This phase I/II trial studies the side effects and best dose of ADCT-602 in treating patients with B-cell lymphoblastic leukemia that has come back or does not respond to treatment. Monoclonal antibodies, such as ADCT-602, may interfere with the ability of tumor cells to grow and spread.
PRIMARY OBJECTIVES: I. Evaluate the safety and determine the maximum tolerated dose (MTD) of ADCT-602 in patients with relapsed or refractory B-cell (B)-acute lymphoblastic leukemia (ALL) in Phase 1. II. Determine the recommended dose of ADCT-602 for Phase 2. III. Evaluate the efficacy (complete response \[CR\] with incomplete marrow recovery \[CR/CRi\] rate) of ADCT-602 in Phase 2. SECONDARY OBJECTIVES: I. Evaluate the clinical activity of ADCT-602, based on duration of response (DOR), overall survival (OS), and progression-free survival (PFS). II. Characterize the pharmacokinetic (PK) profile of ADCT-602. III. Evaluate the immunogenicity of ADCT-602. IV. Characterize the effect of ADCT-602 exposure on the QT interval. EXPLORATORY OBJECTIVES: I. Obtain preliminary data on the correlation between the clinical activity and PK profile of ADCT-602 with the baseline expression of CD22 and other cluster of differentiation (CD) markers in peripheral blood. II. Assess the impact of soluble CD22 (sCD22) on ADCT-602 PK. OUTLINE: This is a dose escalation study followed by a phase II study. Patients receive ADCT-602 intravenously (IV) over 30 minutes on day 1. Courses repeat every 21 in the absence of disease progression or unacceptable toxicity. Patients who achieve CR/CRi receive ADCT-602 every 28 days. After completion of study treatment, patients are followed up at 30 days and then every 12 weeks for up to 1 year.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
37
Starting dose of ADCT-602: 30 μg/kg given by vein.
City of Hope Comprehensive Cancer
Monrovia, California, United States
M D Anderson Cancer Center
Houston, Texas, United States
Maximum tolerated dose (MTD) as determined by dose limiting toxicities (DLTs) (Phase I)
The MTD is the highest dose level in which the study has treated 6 patients with at most 1 experiencing the DLT. The 3+3 algorithm along with DLTs observed during the first 21 days of the first treatment cycle will be used to guide dose escalation/de-escalation.
Time frame: Up to 21 days
Incidence of toxicity graded according to Common Terminology Criteria for Adverse Events (CTCAE)
Toxicity is defined as DLTs.
Time frame: Up to 1 year
Recommended phase II dose of ADCT-602
The recommended dose of ADCT-602 for phase 2 is the MTD or a dose lower than MTD, which is defined based on toxicity and efficacy profile.
Time frame: Up to 21 days
Complete response (CR)/ CR with incomplete marrow recovery (CR/CRi) rate (Phase II)
Simon's two-stage design will be used. CR/CRi rate is defined as the best response (CR/CRi) noted during the study period.
Time frame: Up to 1 year
Overall response rate (ORR)
Time frame: Up to 1 year
Overall survival (OS)
Time frame: Up to 1 year
Progression-free survival (PFS)
Time frame: Up to 1 year
Measure the amount of ADCT-602 in the body at different time points.
Blood for testing the amount of ADCT-602 in the body at different time points drawn 4 times over the 6 hours after the dose.
Time frame: Up to 1 year
ADCT-602 exposure on QT interval assessed by EKG
Time frame: Baseline up to 30 days after study drug stopped
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