Polatuzumab + Rituximab for Lymphoproliferative Disorders

Recruiting at 1 trial location

Overseen By Neha Mehta-shah, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Washington University School of Medicine

Must not be taking: Investigational agents

Disqualifiers: CNS involvement, Peripheral neuropathy, others

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

Compensation: Varies

Number of Visits: 1

Duration: 4-6 months

12 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for post-transplant lymphoproliferative disorder (PTLD), a type of cancer that can occur after organ or bone marrow transplants. The study combines two drugs, polatuzumab vedotin (Polivy) and rituximab, to determine if they work better together than rituximab alone. Researchers believe this combination might be safer and more effective, potentially avoiding the harsh side effects of standard chemotherapy. Individuals who have not yet been treated for CD20-positive PTLD and have had an organ or stem cell transplant may be eligible to participate. The trial will also examine how the tumor's environment and certain viruses could affect the disease's outcome. As a Phase 1/Phase 2 trial, this study focuses on understanding how the treatment works in people and measuring its effectiveness in an initial, smaller group.

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, if you are on investigational agents or have certain medical conditions, you may not be eligible to participate. It's best to discuss your specific medications with the trial team.

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

Research has shown that polatuzumab vedotin combined with rituximab is generally well-tolerated by patients with certain types of B-cell lymphomas. Studies report common side effects such as low white blood cell count, tiredness, diarrhea, and nausea. These side effects were expected and manageable.

When polatuzumab vedotin is used with rituximab and CHP (a mix of chemotherapy drugs), studies have demonstrated a predictable safety profile. While some side effects can occur, they are not surprising and can be effectively managed. Patients treated with this combination showed better treatment responses and survival rates compared to those on a standard treatment plan.

Overall, these treatments have shown promise in managing certain blood disorders, but like any medical treatment, there are risks. Participants considering joining a trial should discuss these findings and any concerns with their healthcare provider. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Polatuzumab vedotin combined with Rituximab for lymphoproliferative disorders because it offers a targeted approach different from traditional chemotherapy. Polatuzumab vedotin is an antibody-drug conjugate that specifically targets cancer cells, delivering the chemotherapy agent directly to them, which could potentially reduce side effects compared to standard treatments like R-CHOP. This combination could provide a more precise attack on cancer cells, enhancing effectiveness and possibly improving remission rates in patients who are either low-risk or high-risk based on interim response assessments.

What evidence suggests that this trial's treatments could be effective for lymphoproliferative disorders?

Research has shown that combining polatuzumab vedotin and rituximab holds promise for treating certain B-cell lymphomas. In this trial, some participants will receive only polatuzumab vedotin and rituximab, which previously demonstrated that 82.9% of patients with untreated diffuse large B-cell lymphoma (DLBCL) did not experience disease progression after six months. Other participants will receive polatuzumab vedotin and rituximab with CHP (a mix of cyclophosphamide, doxorubicin, and prednisone), which significantly prevents disease progression compared to the standard R-CHOP treatment. These findings suggest that these combinations could also be effective for patients with post-transplant lymphoproliferative disorder (PTLD), a type of lymphoma that can occur after an organ transplant. ^{5 6 7 8 9}

Who Is on the Research Team?

Neha Mehta-shah, M.D.

Principal Investigator

Washington University School of Medicine

Are You a Good Fit for This Trial?

This trial is for adults with CD20-positive post-transplant lymphoproliferative disorder (PTLD) who haven't been treated before. They should have adequate blood counts, organ function, and be able to consent. Pregnant or breastfeeding individuals are excluded, as well as those with certain infections, heart conditions, neuropathy, or other serious health issues.

Inclusion Criteria

My blood and organ functions are within normal ranges, except for issues caused by my lymphoma.

You have an absolute neutrophil count of at least 1.0 K/cumm.

You possess the mental capacity and are willing to sign a legally binding document of consent.

Exclusion Criteria

Current ejection fraction < 40% on transthoracic echocardiogram or multigated acquisition (MUGA) scan

HIV viral load < 200 copies/mm3 by standard clinical assays

I am on a stable antiretroviral regimen.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive polatuzumab vedotin and rituximab in cycles, with additional treatment based on risk assessment

4-6 months

Multiple visits per cycle, including Day 1, Day 8, and Day 15 for initial cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

What Are the Treatments Tested in This Trial?

Interventions

• CHP
• Polatuzumab Vedotin
• Rituximab

Trial Overview The study tests polatuzumab vedotin combined with rituximab in patients with PTLD. It aims to see if this combo can avoid the toxicity of traditional chemotherapy while being safe and effective. The trial will also examine tumor environment factors and anellovirus presence as potential prognostic markers.

How Is the Trial Designed?

Group I: Polatuzumab vedotin + Rituximab + CHP (Safety Lead-in High Risk/Lack of Interim Complete Remission)) Experimental Treatment 3 Interventions

* Cycle 1 (21 days) * Day 1: polatuzumab vedotin + rituximab * Day 8: rituximab * Day 15: rituximab * Cycle 2 (21 days) * Day 1: polatuzumab vedotin + rituximab * After Cycle 2, a response assessment will be performed. Patients who show anything other than a complete response (and are therefore determined to be high risk) will receive polatuzumab vedotin + rituximab + CHP (cyclophosphamide + doxorubicin + prednisone) on Day 1 of each 21-day cycle for 4 additional cycles, followed by 2 final cycles of CHP alone on Day 1 (8 cycles of treatment total).

Group II: Polatuzumab vedotin + Rituximab + CHP (Expansion High Risk/Lack of Interim Complete Remission) Experimental Treatment 3 Interventions

* Cycle 1 (21 days) * Day 1: polatuzumab vedotin + rituximab * Day 8: rituximab * Day 15: rituximab * Cycle 2 (21 days) * Day 1: polatuzumab vedotin + rituximab * After Cycle 2, a response assessment will be performed. Patients who show anything other than a complete response (and are therefore determined to be high risk) will receive polatuzumab vedotin + rituximab + CHP (cyclophosphamide + doxorubicin + prednisone) on Day 1 of each 21-day cycle for 4 additional cycles, followed by 2 final cycles of CHP alone on Day 1 (8 cycles of treatment total).

Group III: Polatuzumab vedotin + Rituximab (Safety Lead-in Low Risk/Interim Complete Remission) Experimental Treatment 2 Interventions

* Cycle 1 (21 days) * Day 1: polatuzumab vedotin + rituximab * Day 8: rituximab * Day 15: rituximab * Cycle 2 (21 days) * Day 1: polatuzumab vedotin + rituximab * After Cycle 2, a response assessment will be performed. Patients who show a complete response (and are therefore determined to be low risk) will continue to receive polatuzumab vedotin + rituximab on Day 1 of each 21-day cycle for 4 additional cycles (6 cycles of treatment total).

Group IV: Polatuzumab vedotin + Rituximab (Expansion Low Risk/Interim Complete Remission) Experimental Treatment 2 Interventions

* Cycle 1 (21 days) * Day 1: polatuzumab vedotin + rituximab * Day 8: rituximab * Day 15: rituximab * Cycle 2 (21 days) * Day 1: polatuzumab vedotin + rituximab * After Cycle 2, a response assessment will be performed. Patients who show a complete response (and are therefore determined to be low risk) will continue to receive polatuzumab vedotin + rituximab on Day 1 of each 21-day cycle for 4 additional cycles (6 cycles of treatment total).

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

Approved in United States as CHP for:

• Diffuse Large B-Cell Lymphoma (DLBCL)
• High-Grade B-Cell Lymphoma (HGBL)

Approved in European Union as CHP for:

• Diffuse Large B-Cell Lymphoma (DLBCL)
• High-Grade B-Cell Lymphoma (HGBL)

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

Published Research Related to This Trial

Rituximab, a targeted therapy for B-lineage lymphoma, can increase the risk of opportunistic infections like Pneumocystis jiroveci pneumonia (PCP), particularly during periods of neutropenia, as seen in two reported cases.

