodgkin's lymphoma.

Adding rituximab to the CHOEA-7 regimen (RCHOEA-7) further enhances treatment efficacy, indicating a promising approach for improving outcomes in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Results of dose-intense, dose-impact weekly combination chemotherapy with rituximab for patients with CD 20-positive B-cell non-Hodgkin's lymphoma]. Uzuka, Y., Saitou, Y., Saitou, K., et al.[2015]

The CEOP chemotherapy regimen, which substitutes epirubicin for doxorubicin, demonstrated a high efficacy with a complete remission rate of 64.3% in 186 patients with intermediate- or high-grade non-Hodgkin lymphoma, particularly benefiting elderly patients.

Long-term follow-up showed that 79.8% of patients who achieved complete remission remained disease-free at a median of 86.9 months, indicating that CEOP is not only effective but also well-tolerated, with no deaths from cardiac toxicity reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term follow-up of patients with intermediate or high-grade non-Hodgkin lymphoma treated with a combination of cyclophosphamide, epirubicin, vincristine, and prednisone. Rossini, F., Terruzzi, E., Perego, D., et al.[2015]

In a study of 115 patients with Waldeyer's ring diffuse large B-cell lymphoma, those treated with dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin plus rituximab (DA-EPOCH-R) showed significantly better progression-free survival (PFS) and overall survival (OS) compared to those receiving standard R-CHOP treatment, with 2-year PFS rates of 90.1% versus 80.5%.

The DA-EPOCH-R treatment was associated with fewer deaths (2 out of 42 patients) compared to R-CHOP (9 out of 42 patients) during a median follow-up of 45 months, while both treatments had similar clinical responses and treatment-related toxicities, indicating that DA-EPOCH-R is a safer and more effective option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose-adjusted EPOCH-R vs. R-CHOP in frontline management of Waldeyer's ring diffuse large B-cell lymphoma: a retrospective study from a single institution. Liang, Y., Liu, X., Yang, J., et al.[2023]

In a study of 20 patients with untreated poor prognosis diffuse large B-cell lymphoma (DLBCL), the two-weekly dose-adjusted EPOCH-like chemotherapy (DA-EDOCH14-R) showed a promising three-year progression-free survival (PFS) rate of 95%, compared to 74% in a previous trial with a three-weekly regimen.

The treatment was well-tolerated with manageable toxicity and no therapy-related deaths, highlighting its safety, especially for patients with a high-risk prognosis (age-adjusted International Prognostic Index of 3), where PFS reached 100% compared to just 30% in the previous trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Two-weekly dose-adjusted (DA)-EPOCH-like chemotherapy with high-dose dexamethasone plus rituximab (DA-EDOCH14-R) in poor-prognostic untreated diffuse large B-cell lymphoma. García-Suárez, J., Flores, E., Callejas, M., et al.[2015]

The medication instruction sheet (MIS) developed for patients receiving R-CHOP therapy effectively predicted 71% of adverse drug reactions (ADRs) during the treatment period, demonstrating its usefulness in managing these reactions.

The MIS accurately matched the onset timing of infusion reactions and peripheral neuropathy, although its effectiveness was lower for predicting thrombocytopenia-related ADRs, indicating areas for improvement in monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of Medication Instruction Sheets for Patients Undergoing R-CHOP Therapy in Non-Hodgkin's Lymphoma. Uchida, M., Kawai, R., Hisamitsu, R., et al.[2022]

The current standard treatment for follicular lymphoma is a combination of chemotherapy and rituximab, specifically the R-CHOP regimen, which has been widely used and is effective.

Bendamustine combined with rituximab has shown excellent efficacy and tolerability in treating low-grade lymphomas, making it a promising alternative therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ongoing trials in low-grade lymphoma. Burchardt, A.[2021]

In a study involving 561 patients with chronic lymphocytic leukaemia, the standard treatment of fludarabine, cyclophosphamide, and rituximab showed a longer median progression-free survival of 55.2 months compared to 41.7 months for the bendamustine and rituximab combination, indicating that the standard therapy is more effective.

