PIT565 for B-Cell Lymphoma or Leukemia

Recruiting at 14 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

Trial Summary

What is the purpose of this trial?

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 tolerated doses (MTDs) and/or recommended doses (RDs), schedule and route of administration in relapsed and/or refractory B-cell Non-Hodgkin lymphoma (R/R B-NHL) and relapsed and/or refractory B-cell acute lymphoblastic leukemia (R/R B-ALL).

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.

What data supports the effectiveness of the drug PIT565 for B-Cell Lymphoma or Leukemia?

The research highlights the effectiveness of similar treatments like idelalisib, which targets a specific pathway in B-cell malignancies, showing high anti-tumor activity. This suggests that targeting similar pathways could be effective for B-cell lymphoma or leukemia. ^{1 2 3 4 5}

What makes the drug PIT565 unique for treating B-cell lymphoma or leukemia?

PIT565 is unique because it targets specific pathways involved in B-cell lymphoma or leukemia, potentially offering a new approach compared to traditional treatments like R-CHOP, which may not be as effective for certain subtypes such as CD5+ diffuse large B-cell lymphoma. ^{6 7 8 9 10}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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 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]

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]

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 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]

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 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]

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]

References

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

Chronic lymphocytic leukemia and hairy-cell leukemia. [2007]

2. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of idelalisib for the treatment of indolent B-cell malignancies. [2022]

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

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

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

New Pharmacotherapies in Chronic Lymphocytic Leukemia. [2020]

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

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

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

De Novo CD5+ Diffuse Large B-Cell Lymphoma: Biology, Mechanism, and Treatment Advances. [2021]

7. England pubmed.ncbi.nlm.nih.gov

CD5- small B-cell leukemias are rarely classifiable as chronic lymphocytic leukemia. [2019]

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

[Pathologic characteristics of bone marrow for CD5 positive small B cell lymphoma]. [2018]

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

Prognostic impact of CD5 expression in diffuse large B-cell lymphoma in patients treated with rituximab-EPOCH. [2017]

10. Brazil 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. [2019]