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Study of Brexucabtagene Autoleucel Plus Dasatinib in Adults With Acute Lymphoblastic Leukemia

Primary Purpose

Lymphoblastic Leukemia

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Dasatinib
Sponsored by
Stanford University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Lymphoblastic Leukemia focused on measuring Leukemia, CAR T cell therapy, Brexucabtagene Autoleucel, Dasatinib

Eligibility Criteria

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

Inclusion Criteria: Relapsed or refractory B-precursor ALL defined as one of the following: Primary refractory disease (>=5% blasts or persistent extramedullary disease following induction therapy) First or later relapse of marrow or extramedullary disease Persistence of MRD defined as detectable ALL by flow cytometry, PCR, or next-generation sequencing Relapsed or refractory disease after allogeneic transplant provided individual is at least 100 days from transplant at time of enrollment Patients with isolated, asymptomatic CNS relapse will be eligible Age >=18 years Eastern cooperative oncology group (ECOG) performance status of 0-2 Adequate renal, hepatic, pulmonary and cardiac function defined as: Creatinine clearance (as estimated by Cockcroft Gault) ≥ 60 cc/min Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) ≤ 2.5 x upper limit of normal (ULN) Total bilirubin ≤ 1.5 mg/dl, except in individuals with Gilbert's syndrome. Cardiac ejection fraction ≥ 50%, no evidence of clinically significant pericardial effusion, and no clinically significant arrhythmias Baseline oxygen saturation > 92% on room air QTc ≤ 500ms In individuals previously treated with blinatumomab, CD19 tumor expression in bone marrow or peripheral blood by flow cytometry or extramedullary site by IHC or flow cytometry Negative serum or urine beta-HCG test in females of childbearing potential within 3 weeks of enrollment Subjects of childbearing or child fathering potential must be willing to practice birth control from the time of enrollment on this study Page 10 of 83 Version 1.0 dated 27-April-2023 and for six (6) months after receiving the preparative conditioning regimen. Must be able to give informed consent. Legal authorized representative (LAR) is permitted if subject is cognitively able to provide verbal assent. Exclusion Criteria: History of dasatinib intolerance Known sensitivity or allergy to aminoglycosides or any agents/reagents used in this study Blast count > 75% in the bone marrow. History of malignancy other than non-melanoma skin cancer or carcinoma in situ (e.g. cervix, bladder, breast) unless disease free for at least 2 years Presence of CNS-3 disease with neurological changes History or presence of any CNS disorder such as a seizure disorder, cerebrovascular ischemia/hemorrhage with clinical signs or symptoms History of concomitant genetic syndrome such as Fanconi anemia, Kostmann syndrome, Shwachman-Diamond or any known bone marrow failure syndrome History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant cardiac disease within 12 months of enrollment Primary immunodeficiency Known infection with HIV, hepatitis B (HBsAg positive) or untreated hepatitis C virus Presence of fungal, bacterial, viral, or other infection that is uncontrolled or requiring IV antimicrobials for management. Salvage chemotherapy including TKIs for Ph+ ALL within 1 week prior to enrollment Pregnant or breast feeding Patients with known autoimmune disease requiring the use of systemic immunosuppressive therapy within the last year Corticosteroid therapy within 7 days prior to enrollment Acute or chronic GVHD requiring systemic treatment within 4 weeks prior to enrollment Live vaccine ≤ 4 weeks prior to enrollment Any medical condition that in the judgement of the investigator is likely to interfere with assessment of safety or efficacy of study treatment

Sites / Locations

  • Stanford UniversityRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Dasatinib

Arm Description

Oral dasatinib 100mg

Outcomes

Primary Outcome Measures

Feasibility of dasatinib pulses
Feasibility of administering oral dasatinib pulses (3 consecutive doses per week) during the first month following Tecartus infusion. Feasibility will be defined as the ability of 8 out of 20 subjects to miss no more than one cycle (defined as one week of at least three consecutive days of dasatinib) within the first month following Tecartus infusion.

Secondary Outcome Measures

Safety of oral dasatinib pulses
Defined by a description of adverse events and serious adverse events at least possibly related to dasatinib following CAR T cell therapy; it will include an analysis of the sequential toxicity boundaries in that the analysis does not lead to a pause in the study; further defined as no reports of suspected death on study.
Overall response rate
The definitions for response are primarily based on the standardized response criteria defined by National Comprehensive Cancer Network (NCCN) Guidelines (NCCN, 2021 v.2).
Complete Response (CR)
The definitions for response are primarily based on the standardized response criteria defined by National Comprehensive Cancer Network (NCCN) Guidelines (NCCN, 2021 v.2).
MRD-negative Complete Response (CR)
The definitions for response are primarily based on the standardized response criteria defined by National Comprehensive Cancer Network (NCCN) Guidelines (NCCN, 2021 v.2).
Duration of CR in responders
Progression Free Survival (PFS) following Tecartus plus dasatinib
PFS is defined as the time from the start of the investigational therapy to the date of radiographic progression
Overall Survival (OS) following Tecartus plus dasatinib
OS is defined as the time from the date of initial disease diagnosis to the date of death from any cause

Full Information

First Posted
July 10, 2023
Last Updated
October 6, 2023
Sponsor
Stanford University
Collaborators
Kite Pharma
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1. Study Identification

Unique Protocol Identification Number
NCT05993949
Brief Title
Study of Brexucabtagene Autoleucel Plus Dasatinib in Adults With Acute Lymphoblastic Leukemia
Official Title
Phase 1b Study of Brexucabtagene Autoleucel Plus Dasatinib in Adults With Acute Lymphoblastic Leukemia
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 2, 2023 (Actual)
Primary Completion Date
August 2025 (Anticipated)
Study Completion Date
August 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Stanford University
Collaborators
Kite Pharma

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
To assess the feasibility of oral dasatinib pulses (3 consecutive days per week) during the first month following infusion of brexucabtagene autoleucel (Tecartus) in adults with relapsed or refractory B-cell acute lymphoblastic leukemia.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lymphoblastic Leukemia
Keywords
Leukemia, CAR T cell therapy, Brexucabtagene Autoleucel, Dasatinib

