Study of PIT565 in Relapsed and/or Refractory B-cell Malignancies

B-cell Acute Lymphoblastic Leukemia (B-ALL) Clinical Trial

Official title:

A Phase I, Open-label, Multi-center Study of PIT565 in Patients With Relapsed and/or Refractory B-cell Malignancies

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05397496
• Other study ID #: CPIT565A12101
• Secondary ID: 2022-000367-45
• Status: Recruiting
• Phase: Phase 1
• Start date: October 3, 2022
• Est. completion date: June 5, 2028

Study information

• Verified date: May 2024
• Source: Novartis
• Contact: Novartis Pharmaceuticals
• Phone: 1-888-669-6682
• Email: novartis.email[@]novartis.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

Description:

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 in two independent groups (group A: R/R B-NHL and B: R/R B-ALL) and a dose expansion part in three independent groups (relapsed and/or refractory large B-cell lymphoma (R/R LBCL) who received CAR-T therapy (A2) or not (A1), and R/R B-ALL (B1)).

During the dose escalation, the safety (including the dose-dose limiting toxicity (DLT) relationship) and tolerability of PIT565 will be assessed, and schedule(s), route(s) of administration and dose(s) will be identified for use in the expansion part based on the review of these data. The recommended dose (RD) will also be guided by the available information on pharmacokinetics (PK), pharmacodynamics (PD), and preliminary anti-tumor activity. The dose escalation will be guided by an adaptive Bayesian logistic regression model (BLRM) following the Escalation with Overdose Control (EWOC) principle.

Different schedules (once weekly (Q1W) or once every 2 weeks (Q2W) with and without priming dose) and routes of administrations (intravenous (i.v.) or subcutaneous (s.c.)) will be explored in the dose escalation groups.

The dose expansion will further explore the MTD(s) and/or RD(s) and the selected schedule(s) and route of administration(s) in the three patients' groups.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 140
• Est. completion date: June 5, 2028
• Est. primary completion date: June 7, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

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

• Male or female patients =18 years of age at the date of signing the informed consent form

• Eastern Cooperative Oncology Group (ECOG) performance status =2

NHL patient population

• Refractory or relapsed B-NHL

• Must have relapsed after or failed to respond to at least two prior treatment therapies including an aCD20 monoclonal antibody containing chemotherapy combination regimen

• Must have at least one bi-dimensionally measurable nodal lesion or one bi-dimensionally measurable extranodal lesion, as measured on positron emission tomography-computed tomography (PET/CT) scan

ALL patient population

• Refractory or relapsed CD19-positive B-ALL

• Morphologic disease in the bone marrow (= 5% blasts)

Exclusion Criteria:

• History of severe hypersensitivity to any ingredient of the study treatment or its excipients

• Contraindication to tocilizumab

• History of ongoing, chronic or recurrent infectious disease, or evidence of tuberculosis infection

• Malignant disease, other than that being treated in this study. Exceptions to this exclusion include the following: malignancies that were treated curatively and have not recurred within 2 years prior to study treatment; completely resected basal cell and squamous cell skin cancers, and completely resected carcinoma in situ of any type

• Active central nervous system (CNS) involvement by malignancy or presence of symptomatic CNS metastases, or CNS metastases that require local CNS-directed therapy (such as radiotherapy or surgery), or increasing doses of corticosteroids within the 2 weeks prior to the start of study treatment

• Active, known or suspected autoimmune disease other than patients with vitiligo, residual hypothyroidism only requiring hormone replacement, psoriasis not requiring systemic treatment or conditions not expected to recur

• Patients receiving systemic treatment with any immunosuppressive medication (other than steroids as described above)

Other protocol-defined inclusion/exclusion criteria may apply.

Related Conditions & MeSH terms

• B-cell Acute Lymphoblastic Leukemia (B-ALL)
• Leukemia, Lymphoid
• Lymphoma, B-Cell
• Lymphoma, Non-Hodgkin
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Biological:
• PIT565
Intravenous (i.v.) infusion or Subcutaneous (s.c.) injection

