PIT565 for B-Cell Lymphoma or Leukemia

Recruiting at 21 trial locations

Overseen By Novartis Pharmaceuticals

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Novartis Pharmaceuticals

Must not be taking: Immunosuppressive medications

Disqualifiers: Infectious disease, CNS involvement, others

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

Compensation: Varies

Number of Visits: Unknown

140 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called PIT565 to determine its safety and effectiveness for people with certain types of blood cancer. It targets adults with B-cell lymphoma or B-cell leukemia who have tried at least two other treatments without success. The study includes different groups to identify the best dose and method of administration. Ideal candidates are those whose cancer has returned or worsened after previous treatments and who have a measurable tumor or cancer cells in the bone marrow. This trial offers a new option for those whose other treatments have failed. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, giving participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does exclude patients receiving systemic treatment with any immunosuppressive medication. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that PIT565 is likely to be safe for humans?

Research shows that PIT565 is being tested for safety and tolerability in people with certain types of B-cell lymphoma and leukemia. This new treatment is currently in clinical trials. Earlier studies suggest that treatments like PIT565, which enhance T-cells' ability to attack cancer, have shown promise in early trials. These treatments have generally been well-tolerated, with manageable side effects.

Since PIT565 is in the early testing stages, the main goal is to determine the right dose that patients can handle without excessive side effects. Doctors are still learning about any potential side effects. Although specific data on PIT565's safety is limited, its progression to this testing stage indicates a reasonable level of safety in initial studies. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about PIT565 for treating B-cell lymphomas and leukemias because it targets cancer cells differently compared to traditional chemotherapy or immunotherapy. Unlike standard treatments like R-CHOP or CAR-T cell therapy, PIT565 focuses on a novel mechanism that enhances the body's immune response against these cancer cells. This approach could potentially lead to more effective outcomes, especially for patients who haven't responded well to existing therapies. By offering a new angle of attack, PIT565 brings hope for improved survival rates and quality of life for individuals with these challenging conditions.

What evidence suggests that PIT565 might be an effective treatment for B-cell lymphoma or leukemia?

Research shows that PIT565, administered to participants in this trial, is a promising treatment because it targets three important proteins: CD3, CD19, and CD20. These proteins appear on the surface of cancer cells in certain blood cancers, such as B-cell lymphoma and leukemia. Previous studies have shown that treatments targeting these proteins can effectively destroy cancer cells. Early signs suggest that PIT565 might work similarly by helping the immune system attack the cancer. Although limited data from human trials exist, this approach using a trispecific antibody has shown potential in other similar treatments. ^{1 2 3 5 6}

Are You a Good Fit for This Trial?

Adults over 18 with B-cell Non-Hodgkin lymphoma or acute lymphoblastic leukemia that's come back or didn't respond to treatment, including a CD20 monoclonal antibody regimen. They must have measurable disease and be in relatively good health (ECOG ≤2). Not for those with severe allergies to study ingredients, ongoing infections, other cancers within the last 2 years (with some exceptions), CNS involvement by cancer, active autoimmune diseases, or on immunosuppressants.

Inclusion Criteria

I can take care of myself but might not be able to do heavy physical work.

My leukemia has returned or is not responding to treatment, and tests show more than 5% cancer cells in my bone marrow.

Signed informed consent must be obtained prior to participation in the study

Exclusion Criteria

I have no other cancers, except for treated ones with no recurrence in 2 years, or completely removed skin cancers or in situ carcinomas.

I am not on any immune-suppressing drugs except for steroids.

My cancer has spread to my brain and needs treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Safety and tolerability of PIT565 are assessed to identify maximal tolerated doses and recommended doses in relapsed and/or refractory B-cell malignancies.

21 months

Dose Expansion

Further exploration of maximal tolerated doses and recommended doses, including selected schedules and routes of administration in specific patient groups.

21 months

Follow-up

Participants are monitored for safety and effectiveness after treatment.

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• PIT565

Trial Overview The trial is testing PIT565's safety and finding the highest dose patients can take without serious side effects in relapsed/refractory B-cell malignancies. It's an early-phase study where everyone gets PIT565 to determine how well it works and what doses are safe.

How Is the Trial Designed?

