Stem Cell Transplant + Polatuzumab for Lymphoma

Overseen By Lauren Harrison, RN

Age: Any Age

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: New York Medical College

Must not be taking: Investigational agents

Disqualifiers: Prior stem cell transplant, CNS lymphoma, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 14

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of Polatuzumab Vedotin, an antibody-drug conjugate, for individuals with certain B-cell non-Hodgkin lymphomas, such as diffuse large B-cell lymphoma or follicular lymphoma. Participants will undergo a stem cell transplant and, if they respond well, will receive regular doses of Polatuzumab Vedotin to assess its impact on recovery and disease progression. Ideal candidates have previously tried other treatments without success and have achieved at least a stable response after reinduction therapy. As a Phase 1, Phase 2 trial, this research aims to understand how the treatment works in people and measure 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, you must not have received myelosuppressive chemotherapy within 2 weeks (or 4 weeks for certain drugs) before starting the study, and at least 7 days must have passed since completing therapy with a biologic agent.

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

Research has shown that polatuzumab vedotin has been studied for safety. Some studies found serious side effects in 64% of patients, with fatal reactions in 7% of cases within 90 days after the last treatment. Another study showed that about 80% of patients experienced treatment-related side effects.

While this might sound concerning, it's important to know that these studies involved people with very serious health conditions. The treatment is being tested for those who have not responded to other therapies. Side effects can sometimes be expected, but doctors weigh these against the potential benefits.

For those considering joining a trial, remember that these studies are designed to closely monitor safety. Discuss any concerns with the trial team, who can provide guidance based on specific health needs. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Polatuzumab Vedotin is unique because it specifically targets and destroys cancer cells in lymphoma by linking an antibody to a potent chemotherapy drug. Unlike traditional chemotherapy that affects both healthy and cancerous cells, Polatuzumab Vedotin delivers treatment directly to cancer cells, minimizing damage to healthy cells and potentially reducing side effects. Researchers are excited about this treatment because it represents a more precise approach to attacking lymphoma, offering hope for improved outcomes and fewer adverse effects compared to current therapies.

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

Studies have shown that Polatuzumab Vedotin, which participants in this trial may receive, effectively treats certain types of lymphoma. In patients with hard-to-treat lymphoma, the treatment led to a complete response in 52.5% of cases, meaning more than half of these patients showed no signs of cancer after treatment. Additionally, Polatuzumab Vedotin-based therapy has proven effective and safe for people with various types of diffuse large B-cell lymphoma (DLBCL), including those newly diagnosed or experiencing a recurrence. In some cases, it has helped patients live longer without disease progression. Overall, these findings suggest Polatuzumab Vedotin could be a promising option for treating lymphoma. ^{1 3 4 6 7}

Who Is on the Research Team?

Aliza Gardenswartz, MD

Principal Investigator

New York Medical College

Are You a Good Fit for This Trial?

This trial is for patients with various types of B-cell and Hodgkin Lymphoma who have had a relapse or are not responding well to initial treatments. They must be over 16, have a life expectancy greater than 6 weeks, and show adequate organ function. Patients can't join if they're pregnant, breastfeeding, have severe neuropathy, active CNS lymphoma, uncontrolled infections or are using other investigational drugs.

Inclusion Criteria

I have had a stem cell collection from my blood.

Creatinine clearance or radioisotope GFR > 60 mL/min/1.73 m2 or

My kidney function, based on my age and gender, is within the required range.

Exclusion Criteria

I have never had a stem cell transplant.

I do not have any infections that aren't responding to treatment.

I do not have severe nerve damage.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Conditioning and Autologous Stem Cell Transplantation

Patients receive one of two conditioning regimens (BEAM or CBV) before undergoing autologous stem cell transplantation (ASCT)

3-4 weeks

Polatuzumab Vedotin Therapy

Patients receive an IV dose of Polatuzumab Vedotin once every 21 days until they receive 8 doses

24 weeks

8 visits (in-person)

Follow-up

Patients are monitored every 4 months for about 2 years to assess safety and effectiveness

2 years

6 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Polatuzumab Vedotin

Trial Overview The study tests Polatuzumab Vedotin in patients post-autologous stem cell transplant (ASCT). Participants will first undergo one of two chemotherapy regimens before ASCT. If they respond well to ASCT, they'll receive Polatuzumab Vedotin every three weeks for up to eight doses.

