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

Primary Purpose

B-cell Non-Hodgkin Lymphoma (B-NHL), B-cell Acute Lymphoblastic Leukemia (B-ALL)

Status
Recruiting
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
PIT565
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for B-cell Non-Hodgkin Lymphoma (B-NHL) focused on measuring Phase I, Trispecific antibody, Non-Hodgkin lymphoma, Acute Lymphoblastic Leukemia, PIT565

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Memorial Sloan Kettering Cancer CenterRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

PIT565 Group A (dose escalation part)

PIT565 Group B (dose escalation part)

PIT565 Group A1 (dose expansion part)

PIT565 Group A2 (dose expansion part)

PIT565 Group B1 (dose expansion part)

Arm Description

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

PIT565 in adult R/R ALL patients

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

PIT565 in adult R/R LBCL (DLBCL, double/triple hit HGBCL, PMBCL, FL3B) patients who received CD19-directed CAR-T therapy

PIT565 in adult R/R ALL patients

Outcomes

Primary Outcome Measures

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.
Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs)
Assessment of safety of study drug.
Frequency of dose interruptions
Assessment of tolerability of study drug
Frequency of dose reductions
Assessment of tolerability of study drug
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.

Secondary Outcome Measures

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.
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.
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.
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.
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.
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.
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.
Maximum concentration of PIT565 (Cmax)
Pharmacokinetics (PK) parameters will be determined using non-compartmental method(s)
Area Under the Curve of PIT565 (AUC)
Pharmacokinetics (PK) parameters will be determined using non-compartmental method(s)
Trough concentration of PIT565 (C trough)
Pharmacokinetics (PK) parameters will be determined using non-compartmental method(s)
Prevalence of Anti-drug antibodies (ADA) at baseline
Assessment of anti-PIT565 antibodies in serum.
Incidence of Anti-drug antibodies (ADA) on treatment
Assessment of anti-PIT565 antibodies in serum.

Full Information

First Posted
May 25, 2022
Last Updated
July 13, 2023
Sponsor
Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT05397496
Brief Title
Study of PIT565 in Relapsed and/or Refractory B-cell Malignancies
Official Title
A Phase I, Open-label, Multi-center Study of PIT565 in Patients With Relapsed and/or Refractory B-cell Malignancies
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 3, 2022 (Actual)
Primary Completion Date
February 28, 2025 (Anticipated)
Study Completion Date
February 27, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief 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).
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
B-cell Non-Hodgkin Lymphoma (B-NHL), B-cell Acute Lymphoblastic Leukemia (B-ALL)
Keywords
Phase I, Trispecific antibody, Non-Hodgkin lymphoma, Acute Lymphoblastic Leukemia, PIT565

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
140 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
PIT565 Group A (dose escalation part)
Arm Type
Experimental
Arm Description
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
Arm Title
PIT565 Group B (dose escalation part)
Arm Type
Experimental
Arm Description
PIT565 in adult R/R ALL patients
Arm Title
PIT565 Group A1 (dose expansion part)
Arm Type
Experimental
Arm Description
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
Arm Title
PIT565 Group A2 (dose expansion part)
Arm Type
Experimental
Arm Description
PIT565 in adult R/R LBCL (DLBCL, double/triple hit HGBCL, PMBCL, FL3B) patients who received CD19-directed CAR-T therapy
Arm Title
PIT565 Group B1 (dose expansion part)
Arm Type
Experimental
Arm Description
PIT565 in adult R/R ALL patients
Intervention Type
Biological
Intervention Name(s)
PIT565
Intervention Description
Intravenous (i.v.) infusion or Subcutaneous (s.c.) injection
Primary Outcome Measure Information:
Title
Incidence and severity of Dose Limiting Toxicities (DLTs)
Description
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.
Time Frame
28 days or 35 days, depending on the dosing schedule
Title
Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description
Assessment of safety of study drug.
Time Frame
21 months
Title
Frequency of dose interruptions
Description
Assessment of tolerability of study drug
Time Frame
21 months
Title
Frequency of dose reductions
Description
Assessment of tolerability of study drug
Time Frame
21 months
Title
Dose intensities
Description
Assessment of tolerability of study drug Dose intensity is defined as the ratio of actual cumulative dose received and actual duration of exposure.
Time Frame
21 months
Secondary Outcome Measure Information:
Title
Overall Response Rate (ORR)
Description
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.
Time Frame
21 months
Title
Complete Response (CR) rate
Description
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.
Time Frame
21 months
Title
Best Overall Response (BOR)
Description
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.
Time Frame
21 months
Title
Duration Of Response (DOR)
Description
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.
Time Frame
21 months
Title
Overall Survival (OS)
Description
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.
Time Frame
33 months
Title
Progression Free Survival (PFS)
Description
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.
Time Frame
21 months
Title
Event-free survival (EFS)
Description
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.
Time Frame
21 months
Title
Maximum concentration of PIT565 (Cmax)
Description
Pharmacokinetics (PK) parameters will be determined using non-compartmental method(s)
Time Frame
21 months
Title
Area Under the Curve of PIT565 (AUC)
Description
Pharmacokinetics (PK) parameters will be determined using non-compartmental method(s)
Time Frame
21 months
Title
Trough concentration of PIT565 (C trough)
Description
Pharmacokinetics (PK) parameters will be determined using non-compartmental method(s)
Time Frame
21 months
Title
Prevalence of Anti-drug antibodies (ADA) at baseline
Description
Assessment of anti-PIT565 antibodies in serum.
Time Frame
Baseline
Title
Incidence of Anti-drug antibodies (ADA) on treatment
Description
Assessment of anti-PIT565 antibodies in serum.
Time Frame
21 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Novartis Pharmaceuticals
Phone
1-888-669-6682
Email
novartis.email@novartis.com
First Name & Middle Initial & Last Name or Official Title & Degree
Novartis Pharmaceuticals
Phone
+41613241111
Email
novartis.email@novartis.com
Facility Information:
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jason Cardona
Phone
+1 212 639 3112
Email
cardonaj@mskcc.org
First Name & Middle Initial & Last Name & Degree
Lia Lia Palomba
Facility Name
Novartis Investigative Site
City
Gent
ZIP/Postal Code
9000
Country
Belgium
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Marseille
ZIP/Postal Code
13273
Country
France
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Tel Aviv
ZIP/Postal Code
6329302
Country
Israel
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Bologna
State/Province
BO
ZIP/Postal Code
40138
Country
Italy
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Milano
State/Province
MI
ZIP/Postal Code
20133
Country
Italy
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Kashiwa
State/Province
Chiba
ZIP/Postal Code
277 8577
Country
Japan
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Singapore
ZIP/Postal Code
169608
Country
Singapore
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Barcelona
State/Province
Catalunya
ZIP/Postal Code
08035
Country
Spain
Individual Site Status
Recruiting

12. IPD Sharing Statement

Plan to Share IPD
No

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

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