Clinical trial NCT05993949: 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
Overall status: RECRUITING
Phase: PHASE1
Conditions: Lymphoblastic Leukemia
Keywords: Leukemia
CAR T cell therapy
Brexucabtagene Autoleucel
Dasatinib
Lead sponsor: Stanford University
Sponsor class: OTHER
Collaborators: name: Kite, A Gilead Company
First posted: 2023-08-15
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Feasibility of dasatinib pulses
timeFrame: 1 month
Secondary outcomes:
measure: Safety of oral dasatinib pulses
timeFrame: 2 years
measure: Overall response rate
timeFrame: 3 months
measure: Complete Response (CR)
timeFrame: 3 months
measure: MRD-negative Complete Response (CR)
timeFrame: 3 months
measure: Duration of CR in responders
timeFrame: 2 years
measure: Progression Free Survival (PFS) following Tecartus plus dasatinib
timeFrame: 2 years
measure: Overall Survival (OS) following Tecartus plus dasatinib
timeFrame: 2 years
Other outcomes:
Locations:
city: Palo Alto
country: United States
facility: Stanford University
state: California
Study officials:
affiliation: Stanford University
name: Lori Muffly, M.D.
role: PRINCIPAL_INVESTIGATOR
References: