In the proposed study, escalating doses of inotuzumab ozogamicin will be added to a standard pediatric inspired re-induction regimen and administered to patients with relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL). Two re-induction regimens will be tested (one without pegaspargase and one including pegaspargase) and participants will be followed for disease status, allogeneic hematopoietic cell transplant (allo HCT), veno-occlusive disease following allo HCT, and overall survival.
Inotuzumab ozogamicin has been studied as a single agent in refractory and relapsed ALL. In the relapsed setting, inotuzumab ozogamicin has been shown to achieve complete remission (CR) in 81% of patients and minimal residual disease (MRD) negativity in 78% of patients who achieve CR. In the proposed study, escalating doses of inotuzumab ozogamicin will be added to a standard pediatric inspired re-induction regimen and administered to patients with relapsed or refractory B-cell ALL. Two re-induction regimens will be tested. The first regimen is a 3-drug regimen comprised of prednisone, vincristine, and daunorubicin. The second is a 4-drug regimen comprised of prednisone, vincristine, daunorubicin, and pegaspargase. Intrathecal methotrexate (IT-methotrexate) and intrathecal cytarabine (IT-ARA-C) will be included for central nervous system (CNS) prophylaxis with both the 3-drug and 4-drug regimens. We hypothesize that combining inotuzumab ozogamicin with these regimens is safe and will improve CR rates, successful transition to allo HCT, and overall survival in patients with relapsed or refractory B-ALL.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
36
By IV, given on days 12 and 19 Inotuzumab ozogamicin is approved as a single-agent in this population (patients with B-ALL) but adding it to these drug combinations has not been tested in humans
Taken daily days 1-28 by mouth
By IV, given on days 1, 8, 15, and 22
By IV, given on days 1, 8, 15, and 22
Intrathecal, administered on day 1 only
Intrathecal, administered on days 8 and 29
By IV, given on day 4
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, United States
University of Virginia
Charlottesville, Virginia, United States
VCU Massey Cancer Center
Richmond, Virginia, United States
University of Wisconsin
Madison, Wisconsin, United States
Characterization of Adverse Events (CTCAE version 5)
A characterization of all adverse events experienced by patients receiving these drug combinations. Also, any SAEs deemed related to study treatment, including veno-occlusive disease, will be captured at any time while the participant is on-study.
Time frame: All adverse events occurring through 30 days following last dose of inotuzumab ozogamicin.
Dose-limiting toxicities
The number of dose-limiting toxicities will be used to determine the maximum tolerated dose combination for these combinations of drugs
Time frame: From initiation of inotuzumab ozogamicin through 30 days following the last dose of inotuzumab ozogamicin
Informative course of treatment
Percent of patients that receive enough treatment to be informative to the study
Time frame: For each participant, up to the 29 days of study treatment
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.