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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Lymphoblastic Leukemia
• Intervention / Treatment: Drug: Dasatinib

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Alyssa M Kanega; Phone Number: 650-736-1596; Email: akanegai@stanford.edu

Study Locations

• United States
  • California
    • Palo Alto, California, United States, 94305
      • Recruiting
      • Stanford University
      • Contact: Lindsay Danley; Phone Number: 650-736-0304; Email: lindsmd@stanford.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	1 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	2 years
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).	3 months
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).	3 months
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).	3 months
Duration of CR in responders		2 years
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	2 years
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	2 years

Collaborators and Investigators

• Sponsor: Stanford University
• Collaborators: Kite Pharma
• Investigators: Principal Investigator: Lori Muffly, M.D., Stanford University

Study record dates

Study Major Dates

• Study Start (Actual): October 2, 2023
• Primary Completion (Estimated): August 1, 2025
• Study Completion (Estimated): August 1, 2025

Study Registration Dates

• First Submitted: July 10, 2023
• First Submitted That Met QC Criteria: August 14, 2023
• First Posted (Actual): August 15, 2023

Study Record Updates

• Last Update Posted (Actual): February 8, 2024
• Last Update Submitted That Met QC Criteria: February 6, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Leukemia; Dasatinib; CAR T cell therapy; Brexucabtagene Autoleucel
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Dasatinib
• Other Study ID Numbers: IRB-68603

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No