However, the bendamustine and rituximab combination was associated with significantly fewer severe side effects, such as neutropenia and infections, making it a potentially safer alternative for patients, especially those over 65 years.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-line chemoimmunotherapy with bendamustine and rituximab versus fludarabine, cyclophosphamide, and rituximab in patients with advanced chronic lymphocytic leukaemia (CLL10): an international, open-label, randomised, phase 3, non-inferiority trial. Eichhorst, B., Fink, AM., Bahlo, J., et al.[2022]

Rituximab, a chimeric anti-CD20 monoclonal antibody, has shown to induce responses in nearly 50% of patients with relapsed follicular/low-grade non-Hodgkin's lymphoma, with complete remissions occurring in 6% of cases, highlighting its efficacy in treating this type of cancer.

The drug is generally well tolerated, with common side effects being mild to moderate fevers and chills, and it is also effective against various other B-cell malignancies, suggesting its potential for broader applications in both cancer treatment and autoimmune disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab: clinical development and future directions. Cheson, BD.[2019]

References

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

Elderly patients with aggressive non-Hodgkin's lymphoma treated with CHOP chemotherapy plus granulocyte-macrophage colony-stimulating factor: identification of two age subgroups with differing hematologic toxicity. [2017]

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

The Impact of Sequence of Therapy for Older Patients With Follicular Lymphoma: SEER-Medicare Analysis. [2022]

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

A dose-finding study of liposomal daunorubicin with CVP (COP-X) in advanced NHL. [2020]

4. England pubmed.ncbi.nlm.nih.gov

Dose-escalated CHOEP for the treatment of young patients with aggressive non-Hodgkin's lymphoma: II. Results of the randomized high-CHOEP trial of the German High-Grade Non-Hodgkin's Lymphoma Study Group (DSHNHL). [2020]

5. Italy pubmed.ncbi.nlm.nih.gov

Clinical experience with biweekly CHOP plus rituximab chemoimmunotherapy for the treatment of aggressive B-cell non-Hodgkin lymphoma. [2021]

6. Japan pubmed.ncbi.nlm.nih.gov

[Results of dose-intense, dose-impact weekly combination chemotherapy with rituximab for patients with CD 20-positive B-cell non-Hodgkin's lymphoma]. [2015]

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

Long-term follow-up of patients with intermediate or high-grade non-Hodgkin lymphoma treated with a combination of cyclophosphamide, epirubicin, vincristine, and prednisone. [2015]

8. China pubmed.ncbi.nlm.nih.gov

Dose-adjusted EPOCH-R vs. R-CHOP in frontline management of Waldeyer's ring diffuse large B-cell lymphoma: a retrospective study from a single institution. [2023]

9. England pubmed.ncbi.nlm.nih.gov

Two-weekly dose-adjusted (DA)-EPOCH-like chemotherapy with high-dose dexamethasone plus rituximab (DA-EDOCH14-R) in poor-prognostic untreated diffuse large B-cell lymphoma. [2015]

10. Greece pubmed.ncbi.nlm.nih.gov

Evaluation of Medication Instruction Sheets for Patients Undergoing R-CHOP Therapy in Non-Hodgkin's Lymphoma. [2022]

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

Hematologic malignancies: new developments and future treatments. [2019]

12. Switzerland pubmed.ncbi.nlm.nih.gov

Ongoing trials in low-grade lymphoma. [2021]

13. England pubmed.ncbi.nlm.nih.gov

First-line chemoimmunotherapy with bendamustine and rituximab versus fludarabine, cyclophosphamide, and rituximab in patients with advanced chronic lymphocytic leukaemia (CLL10): an international, open-label, randomised, phase 3, non-inferiority trial. [2022]

14. England pubmed.ncbi.nlm.nih.gov

Rituximab: clinical development and future directions. [2019]