- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05397496
Study of PIT565 in Relapsed and/or Refractory B-cell Malignancies
A Phase I, Open-label, Multi-center Study of PIT565 in Patients With Relapsed and/or Refractory B-cell Malignancies
Study Overview
Status
Intervention / Treatment
Detailed 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.
Study Type
Enrollment (Estimated)
Phase
- Phase 1
Contacts and Locations
Study Contact
- Name: Novartis Pharmaceuticals
- Phone Number: 1-888-669-6682
- Email: novartis.email@novartis.com
Study Contact Backup
- Name: Novartis Pharmaceuticals
- Phone Number: +41613241111
- Email: novartis.email@novartis.com
Study Locations
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Gent, Belgium, 9000
- Recruiting
- Novartis Investigative Site
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Marseille, France, 13273
- Recruiting
- Novartis Investigative Site
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Tel Aviv, Israel, 6329302
- Recruiting
- Novartis Investigative Site
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BO
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Bologna, BO, Italy, 40138
- Recruiting
- Novartis Investigative Site
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MI
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Milano, MI, Italy, 20133
- Recruiting
- Novartis Investigative Site
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Chiba
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Kashiwa, Chiba, Japan, 277 8577
- Recruiting
- Novartis Investigative Site
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Singapore, Singapore, 169608
- Recruiting
- Novartis Investigative Site
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Catalunya
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Barcelona, Catalunya, Spain, 08035
- Recruiting
- Novartis Investigative Site
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Barcelona, Catalunya, Spain, 08036
- Recruiting
- Novartis Investigative Site
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New York
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New York, New York, United States, 10065
- Recruiting
- Memorial Sloan Kettering Cancer Ctr .
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Principal Investigator:
- Lia Lia Palomba
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Contact:
- Lisa Webster
- Phone Number: +1 212 639 3112
- Email: websterl@mskcc.org
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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 αCD20 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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Sequential Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: PIT565 Group A (dose escalation part)
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
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Intravenous (i.v.) infusion or Subcutaneous (s.c.) injection
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Experimental: PIT565 Group B (dose escalation part)
PIT565 in adult R/R ALL patients
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Intravenous (i.v.) infusion or Subcutaneous (s.c.) injection
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Experimental: PIT565 Group A1 (dose expansion part)
PIT565 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 who did not receive CD19-directed CAR-T therapy
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Intravenous (i.v.) infusion or Subcutaneous (s.c.) injection
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Experimental: PIT565 Group A2 (dose expansion part)
PIT565 in adult R/R LBCL (DLBCL, double/triple hit HGBCL, PMBCL, FL3B) patients who received CD19-directed CAR-T therapy
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Intravenous (i.v.) infusion or Subcutaneous (s.c.) injection
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Experimental: PIT565 Group B1 (dose expansion part)
PIT565 in adult R/R ALL patients
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Intravenous (i.v.) infusion or Subcutaneous (s.c.) injection
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Incidence and severity of Dose Limiting Toxicities (DLTs)
Time Frame: 28 days or 35 days, depending on the dosing schedule
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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.
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28 days or 35 days, depending on the dosing schedule
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Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame: 21 months
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Assessment of safety of study drug.
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21 months
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Frequency of dose interruptions
Time Frame: 21 months
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Assessment of tolerability of study drug
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21 months
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Frequency of dose reductions
Time Frame: 21 months
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Assessment of tolerability of study drug
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21 months
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Dose intensities
Time Frame: 21 months
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Assessment of tolerability of study drug Dose intensity is defined as the ratio of actual cumulative dose received and actual duration of exposure.
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21 months
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Overall Response Rate (ORR)
Time Frame: 21 months
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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.
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21 months
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Complete Response (CR) rate
Time Frame: 21 months
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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.
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21 months
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Best Overall Response (BOR)
Time Frame: 21 months
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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.
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21 months
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Duration Of Response (DOR)
Time Frame: 21 months
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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.
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21 months
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Overall Survival (OS)
Time Frame: 33 months
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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.
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33 months
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Progression Free Survival (PFS)
Time Frame: 21 months
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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.
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21 months
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Event-free survival (EFS)
Time Frame: 21 months
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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.
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21 months
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Maximum concentration of PIT565 (Cmax)
Time Frame: 21 months
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Pharmacokinetics (PK) parameters will be determined using non-compartmental method(s)
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21 months
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Area Under the Curve of PIT565 (AUC)
Time Frame: 21 months
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Pharmacokinetics (PK) parameters will be determined using non-compartmental method(s)
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21 months
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Trough concentration of PIT565 (C trough)
Time Frame: 21 months
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Pharmacokinetics (PK) parameters will be determined using non-compartmental method(s)
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21 months
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Prevalence of Anti-drug antibodies (ADA) at baseline
Time Frame: Baseline
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Assessment of anti-PIT565 antibodies in serum.
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Baseline
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Incidence of Anti-drug antibodies (ADA) on treatment
Time Frame: 21 months
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Assessment of anti-PIT565 antibodies in serum.
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21 months
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Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- CPIT565A12101
- 2022-000367-45 (EudraCT Number)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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