Locations

Country	Name	City	State
Belgium	Novartis Investigative Site	Gent
France	Novartis Investigative Site	Creteil
France	Novartis Investigative Site	Marseille
Israel	Novartis Investigative Site	Tel Aviv
Italy	Novartis Investigative Site	Bologna	BO
Italy	Novartis Investigative Site	Milano	MI
Japan	Novartis Investigative Site	Kashiwa	Chiba
Singapore	Novartis Investigative Site	Singapore
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	Barcelona	Catalunya
United States	University Of Miami .	Miami	Florida
United States	Memorial Sloan Kettering Cancer Ctr .	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Belgium,  France,  Israel,  Italy,  Japan,  Singapore,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence and severity of Dose Limiting Toxicities (DLTs)	Assessment of safety of study drug. A dose-limiting toxicity (DLT) is defined as an adverse event or abnormal laboratory value of CTCAE grade 3 or higher that occurs within the DLT evaluation period (28 days or 35 days depending on the schedule) and that is not primarily related to disease, disease progression, intercurrent illness, or concomitant medications with exceptions provided in the clinical protocol.	28 days or 35 days, depending on the dosing schedule
Primary	Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs)	Assessment of safety of study drug.	21 months
Primary	Frequency of dose interruptions	Assessment of tolerability of study drug	21 months
Primary	Frequency of dose reductions	Assessment of tolerability of study drug	21 months
Primary	Dose intensities	Assessment of tolerability of study drug Dose intensity is defined as the ratio of actual cumulative dose received and actual duration of exposure.	21 months
Secondary	Overall Response Rate (ORR)	Evaluation of anti-tumor activity of PIT565 for Non-Hodgkin Lymphoma will be based on the Lugano Response Criteria Classification and anti-tumor activity of PIT565 for Acute Lymphoblastic Leukemia will be based on National Comprehensive Cancer Network (NCCN) 2018 v1 guidelines. Local investigator assessment will be used for analysis of efficacy endpoints.	21 months
Secondary	Complete Response (CR) rate	Evaluation of anti-tumor activity of PIT565 for Non-Hodgkin Lymphoma will be based on the Lugano Response Criteria Classification and anti-tumor activity of PIT565 for Acute Lymphoblastic Leukemia will be based on National Comprehensive Cancer Network (NCCN) 2018 v1 guidelines. Local investigator assessment will be used for analysis of efficacy endpoints.	21 months
Secondary	Best Overall Response (BOR)	Evaluation of anti-tumor activity of PIT565 for Non-Hodgkin Lymphoma will be based on the Lugano Response Criteria Classification and anti-tumor activity of PIT565 for Acute Lymphoblastic Leukemia will be based on National Comprehensive Cancer Network (NCCN) 2018 v1 guidelines. Local investigator assessment will be used for analysis of efficacy endpoints.	21 months
Secondary	Duration Of Response (DOR)	Evaluation of anti-tumor activity of PIT565 for Non-Hodgkin Lymphoma will be based on the Lugano Response Criteria Classification and anti-tumor activity of PIT565 for Acute Lymphoblastic Leukemia will be based on National Comprehensive Cancer Network (NCCN) 2018 v1 guidelines. Local investigator assessment will be used for analysis of efficacy endpoints.	21 months
Secondary	Overall Survival (OS)	Evaluation of anti-tumor activity of PIT565 for Non-Hodgkin Lymphoma will be based on the Lugano Response Criteria Classification and anti-tumor activity of PIT565 for Acute Lymphoblastic Leukemia will be based on National Comprehensive Cancer Network (NCCN) 2018 v1 guidelines. Local investigator assessment will be used for analysis of efficacy endpoints.	33 months
Secondary	Progression Free Survival (PFS)	Evaluation of anti-tumor activity of PIT565 for Non-Hodgkin Lymphoma will be based on the Lugano Response Criteria Classification Local investigator assessment will be used for analysis of efficacy endpoints.	21 months
Secondary	Event-free survival (EFS)	Evaluation of anti-tumor activity of PIT565 for Acute Lymphoblastic Leukemia will be based on National Comprehensive Cancer Network (NCCN) 2018 v1 guidelines. Local investigator assessment will be used for analysis of efficacy endpoints.	21 months
Secondary	Maximum concentration of PIT565 (Cmax)	Pharmacokinetics (PK) parameters will be determined using non-compartmental method(s)	21 months
Secondary	Area Under the Curve of PIT565 (AUC)	Pharmacokinetics (PK) parameters will be determined using non-compartmental method(s)	21 months
Secondary	Trough concentration of PIT565 (C trough)	Pharmacokinetics (PK) parameters will be determined using non-compartmental method(s)	21 months
Secondary	Prevalence of Anti-drug antibodies (ADA) at baseline	Assessment of anti-PIT565 antibodies in serum.	Baseline
Secondary	Incidence of Anti-drug antibodies (ADA) on treatment	Assessment of anti-PIT565 antibodies in serum.	21 months