Despite the rarity of PCP in lymphoma patients treated with rituximab, timely diagnosis and management can lead to successful treatment, highlighting the need for vigilance regarding this potential complication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pneumocystis jiroveci pneumonia in patients with non-Hodgkin's lymphoma receiving chemotherapy containing rituximab. Chang, H., Yeh, HC., Su, YC., et al.[2019]

In a study of 40 patients with low-grade or follicular B-cell non-Hodgkin's lymphoma, the combination of Rituxan (Rituximab) and CHOP chemotherapy resulted in a high overall response rate of 95%, with 55% achieving complete remission.

The combination therapy showed promising safety, with common side effects being manageable, and it also indicated potential for clearing minimal residual disease, as evidenced by the conversion of the bcl-2 translocation from positive to negative in several patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of patients with low-grade B-cell lymphoma with the combination of chimeric anti-CD20 monoclonal antibody and CHOP chemotherapy. Czuczman, MS., Grillo-López, AJ., White, CA., et al.[2022]

A 56-year-old man developed dilated cardiomyopathy after receiving rituximab and bendamustine for chronic lymphocytic leukemia, highlighting a potential serious cardiovascular side effect of rituximab.

Despite the adverse reaction, the patient fully recovered after treatment with medications for cardiomyopathy and supportive care, emphasizing the importance of monitoring for such effects in patients undergoing rituximab therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reversible Cardiomyopathy after Rituximab Treatment in a Chronic Lymphocytic Leukemia Patient. Girkar, N., Zaki, S., Pawar, S., et al.[2022]

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]

In a clinical trial involving 196 patients with high-risk diffuse large cell lymphoma, the addition of rituximab to the dose-dense chemotherapy regimen CEOP-14 did not significantly improve treatment outcomes compared to CEOP-14 alone, with similar complete response rates (76% vs 74%).

Both treatment regimens showed comparable long-term outcomes, with 5-year tumor-progression-free survival (TTP) rates of 74% for CEOP-R and 72% for CEOP-14, indicating that while the dense-dose regimen is well tolerated, rituximab does not enhance efficacy in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose dense (CEOP-14) vs dose dense and rituximab (CEOP-14 +R) in high-risk diffuse large cell lymphoma. Avilés, A., Nambo, MJ., Neri, N., et al.[2019]

In a pooled analysis of 150 patients with HIV-associated aggressive B-cell non-Hodgkin lymphoma, those treated with R-EPOCH showed significantly better event-free survival (EFS) and overall survival (OS) compared to those receiving R-CHOP, particularly in patients with a CD4 count ≥100/μL.

Patients with CD4 counts <50/μL experienced a much higher rate of treatment-related deaths (37% vs 6%), indicating that lower immune function increases the risk of lethal toxicity during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pooled analysis of AIDS malignancy consortium trials evaluating rituximab plus CHOP or infusional EPOCH chemotherapy in HIV-associated non-Hodgkin lymphoma. Barta, SK., Lee, JY., Kaplan, LD., et al.[2022]

Rituximab has revolutionized lymphoma treatment, showing effectiveness as a single agent in all types of B-cell lymphomas, both indolent and aggressive.

Combining rituximab with chemotherapy (like CHOP) significantly improves treatment outcomes for large-cell lymphomas without adding significant toxicity, establishing it as the standard of care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab and chemotherapy for aggressive lymphomas: a significant advance in therapy. Hagemeister, FB.[2015]

Rituximab, when added to standard chemotherapy, significantly improved survival rates in patients with non-Hodgkin's lymphoma.

In patients with chronic B-cell lymphocytic leukemia, the addition of rituximab to fludarabine-based regimens enhanced both response rates and overall survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Review of the safety and feasibility of rapid infusion of rituximab. Atmar, J.[2022]

In a study of 100 lymphoma patients receiving either R-CHOP or CHOP treatment, severe pulmonary complications were observed more frequently in the R-CHOP group (18.3%) compared to CHOP (13.8%), although this difference was not statistically significant.

