This phase I trial studies the side effects and best dose of inotuzumab ozogamicin when given with 3 and 4 drug standard chemotherapy regimen in treating patients with B-cell acute lymphoblastic leukemia that has come back (relapsed) or does not respond to treatment (refractory). Inotuzumab ozogamicin is a monoclonal antibody, called inotuzumab, linked to a toxic agent called ozogamicin. Inotuzumab attaches to CD22 positive cancer cells in a targeted way and delivers ozogamicin to kill them. Chemotherapy drugs, such as daunorubicin, vincristine, cytarabine, methotrexate, and pegaspargase, 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. Anti-inflammatory drugs, such as prednisone lower the body’s immune response and are used with other drugs in the treatment of some types of cancer. Giving inotuzumab ozogamicin with standard chemotherapy may work better in treating patients with B-cell acute lymphoblastic leukemia compared to inotuzumab ozogamicin alone.
Additional locations may be listed on ClinicalTrials.gov for NCT03962465.
See trial information on ClinicalTrials.gov for a list of participating sites.
PRIMARY OBJECTIVES:
I. To describe the safety of combination re-induction regimens (3-drug and 4-drug) with inotuzumab ozogamicin.
II. To determine the maximum tolerated dose (MTD) of inotuzumab ozogamicin when administered in combination with 3-drug and 4-drug re-induction regimens.
EXPLORATORY OBJECTIVES:
I. To obtain preliminary data on the complete remission rate of inotuzumab ozogamicin administered in combination with a 3-drug re-induction regimen.
II. To obtain preliminary data on the complete remission rate of inotuzumab ozogamicin administered in combination with a 4-drug re-induction regimen.
III. To obtain preliminary data on overall and relapse-free survival.
IV. To obtain preliminary data on the rate of transition to allogeneic stem cell transplant.
V. To describe the incidence of veno-occlusive disease.
VI. To obtain preliminary estimates of the change (before, during and after inotuzumab ozogamicin therapy) in:
VIa. Levels of circulating pro-thrombotic tissue factor (TF) and extracellular vesicles (EVs).
VIb. Frequency of circulating B-1 cells.
VIc. Plasma levels of anti-phosphocholine (PC) and anti-malondialdehyde (MDA) immunoglobulin M (IgM) antibodies.
VII. To obtain preliminary estimates of correlations of plasma EV-TF activity, frequency of B-1 cells, and levels of IgM antibodies with clinical diagnostic criteria and incidence of veno-occlusive disease (VOD).
OUTLINE: This is a dose-escalation study of inotuzumab ozogamicin. Patients are assigned to 1 of 2 parts.
PART 1 (3-DRUG REGIMEN): Patients receive daunorubicin hydrochloride intravenously (IV) over 3-15 or 30 minutes on days 1, 8, 15, and 22, vincristine sulfate IV over 3-5 or 15 minutes on days 1, 8, 15, and 22, and prednisone orally (PO) twice daily (BID) on days 1-28, and inotuzumab ozogamicin IV over 1 hour on days 12 and 19 in the absence of disease progression or unacceptable toxicity. Patients also receive cytarabine intrathecally (IT) on day 1 and methotrexate sodium IT on days 8 and 29 for central nervous system (CNS) prophylaxis in the absence of disease progression or unacceptable toxicity.
PART 2 (4-DRUG REGIMEN): Patients receive treatment as in Part 1 and also receive pegaspargase IV over 2 hours on day 4 in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days and then every 3 months for up to 3 years.
Lead OrganizationUniversity of Virginia Cancer Center
Principal InvestigatorMichael G. Douvas
