This phase I/II trial studies the safety, side effects and best dose of OBI-3424 and how well it works in treating patients with T-cell acute lymphoblastic leukemia or T-cell lymphoblastic lymphoma that has come back (relapsed) or does not respond to treatment (refractory). Chemotherapy drugs, such as OBI-3424, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. OBI-3424 may reduce the amount of leukemia in the body.
PRIMARY OBJECTIVES: I. To assess the safety of AKR1C3-activated prodrug OBI-3424 (OBI-3424) and to determine the maximum tolerated dose (MTD) of OBI-3424 in this regimen for patients with relapsed/refractory T-cell acute lymphoblastic leukemia (T-ALL)/T-cell lymphoblastic lymphoma (T-LBL). (Phase I) II. To assess the response rate (complete remission \[CR\] or CR with incomplete count recovery \[CRi\]) of patients treated with OBI-3424 at the maximum tolerated dose (MTD) determined in the Phase I portion of the trial in this patient population. (Phase II) SECONDARY OBJECTIVES: I. To estimate the frequency and severity of toxicities of OBI-3424 in this patient population. II. To estimate event-free survival (EFS), relapse-free survival (RFS) and overall survival (OS) in this patient population. TRANSLATIONAL MEDICINE OBJECTIVES: I. To estimate minimal/measurable residual disease (MRD) negativity (among patients who achieve CR or CRi). II. To assess AKR1C3 expression levels in this patient population. III. To evaluate associations between AKR1C3 expression and response to OBI-3424, achievement of MRD-negative remission, and relapse from remission. IV. To bank specimens for future research. OUTLINE: This is a phase I, dose-escalation study followed by a phase II study. Patients receive AKR1C3-activated prodrug OBI-3424 intravenously (IV) over 30 minutes on days 1 and 8. Treatment repeats every 21 days for up to 17 cycles in the absence of disease progression or unacceptable toxicity. Patients who have not achieved a partial remission (PR) by the 4th cycle of treatment are removed from the study (unless clinically benefiting in the opinion of the treating investigator). Patients undergo blood sample collection during screening and cerebrospinal fluid (CSF) sample collection on study. Patients also undergo bone marrow aspirate or core biopsy and may undergo computed tomography (CT) scan throughout the study. After completion of study treatment, patients are followed up every month for 1 year, every 2 months for 1 year, every 3 months for 1 year, and then every 6 months for up to 5 years from registration.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
67
Given IV
Undergo biopsy
Undergo blood and CSF sample collection
Undergo bone marrow aspirate
Undergo CT scan
University of Alabama at Birmingham Cancer Center
Birmingham, Alabama, United States
ACTIVE_NOT_RECRUITINGKingman Regional Medical Center
Kingman, Arizona, United States
RECRUITINGArkansas Children's Hospital
Little Rock, Arkansas, United States
RECRUITINGPCR Oncology
Arroyo Grande, California, United States
Maximum tolerated dose (MTD) (Phase I)
The regimen will be considered safe and the MTD determined if the dose-limiting toxicity rate is \< 33%.
Time frame: Up to 21 days
Response rate (complete remission [CR] or CR with incomplete count recovery [CRi]) (Phase II)
Time frame: Up to 5 years
Incidence of adverse events
Toxicities will be captured and described. The probability of any particular toxicity can be estimated to within at most +/- 17% (95% confidence interval).
Time frame: Up to the time of relapse, assessed up to 5 years
Overall survival
Will be estimated using the Kaplan-Meier method.
Time frame: From the day of registration on study until death from any cause with observations censored on the day of last contact for patients not known to have died, assessed up to 5 years
Event-free survival
Will be estimated using the Kaplan-Meier method.
Time frame: From the date of initial registration on study until the first of the following events: death from any cause, relapse from remission (CR or CRi) or completion of protocol therapy without documentation of CR or CRi, assessed up to 5 years
Relapse-free survival
Will be estimated using the Kaplan-Meier method.
Time frame: From the date the patient first achieves CR or CRi until relapse from CR/CRi or death from any cause, assessed up to 5 years
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City of Hope Comprehensive Cancer Center
Duarte, California, United States
RECRUITINGLoma Linda University Medical Center
Loma Linda, California, United States
RECRUITINGChildren's Hospital of Orange County
Orange, California, United States
RECRUITINGChildren's Hospital Colorado
Aurora, Colorado, United States
RECRUITINGAlfred I duPont Hospital for Children
Wilmington, Delaware, United States
RECRUITINGGolisano Children's Hospital of Southwest Florida
Fort Myers, Florida, United States
RECRUITING...and 153 more locations