Study to Test AKR1C3-Activated Prodrug OBI-3424 (OBI-3424) in Patients with Relapsed/Refractory T-Cell Acute Lymphoblastic Leukemia (T-ALL) or T-Cell Lymphoblastic Lymphoma (T-LBL)

Active:	Yes
Cancer Type:	Hematopoietic Malignancies Leukemia Lymphoma Non-Hodgkin Lymphoma Unknown Primary	NCT ID:	NCT04315324
Trial Phases:	Phase I Phase II	Protocol IDs:	S1905 (primary) S1905 NCI-2020-00768
Eligibility:	18 Years and older, Male and Female	Study Type:	Treatment
Study Sponsor:	SWOG
NCI Full Details:	http://clinicaltrials.gov/show/NCT04315324

Summary

This phase I/II trial studies the 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.

Objectives

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 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-3423, 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 every 4-6 weeks throughout the study. Patients also undergo bone marrow aspirate or core biopsy during screening, after two cycles of treatment and before each treatment cycle until CR/CRi and at time of disease relapse. Patients may undergo computed tomography (CT) during screening and follow up.

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.

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