ACTIVE_NOT_RECRUITING

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

Conditions

Lymphoblastic Leukemia Leukemia CAR T cell therapy Brexucabtagene Autoleucel Dasatinib

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

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

Quick Facts

Study Start:2023-10-02

Study Completion:2027-06

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:ACTIVE_NOT_RECRUITING

Study ID

NCT05993949

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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.	* 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

Inclusion Criteria

Exclusion 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.

* 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

Contacts and Locations

Principal Investigator

Lori Muffly, M.D.

PRINCIPAL_INVESTIGATOR

Stanford University

Study Locations (Sites)

Stanford University

Palo Alto, California, 94305

United States

Collaborators and Investigators

Sponsor: Stanford University

Lori Muffly, M.D., PRINCIPAL_INVESTIGATOR, Stanford University

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2023-10-02

Study Completion Date2027-06

Study Record Updates

Study Start Date2023-10-02

Study Completion Date2027-06

Terms related to this study

Keywords Provided by Researchers

Leukemia
CAR T cell therapy
Brexucabtagene Autoleucel
Dasatinib

Additional Relevant MeSH Terms

Lymphoblastic Leukemia