Group I: PIT565 Group B1 (dose expansion part) Experimental Treatment 1 Intervention

PIT565 in adult R/R ALL patients

Group II: PIT565 Group B (dose escalation part) Experimental Treatment 1 Intervention

PIT565 in adult R/R ALL patients

Group III: PIT565 Group A2 (dose expansion part) Experimental Treatment 1 Intervention

PIT565 RD2 in adult R/R LBCL (DLBCL, double/triple hit HGBCL, PMBCL, FL3B) patients

Group IV: PIT565 Group A1 (dose expansion part) Experimental Treatment 1 Intervention

PIT565 Recommended dose 1 (RD1) in adult R/R large B-cell lymphoma (LBCL) (DLBCL, double/triple hit High-grade B-cell lymphoma (HGBCL), Primary mediastinal large B-cell lymphoma (PMBCL), Follicular lymphoma grade 3B (FL3B)) patients

Group V: PIT565 Group A (dose escalation part) Experimental Treatment 1 Intervention

PIT565 in adult NHL patients for whom two or more lines of chemotherapy have failed and either having progressed (or relapsed) after autologous hematopoietic stem cell transplantation (HSCT), or being ineligible for or not consenting to the procedure

Who Is Running the Clinical Trial?

Novartis Pharmaceuticals

Lead Sponsor

Trials

2,963

Recruited

4,275,000+

Founded

1996

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Gleevec, Cosentyx, Entresto, Kisqali

Dr. Vas Narasimhan

Novartis Pharmaceuticals

Chief Executive Officer since 2018

MD from Harvard Medical School

Dr. Shreeram Aradhye

Novartis Pharmaceuticals

Chief Medical Officer since 2021

MD

Published Research Related to This Trial

The study reviews the clinical outcomes of newly approved drugs for chronic lymphocytic leukemia (CLL), indicating their effectiveness in treating this condition.

It also discusses promising investigational therapies that may offer new treatment options for patients with CLL in the future.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Pharmacotherapies in Chronic Lymphocytic Leukemia. Olin, JL., Canupp, K., Smith, MB.[2020]

CD5+ diffuse large B-cell lymphoma (DLBCL) is associated with poorer outcomes compared to non-CD5+ DLBCL, often affecting older female patients with advanced disease and a high risk of central nervous system relapse.

Traditional treatments like R-CHOP are less effective for CD5+ DLBCL, but higher-dose therapies such as R-DA-EPOCH and novel drugs like lenalidomide show promise in improving patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

De Novo CD5+ Diffuse Large B-Cell Lymphoma: Biology, Mechanism, and Treatment Advances. Xu, Y., Sun, W., Li, F.[2021]

In a study of 130 patients with diffuse large B-cell lymphoma (DLBCL) treated with R-EPOCH therapy, CD5-positive (CD5+) DLBCL was found in 12.3% of cases and was associated with a significantly worse overall survival (OS) of 28.13 months compared to CD5-negative (CD5-) patients, who had not reached median OS.

Patients with CD5+ DLBCL also experienced a higher rate of central nervous system relapses (33.3% vs 15.6%) and had a higher Ki67 proliferative index, indicating that CD5 expression remains a critical independent prognostic factor even when treated with R-EPOCH.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prognostic impact of CD5 expression in diffuse large B-cell lymphoma in patients treated with rituximab-EPOCH. Thakral, B., Medeiros, LJ., Desai, P., et al.[2017]

Fludarabine is currently the most effective treatment for chronic lymphocytic leukemia, helping to activate apoptosis in abnormal lymphocytes, but it does not cure the disease.

For hairy-cell leukemia, treatments like pentostatin and 2-chlorodeoxyadenosine lead to durable complete remissions in 65% to 85% of patients, showing promising efficacy with similar toxicity levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chronic lymphocytic leukemia and hairy-cell leukemia. Cheson, BD.[2007]

Idelalisib, a PI3K delta inhibitor, has shown significant anti-tumor activity in patients with chronic lymphocytic leukemia (CLL) and indolent B-cell non-Hodgkin lymphomas, marking it as the first approved treatment in this category for refractory cases.

Despite its effectiveness, idelalisib has notable side effects that limit its widespread use, highlighting the need for the development of new PI3K inhibitors that maintain high efficacy while improving safety profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of idelalisib for the treatment of indolent B-cell malignancies. Smolewski, P., Rydygier, D.[2022]

Zanubrutinib, a BTK inhibitor approved for chronic lymphocytic leukemia (CLL), shows a strong safety and efficacy profile, making it a promising treatment option for patients, especially those with relapsed mantle cell lymphoma.