Continuous steroid use for conditions other than lymphoma significantly increased the risk of pulmonary infections, highlighting the need for careful monitoring of patients during lymphoma treatment to manage potential pulmonary complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Severe pulmonary adverse effects in lymphoma patients treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) regimen plus rituximab. Lim, KH., Yoon, HI., Kang, YA., et al.[2022]

A phase 3 study involving 407 treatment-naïve patients with diffuse large B-cell lymphoma demonstrated that HLX01, a biosimilar to rituximab, has comparable efficacy to the reference drug, with overall response rates of 94.1% for HLX01 and 92.8% for rituximab, falling within the pre-defined equivalence margin.

The safety profiles of HLX01 and rituximab were similar, with nearly identical rates of treatment-emergent adverse events (99.5% vs. 99.0%) and serious adverse events (34.0% vs. 32.5%), confirming that HLX01 is a safe alternative to rituximab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 3 study of rituximab biosimilar HLX01 in patients with diffuse large B-cell lymphoma. Shi, Y., Song, Y., Qin, Y., et al.[2021]

In a study of 250 patients with indolent non-Hodgkin lymphomas, both R-CVP and R-CHOP regimens followed by rituximab maintenance showed similar efficacy in terms of event-free survival and progression-free survival after a median follow-up of over 5 years.

R-CVP demonstrated significantly lower rates of severe adverse events compared to R-CHOP, making it a safer option for induction treatment in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-line R-CVP versus R-CHOP induction immunochemotherapy for indolent lymphoma with rituximab maintenance. A multicentre, phase III randomized study by the Polish Lymphoma Research Group PLRG4. Walewski, J., Paszkiewicz-Kozik, E., Michalski, W., et al.[2020]

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]

Citations

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Effectiveness and Safety of Polatuzumab Vedotin-Based ... The 6-month PFS rate was 82.9% in untreated DLBCL patients, which was significantly better than 52.7% in R/R DLBCL patients (p=0.046). The 1- ...

2. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK602516/

Clinical Review - Polatuzumab Vedotin (Polivy) - NCBI - NIH According to the clinical experts consulted by CADTH for this review, nearly 50% to 60% of patients with advanced stage disease can be cured with first-line ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06040320

Polatuzumab Vedotin (Pola) Plus Rituximab (R) in Patients ... The hypothesis is that this combination therapy will be safe, well-tolerated, and effective. If so, patients with PTLD will be able to be spared the toxicity of ...

4. nejm.org nejm.org/doi/full/10.1056/NEJMoa2115304

Polatuzumab Vedotin in Previously Untreated Diffuse ... Polatuzumab vedotin has shown efficacy in patients with relapsed or refractory DLBCL, both as a single agent (with an overall response of 52%) ...

5. roche.com roche.com/media/releases/med-cor-2024-12-08

Five-year results confirm Roche's Polivy combination ... Results showed a trend in reduction in the risk of death (HR 0.85; 95% CI: 0.63–1.15) for people with previously untreated DLBCL with the Polivy ...

6. polivy-hcp.com polivy-hcp.com/relapsed-refractory/br/side-effects/safety-and-tolerability.html

POLIVY® (polatuzumab vedotin-piiq) Safety Profile | R/R ... The most common adverse reactions (≥20%) in patients with relapsed or refractory DLBCL treated with POLIVY in combination with BR are neutropenia, ...

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2019/761121s000lbl.pdf

Polivy (polatuzumab vedotin-piiq) - accessdata.fda.gov Safety was also evaluated in 173 adult patients with relapsed or refractory lymphoma who received POLIVY, bendamustine, and either a rituximab product or ...

8. polivy.com polivy.com/newly-diagnosed/rchp.html

POLIVY® (polatuzumab vedotin-piiq) for certain types of ... POLIVY is a prescription medicine used with other medicines, bendamustine and a rituximab product, to treat DLBCL, NOS, in adults who have progressed after at ...

9. ema.europa.eu ema.europa.eu/en/documents/product-information/polivy-epar-product-information_en.pdf

Polivy, INN-polatuzumab vedotin - EMA Polivy in combination with bendamustine and rituximab is indicated for the treatment of adult patients with relapsed/refractory diffuse large B-cell lymphoma ( ...