Inotuzumab Ozogamicin in Treating Younger Patients With Relapsed or Refractory CD22 Positive B Acute Lymphoblastic Leukemia
|ClinicalTrials.gov Identifier: NCT02981628|
Recruitment Status : Active, not recruiting
First Posted : December 5, 2016
Last Update Posted : December 26, 2017
|Condition or disease||Intervention/treatment||Phase|
|Childhood B Acute Lymphoblastic Leukemia Recurrent Childhood Acute Lymphoblastic Leukemia Refractory Childhood Acute Lymphoblastic Leukemia||Biological: Inotuzumab Ozogamicin Other: Laboratory Biomarker Analysis||Phase 2|
I. To determine the morphologic response rate (complete response [CR] + complete response with incomplete hematologic recovery [CRi]) following one cycle of treatment with inotuzumab ozogamicin (InO) in children with relapsed or refractory CD22+ B acute lymphoblastic leukemia (B-ALL).
I. To determine the CR/CRi rate following 2 cycles of InO therapy.
II. To determine the safety of single agent InO administered at the adult recommended phase 2 dose (RP2D) to pediatric patients with relapsed or refractory CD22+ B-ALL.
III. To determine the level of minimal residual disease (MRD) by flow cytometry in responding patients.
IV. To determine the incidence, severity, and outcomes of sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD) of the liver in patients during InO therapy and following subsequent treatment, including myeloablative hematopoietic stem cell transplantation (HSCT).
V. To estimate the 3-year event-free survival (EFS), 3-year overall survival (OS), and among responders duration of CR/CRi for pediatric patients with relapsed or refractory B-ALL treated with InO.
Patients receive inotuzumab ozogamicin intravenously (IV) over 60 minutes on days 1, 8, and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days, every 3 months for 1 year, and then yearly for 4 years.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||56 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 2 Study of Inotuzumab Ozogamicin (NSC# 772518) in Children and Young Adults With Relapsed or Refractory CD22+ B-Acute Lymphoblastic Leukemia (B-ALL)|
|Actual Study Start Date :||June 5, 2017|
|Estimated Primary Completion Date :||June 2019|
|Estimated Study Completion Date :||June 2019|
Experimental: Treatment (inotuzumab ozogamicin)
Patients receive inotuzumab ozogamicin IV over 60 minutes on days 1, 8, and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Biological: Inotuzumab Ozogamicin
Other: Laboratory Biomarker Analysis
- Morphologic response (CR + CRi) [ Time Frame: Up to 28 days ]The response rate will be estimated as the percent of eligible and evaluable responders (CR/CRi). A one-sided lower 95% Agresti-Coull confidence limit will be calculated.
- Duration of CR/CRi [ Time Frame: Up to 3 years ]Among responding patients, three-year complete continuous response will also be estimated using duration of CR/CRi for the overall responding group and stratified by whether or not the patients proceed to HSCT.
- EFS [ Time Frame: From study entry to first event (induction failure, induction death, relapse, second malignancy, remission death), or date of last follow-up, assessed at 3 years ]Standard errors and confidence intervals for EFS will be calculated using Peto's method.
- Incidence of adverse events of SOS/VOD of liver evaluated according to NCI CTCAE version 5.0 [ Time Frame: Up to 5 years ]The incidence, severity, and outcomes of SOS/VOD of the liver in patients during InO therapy and following subsequent treatment including myeloablative HSCT will be described. Safety monitoring (for VOD/SOS) will be performed using Pocock continuous stopping bounds.
- Incidence of dose-limiting toxicities at RP2D evaluated according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: Up to 42 days ]Toxicity tables will be constructed to summarize the observed incidence by type of toxicity and grade. For a given reporting period, a patient will be counted only once for a given toxicity for the worst grade of that toxicity reported for that patient. Safety monitoring (for DLT) will be performed using Pocock continuous stopping bounds.
- Level of MRD assessed in bone marrow by flow cytometry [ Time Frame: Up to 5 years ]MRD negativity rates (< 0.01% detectable leukemia cells) will be estimated.
- Morphologic response (CR + CRi) [ Time Frame: Up to 56 days ]The response rate will be estimated as the percent of eligible and evaluable responders (CR/CRi). A one-sided lower 95% Agresti-Coull confidence limit will be calculated.
- OS [ Time Frame: From study entry to death or date of last follow-up, assessed at 3 years ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02981628
|United States, Pennsylvania|
|Childrens Oncology Group|
|Philadelphia, Pennsylvania, United States, 19104|
|Principal Investigator:||Maureen O'Brien||Children's Oncology Group|