The choice of BTK inhibitor in clinical practice is influenced by its effectiveness, toxicity, and potential drug interactions, with ongoing studies aimed at comparing zanubrutinib to other BTK inhibitors and exploring combination therapies for better treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An evaluation of zanubrutinib, a BTK inhibitor, for the treatment of chronic lymphocytic leukemia. Geethakumari, PR., Awan, F.[2021]

The study analyzed the bone marrow characteristics of 92 patients with CD5 positive small B cell lymphoma (SBL), revealing that the majority had chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and mantle cell lymphoma (MCL), indicating a diverse range of lymphoma types within this category.

Immunophenotypic analysis using flow cytometry was crucial for diagnosing and differentiating between types of CD5 positive SBL, particularly highlighting significant differences in marker expression between CLL and MCL patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Pathologic characteristics of bone marrow for CD5 positive small B cell lymphoma]. Peng, S., Zhu, F., You, S., et al.[2018]

In the phase III ALPINE trial, zanubrutinib, a second-generation BTK inhibitor, demonstrated superior efficacy compared to ibrutinib in patients with relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma.

Zanubrutinib not only showed a better safety profile but also significantly improved progression-free survival for patients, making it a promising treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

BTK Inhibitor Options Expand for CLL/SLL. [2023]

In a study of 42 patients with chronic B cell malignancies, CD5 expression was found to be a key marker for distinguishing B cell chronic lymphocytic leukemia (B-CLL) and mantle cell lymphoma (MCL) from hairy cell leukemia (HCL) and B cell prolymphocytic leukemia (B-PLL).

All patients with B-CLL and MCL showed CD5 expression, while HCL cases were negative for CD5, indicating that testing for CD5 can be a useful diagnostic tool in differentiating these types of leukemias.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Detection of CD5 in B-cell chronic lymphoproliferative diseases by flow cytometry: a strong expression in B-cell chronic lymphocytic leukemia. Cavalcanti Júnior, GB., Sales, VS., Cavalcanti e Silva, DG., et al.[2019]

In a study of 192 cases of B-cell lymphoproliferative disorders, only 3 cases were identified as CD5- B-cell chronic lymphocytic leukemia (B-CLL), indicating that CD5- cases are rare in this context.

The majority of CD5- cases were found to be other types of leukemias or lymphomas, suggesting that CD5- lymphoproliferative disorders are more accurately classified as non-Hodgkin lymphoma rather than B-CLL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD5- small B-cell leukemias are rarely classifiable as chronic lymphocytic leukemia. Huang, JC., Finn, WG., Goolsby, CL., et al.[2019]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05397496?term=trispecific%20antibody&cond=cancer&viewType=Table&rank=9

Study of PIT565 in Relapsed and/or Refractory B-cell ... This is an open-label, multicenter, phase I study, which primary objective is to characterize the safety and tolerability of PIT565 and to identify maximal ...

2. novartis.com novartis.com/clinicaltrials/study/nct05397496

Study of PIT565 in Relapsed and/or Refractory B-cell ... This is an open-label, multicenter, phase I study, which primary objective is to characterize the safety and tolerability of PIT565 and to identify maximal ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S000649712309701X

A Phase 1 Study of PIT565, a First-in-Class, Anti-CD3 ... This is an open-label, phase 1, multicenter study of PIT565 in patients with R/R B-NHL and R/R CD19-positive B-ALL who have relapsed/failed to respond to ≥2 ...

4. clinicaltrial.be clinicaltrial.be/en/details/27360?per_page=20&only_recruiting=0&only_eligible=0&only_active=0

Study of PIT565 in Relapsed and/or Refractory B-cell Mali... This is an open-label, multicenter, phase I study of PIT565 in patients with R/R B-NHL and R/R B-ALL. The study comprises a dose escalation part of PIT565 ...

5. researchgate.net researchgate.net/publication/376154347_A_Phase_1_Study_of_PIT565_a_First-in-Class_Anti-CD3_Anti-CD19_Anti-CD2_Trispecific_Antibody_in_Patients_with_Relapsed_andor_Refractory_B-Cell_Malignancies?_share=1

A Phase 1 Study of PIT565, a First-in-Class, Anti-CD3 ... A Phase 1 Study of PIT565, a First-in-Class, Anti-CD3, Anti-CD19, Anti-CD2 Trispecific Antibody in Patients with Relapsed and/or Refractory B-Cell Malignancies.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10351267/

T-cell redirecting therapies for B-cell non-Hodgkin lymphoma In contrast, off-the-shelf T-cell redirecting therapies have demonstrated impressive efficacy and safety profiles in early clinical trials over ...