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

Stanford University

Status and phase: Enrolling; Phase 1

Conditions: Lymphoblastic Leukemia

Treatments: Drug: Dasatinib

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT05993949

IRB-68603

NCI-2023-05591 (Registry Identifier)

Details and patient eligibility

About

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.

Enrollment: 20 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No 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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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20 participants in 1 patient group

Dasatinib

Experimental group

Description:

Oral dasatinib 100mg

Treatment:

Drug: Dasatinib