7. Study Design

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

8. Arms, Groups, and Interventions

Arm Title
Dasatinib
Arm Type
Experimental
Arm Description
Oral dasatinib 100mg
Intervention Type
Drug
Intervention Name(s)
Dasatinib
Intervention Description
3 pulses of oral dasatinib (100 mg daily) beginning on Day 4 (+up to 2 days) for 3 days (with 4 days off), repeated weekly. The weekly 3-day pulse schedule of dasatinib may continue for up to 3 months in subjects who continue to meet the dasatinib eligibility criteria and who do not meet off treatment/off study criteria
Primary Outcome Measure Information:
Title
Feasibility of dasatinib pulses
Description
Feasibility of administering oral dasatinib pulses (3 consecutive doses per week) during the first month following Tecartus infusion. Feasibility will be defined as the ability of 8 out of 20 subjects to miss no more than one cycle (defined as one week of at least three consecutive days of dasatinib) within the first month following Tecartus infusion.
Time Frame
1 month
Secondary Outcome Measure Information:
Title
Safety of oral dasatinib pulses
Description
Defined by a description of adverse events and serious adverse events at least possibly related to dasatinib following CAR T cell therapy; it will include an analysis of the sequential toxicity boundaries in that the analysis does not lead to a pause in the study; further defined as no reports of suspected death on study.
Time Frame
2 years
Title
Overall response rate
Description
The definitions for response are primarily based on the standardized response criteria defined by National Comprehensive Cancer Network (NCCN) Guidelines (NCCN, 2021 v.2).
Time Frame
3 months
Title
Complete Response (CR)
Description
The definitions for response are primarily based on the standardized response criteria defined by National Comprehensive Cancer Network (NCCN) Guidelines (NCCN, 2021 v.2).
Time Frame
3 months
Title
MRD-negative Complete Response (CR)
Description
The definitions for response are primarily based on the standardized response criteria defined by National Comprehensive Cancer Network (NCCN) Guidelines (NCCN, 2021 v.2).
Time Frame
3 months
Title
Duration of CR in responders
Time Frame
2 years
Title
Progression Free Survival (PFS) following Tecartus plus dasatinib
Description
PFS is defined as the time from the start of the investigational therapy to the date of radiographic progression
Time Frame
2 years
Title
Overall Survival (OS) following Tecartus plus dasatinib
Description
OS is defined as the time from the date of initial disease diagnosis to the date of death from any cause
Time Frame
2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Relapsed or refractory B-precursor ALL defined as one of the following: Primary refractory disease (>=5% blasts or persistent extramedullary disease following induction therapy) First or later relapse of marrow or extramedullary disease Persistence of MRD defined as detectable ALL by flow cytometry, PCR, or next-generation sequencing Relapsed or refractory disease after allogeneic transplant provided individual is at least 100 days from transplant at time of enrollment Patients with isolated, asymptomatic CNS relapse will be eligible Age >=18 years Eastern cooperative oncology group (ECOG) performance status of 0-2 Adequate renal, hepatic, pulmonary and cardiac function defined as: Creatinine clearance (as estimated by Cockcroft Gault) ≥ 60 cc/min Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) ≤ 2.5 x upper limit of normal (ULN) Total bilirubin ≤ 1.5 mg/dl, except in individuals with Gilbert's syndrome. Cardiac ejection fraction ≥ 50%, no evidence of clinically significant pericardial effusion, and no clinically significant arrhythmias Baseline oxygen saturation > 92% on room air QTc ≤ 500ms In individuals previously treated with blinatumomab, CD19 tumor expression in bone marrow or peripheral blood by flow cytometry or extramedullary site by IHC or flow cytometry Negative serum or urine beta-HCG test in females of childbearing potential within 3 weeks of enrollment Subjects of childbearing or child fathering potential must be willing to practice birth control from the time of enrollment on this study Page 10 of 83 Version 1.0 dated 27-April-2023 and for six (6) months after receiving the preparative conditioning regimen. Must be able to give informed consent. Legal authorized representative (LAR) is permitted if subject is cognitively able to provide verbal assent. Exclusion Criteria: History of dasatinib intolerance Known sensitivity or allergy to aminoglycosides or any agents/reagents used in this study Blast count > 75% in the bone marrow. History of malignancy other than non-melanoma skin cancer or carcinoma in situ (e.g. cervix, bladder, breast) unless disease free for at least 2 years Presence of CNS-3 disease with neurological changes History or presence of any CNS disorder such as a seizure disorder, cerebrovascular ischemia/hemorrhage with clinical signs or symptoms History of concomitant genetic syndrome such as Fanconi anemia, Kostmann syndrome, Shwachman-Diamond or any known bone marrow failure syndrome History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant cardiac disease within 12 months of enrollment Primary immunodeficiency Known infection with HIV, hepatitis B (HBsAg positive) or untreated hepatitis C virus Presence of fungal, bacterial, viral, or other infection that is uncontrolled or requiring IV antimicrobials for management. Salvage chemotherapy including TKIs for Ph+ ALL within 1 week prior to enrollment Pregnant or breast feeding Patients with known autoimmune disease requiring the use of systemic immunosuppressive therapy within the last year Corticosteroid therapy within 7 days prior to enrollment Acute or chronic GVHD requiring systemic treatment within 4 weeks prior to enrollment Live vaccine ≤ 4 weeks prior to enrollment Any medical condition that in the judgement of the investigator is likely to interfere with assessment of safety or efficacy of study treatment
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Lindsay Danley
Phone
(650) 736-0304
Email
lindsmd@stanford.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lori Muffly, M.D.
Organizational Affiliation
Stanford University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Stanford University
City
Palo Alto
State/Province
California
ZIP/Postal Code
94305
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lindsay Danley
Phone
650-736-0304
Email
lindsmd@stanford.edu

12. IPD Sharing Statement

Learn more about this trial

Study of Brexucabtagene Autoleucel Plus Dasatinib in Adults With Acute Lymphoblastic Leukemia

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