Acute Lymphoblastic Leukemia
Conditions
Keywords
B-cell Acute Lymphoblastic Leukemia
Brief summary
This trial is a limited multi-center, Phase II study to evaluate inotuzumab ozogamicin (Besponsa) in pediatric patients with MRD positive CD22-positive B-lymphoblastic leukemia (B-ALL). Some patients with newly diagnosed ALL maintain low levels of MRD, despite achieving complete remission with less than 5% blasts in the bone marrow. Others experience re-emergence of low level MRD or increasing levels of MRD on therapy or post-transplant. New approaches are needed to achieve undetectable MRD in these high-risk patients. Inotuzumab ozogamicin is an antibody-drug conjugate composed of a humanized IgG subtype 4 monoclonal CD22-targeted antibody linked to calicheamicin, a potent anti-tumor antibiotic. CD22 is expressed in more than 90% of patients with B-cell ALL, making it an attractive target in this patient population. Inotuzumab ozogamicin has demonstrated exceptional activity in adults with relapsed or refractory B-ALL. Primary Objective * Assess the efficacy of inotuzumab ozogamicin in patients with MRD positive CD22+ B-ALL with 0.1 - 4.99% blasts in bone marrow. Secondary Objectives * Study the safety of inotuzumab ozogamicin when used in patients with MRD - positive CD22+ B-ALL with \< 5 % blasts in bone marrow. * Estimate the incidence, severity, and outcome of hepatotoxicity and sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD) in patients during inotuzumab ozogamicin and following subsequent treatment, including hematopoietic stem cell transplant (HSCT).
Detailed description
The drug will be administered intravenously on days 1, 8, and 15 of each 28-day cycle. Patients who do not meet the definition of treatment failure after the first cycle may receive up to five additional cycles of therapy. . After completion of study treatment, patients are followed for 1 year.
Interventions
DRUGMethylprednisolone
1 mg/kg IV x 1
DRUGInotuzumab ozogamicin
dose: 0.5 mg/m2 IV over 60 minutes, days: 1, 8 and 15 every 4 weeks (28 days per cycle) for up to 6 cycles.
DRUGMethotrexate
Intrathecal (IT) therapy
DRUGHydrocortisone
Intrathecal (IT) therapy
DRUGCytarabine
Intrathecal (IT) therapy
DRUGDiphenhydramine
1 mg/kg (max 50 mg) IV
DRUGAcetaminophen
10 mg/kg (max 650 mg) PO x 1
Sponsors
St. Jude Children's Research Hospital
Pfizer
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 21 Years
Healthy volunteers
No
Inclusion criteria
Age * Participants must be \< 22 years of age. Diagnosis * Participants must have B-ALL with persistent or rising MRD between 0.1 and 4.99% without extramedullary disease following at least two prior induction attempts, relapse or after hematopoietic stem cell transplant * Leukemia blasts demonstrating surface expression of CD22 Performance Level * Karnofsky or Lansky performance score ≥ 50% (corresponding to ECOG Score of ≥ 2). The Lansky performance score should be used for participants \< 16 years and the Karnofsky performance score for participants ≥ 16 years. Prior Therapy * Patients must have fully recovered from the acute toxic effects of all prior anticancer therapy, defined as resolution of all such toxicities to ≤ Grade 2 or lower per the inclusion/
Exclusion criteria
prior to entering this study. * At least 14 days must have elapsed since the completion of cytotoxic therapy, with the exception of standard maintenance therapy and steroids. * At least 7 days must have elapsed since completion of therapy with a biologic agent. For agents that have known adverse events occurring beyond 7 days after administration, this period prior to enrollment must be extended beyond the time during which adverse events are known to occur. * At least 3 half-lives must have elapsed since prior therapy that included a monoclonal antibody with the exception of blinatumomab. Patients must have been off blinatumomab infusion for at least 7 days and all drug related toxicity must have resolved to Grade 2 or lower as outlined in the inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Treatment response Cycle1 - count | At the end of cycle 1 (each cycle is 28 days) | Number of patients that reach MRD negative at the end of cycle 1 |
| Treatment Response Cycle 1 - percentage | At the end of cycle 1 (each cycle is 28 days) | Percentage of patients that reach MRD negative at the end of cycle 1 |
| Treatment Response Cycle 2 - count | At the end of cycle 2 (each cycle is 28 days) | Number of patients that reach MRD negative at the end of cycle 2 |
| Treatment Response Cycle 2 - percentage | At the end of cycle 2 (each cycle is 28 days) | Percentage of patients that reach MRD negative at the end of cycle 2 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Occurrence of death - count | up to 30 days from last dose of inotuzumab ozogamicin or up to 30 days post-transplant among the patients who proceed to transplant | Number of patient deaths that occur at any time during observation on study |
| Occurrence of death - percentage | up to 30 days from last dose of inotuzumab ozogamicin or up to 30 days post-transplant among the patients who proceed to transplant | Percentage of patient deaths that occur at any time during observation on study |
| Occurrence of Veno-occlusive disease (VOD) - count | up to 30 days from last dose of inotuzumab ozogamicin or up to 30 days post-transplant among the patients who proceed to transplant | Number of patients that develop VOD at any time during observation on study |
| Occurrence of Veno-occlusive disease (VOD) - percentage | up to 30 days from last dose of inotuzumab ozogamicin or up to 30 days post-transplant among the patients who proceed to transplant | Percentage of patients that develop VOD at any time during observation on study |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORSima Jeha, MD
St. Jude Children's Research Hospital
Outcome results
None listed