How Is the Trial Designed?

Group I: Polatuzumab vedotin Experimental Treatment 1 Intervention

Evaluable patients for safety Patients receiving 1 dose of Polatuzumab Vedotin will be evaluable for safety. Evaluable patients for response Only in patients who are in PR or SD prior to PV and received a minimum of 3 doses will be evaluable. Evaluable patients for EFS, PFS, OS All patients who have completed conditioning and autoSCT will be evaluable for EFS, PFS, and OS.

Who Is Running the Clinical Trial?

New York Medical College

Lead Sponsor

Trials

73

Recruited

8,700+

Published Research Related to This Trial

Polatuzumab vedotin is an approved treatment for relapsed or refractory diffuse large B-cell lymphoma, specifically targeting the CD79b protein on B cells.

The drug works by delivering a cytotoxic molecule that inhibits tubulin polymerization, effectively killing the targeted cancer cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Polatuzumab Vedotin Approved for DLBCL. [2020]

In a study of 69 patients with aggressive B-cell lymphoma treated with polatuzumab vedotin combined with bendamustine and rituximab, a 50% response rate was observed, with a 24% complete response rate, indicating some efficacy in a real-world setting.

However, the median progression-free survival (PFS) was only 2.0 months, and survival was 5.3 months, which is lower than what was reported in clinical trials, particularly for patients with prior refractory disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Polatuzumab Vedotin for Relapsed/Refractory Aggressive B-cell Lymphoma: A Multicenter Post-marketing Analysis. Smith, SD., Lopedote, P., Samara, Y., et al.[2022]

Polatuzumab vedotin (pola) was well tolerated in a phase 1 study with Japanese patients suffering from relapsed/refractory B-cell non-Hodgkin lymphoma, showing no dose-limiting toxicities and an acceptable safety profile.

The study indicated promising antitumor activity, with four out of seven patients achieving objective responses, including three complete responses, suggesting that pola could be an effective treatment option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and pharmacokinetics of polatuzumab vedotin in Japanese patients with relapsed/refractory B-cell non-Hodgkin lymphoma: a phase 1 dose-escalation study. Kinoshita, T., Hatake, K., Yamamoto, K., et al.[2021]

In a study involving 85 patients with untreated diffuse large B-cell lymphoma, the combination of polatuzumab vedotin with standard chemotherapy (R-CHP or G-CHP) showed promising preliminary efficacy, with 89% of patients achieving an overall response and 77% achieving a complete response.

The safety profile of polatuzumab vedotin was manageable, with common adverse events including neutropenia and peripheral neuropathy, leading to the establishment of a recommended phase 2 dose of 1.8 mg/kg for further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Polatuzumab vedotin in combination with immunochemotherapy in patients with previously untreated diffuse large B-cell lymphoma: an open-label, non-randomised, phase 1b-2 study. Tilly, H., Morschhauser, F., Bartlett, NL., et al.[2023]

Polatuzumab vedotin (POLIVY®) is an effective treatment for adult patients with diffuse large B-cell lymphoma, approved after showing significant anti-cancer activity by delivering a potent drug directly to B cells.

The incidence of anti-drug antibodies (ADA) against polatuzumab vedotin is low, likely due to its mechanism of action that targets and kills B cells, which minimizes immune response and supports a favorable benefit/risk profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Integrated summary of immunogenicity of polatuzumab vedotin in patients with relapsed or refractory B-cell non-Hodgkin's lymphoma. Dere, RC., Beardsley, RL., Lu, D., et al.[2023]

Polatuzumab vedotin is an antibody-drug conjugate that targets CD79b on B cells, delivering a cytotoxic agent (MMAE) to inhibit cell division and induce cell death, making it a promising treatment for certain blood cancers.

