Inotuzumab Ozogamicin in Treating Younger Patients With Relapsed or Refractory CD22 Positive B Acute Lymphoblastic Leukemia
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|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 ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
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|