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

Sponsor

Stanford University (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05993949

Collaborator

Kite Pharma (Other)

Enrollment

Location

Arm

Anticipated Duration (Months)

0.8

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Lymphoblastic Leukemia	Drug: Dasatinib	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

20 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Phase 1b Study of Brexucabtagene Autoleucel Plus Dasatinib in Adults With Acute Lymphoblastic Leukemia

Anticipated Study Start Date :

Aug 1, 2023

Anticipated Primary Completion Date :

Aug 1, 2025

Anticipated Study Completion Date :

Aug 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dasatinib Oral dasatinib 100mg	Drug: Dasatinib 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

Arm

Intervention/Treatment

Experimental: Dasatinib

Oral dasatinib 100mg

Drug: Dasatinib

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

Outcome Measures

Primary Outcome Measures

Feasibility of dasatinib pulses [1 month]
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 [2 years]
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 [3 months]
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) [3 months]
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) [3 months]
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 [2 years]
Progression Free Survival (PFS) following Tecartus plus dasatinib [2 years]
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 [2 years]
OS is defined as the time from the date of initial disease diagnosis to the date of death from any cause

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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