In June 2019, polatuzumab vedotin received accelerated FDA approval for use with bendamustine and rituximab in adults with relapsed/refractory diffuse large B-cell lymphoma (DLBCL), and it is currently under review in the EU and in various stages of development for other related conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Polatuzumab Vedotin: First Global Approval. Deeks, ED.[2023]

Polatuzumab vedotin combined with rituximab and bendamustine (Pola-BR) was effective in achieving complete metabolic remission in two patients with aggressive B-cell lymphomas who relapsed after CAR T-cell therapy, demonstrating its potential as a bridging therapy before alloHSCT.

Both patients successfully underwent alloHSCT and remained disease-free for 362 and 195 days post-transplant, suggesting that Pola-BR may improve outcomes for patients with relapsed aggressive B-cell lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Salvage Therapy With Polatuzumab Vedotin, Bendamustine, and Rituximab Prior to Allogeneic Hematopoietic Transplantation in Patients With Aggressive Lymphomas Relapsing After Therapy With Chimeric Antigen Receptor T-Cells-Report on Two Cases. Gerhardt, K., Jentzsch, M., Georgi, T., et al.[2021]

Polatuzumab vedotin, an antibody-drug conjugate targeting CD79b, has demonstrated significant clinical effectiveness in treating follicular and diffuse large B-cell lymphoma (DLBCL), and is FDA-approved for use with bendamustine and rituximab in patients with relapsed or refractory DLBCL.

The review highlights the ongoing research and potential future applications of polatuzumab in the treatment of B-cell non-Hodgkin lymphoma, indicating its importance in expanding treatment options for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Profile of Polatuzumab Vedotin in the Treatment of Patients with Relapsed/Refractory Non-Hodgkin Lymphoma: A Brief Report on the Emerging Clinical Data. Sawalha, Y., Maddocks, K.[2022]

The POLARIX trial indicates that polatuzumab vedotin combined with chemotherapy is more effective in treating untreated large B-cell lymphoma, particularly in patients with the activated B-cell subtype.

This finding is supported by both preclinical and clinical evidence, highlighting the importance of the cell-of-origin in determining the efficacy of polatuzumab treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cell-of-Origin Effect of Polatuzumab Vedotin in Diffuse Large B-Cell Lymphoma: No Ordinary Subgroup Analysis. Russler-Germain, DA., Cliff, ERS., Bartlett, NL.[2023]

Polatuzumab vedotin (PV) is an innovative antibody-drug conjugate that has been approved by the US FDA for treating refractory/relapsed diffuse large B-cell lymphoma, particularly in patients who are not eligible for stem cell transplants.

In a pivotal Phase II trial, PV demonstrated significant efficacy and an acceptable safety profile when used in combination with bendamustine and rituximab, highlighting its potential as a valuable treatment option for this challenging condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Polatuzumab vedotin, an anti-CD79b antibody-drug conjugate for the treatment of relapsed/refractory diffuse large B-cell lymphoma. Camus, V., Tilly, H.[2021]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/41115257/

Efficacy and Safety of Glofitamab Plus Polatuzumab ... The median progression-free survival and overall survival (OS) were 12.3 and 33.8 months, respectively (median OS follow-up time, 32.7 months).

2. 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 ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO-25-00992

Efficacy and Safety of Glofitamab Plus Polatuzumab ... The primary results demonstrated high and durable responses, particularly for patients with primary refractory disease (CR rate, 52.5%) and ...

4. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/7782/528262/Effectiveness-and-Safety-of-Polatuzumab-Vedotin

Effectiveness and Safety of Polatuzumab Vedotin-Based ... Pola-based therapy was effective and safe in Chinese untreated or R/R DLBCL patients with diverse clinical characteristics.

5. polivy.com polivy.com/newly-diagnosed/rchp/results/clinical-trial-results.html

Clinical Trial Results Clinical Trial Results · POLIVY® plus R-CHP is clinically proven to be more effective than traditional chemoimmunotherapy (R-CHOP) · 27 percent.

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

POLIVY® (polatuzumab vedotin-piiq) Safety Profile | R/R ... Fatal adverse reactions occurred in 7% in the POLIVY+BR arm within 90 days of last treatment · Serious adverse reactions occurred in 64%, most often from ...

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

Polatuzumab Vedotin in Previously Untreated Diffuse ... Overall survival at 2 years did not differ significantly between the groups (88.7% [95% CI, 85.7 to 91.6] in the pola-R-CHP group and 88.6% [95% ...