B-cell Acute Lymphoblastic Leukemia
Conditions
Brief summary
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.
Detailed description
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.
Interventions
DRUGInotuzumab ozogamicin
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
DRUGPrednisone Pill
Taken daily days 1-28 by mouth
DRUGDaunorubicin
By IV, given on days 1, 8, 15, and 22
DRUGVincristine
By IV, given on days 1, 8, 15, and 22
DRUGCytarabine
Intrathecal, administered on day 1 only
DRUGMethotrexate
Intrathecal, administered on days 8 and 29
DRUGPegaspargase
By IV, given on day 4
Sponsors
Pfizer
Vanderbilt University
University of Wisconsin, Madison
Virginia Commonwealth University
University of Virginia
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
This is an early-phase study evaluating the safety of inotuzumab ozogamicin administered in combination with a 3-drug and 4-drug re-induction regimen in participants with relapsed or refractory B-ALL. The trial is planned to first determine the maximum tolerated dose (MTD) of the 3-drug re-induction regimen in Part 1 and then to determine the MTD of the 4-drug re-induction regimen (including pegaspargase) in Part 2.
Eligibility
Sex/Gender
ALL
Age
16 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
1. Provision of signed and dated informed consent form 2. Stated willingness to comply with all study procedures and availability for the duration of the study 3. Diagnosed with CD-22 positive\* B-cell Acute Lymphoblastic Leukemia or B-cell Lymphoblastic Lymphoma (Philadelphia chromosome negative) \* For the purposes of this study, CD-22 positive will be defined based on the analysis completed for diagnostic purposes. 4. Male or female, aged 16-60 years 5. ECOG performance status of 0-2 6. Left ventricular ejection fraction ≥ 50% measured by echocardiogram or MUGA 7. Either relapsed following remission after initial induction therapy or refractory to induction therapy 8. Adequate organ function, including serum creatinine ≤ 1.6 mg/dL OR creatinine clearance \>50 ml/min by Cockgroft-Gault formula, bilirubin ≤ 1.5 mg/dL (except in patients with Gilbert's disease), AST, ALT and alkaline phosphatase ≤ 3 x upper limit of normal (elevation exceeding this threshold of either AST OR ALT would not meet eligibility) 9. For females of reproductive potential: negative pregnancy test 10. For females and males of reproductive potential: agreement to use adequate contraception during study participation and for an additional 1 year after the end of study treatment 11. Agreement to adhere to Lifestyle Considerations throughout study duration and for 1 year following last study treatment.
Exclusion criteria
1. Past receipt of a total of ≥ 300 mg/m\^2 doxorubicin equivalents (600 mg/m\^2 daunorubicin, 60 mg/m\^2 idarubicin, 75 mg/m\^2 mitoxantrone) 2. Current or past history of pancreatitis 3. QT interval on electrocardiogram (ECG) \> 0.45 by Framingham formula 4. Known congestive heart failure 5. Known allergy to asparaginase (only an
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Characterization of Adverse Events (CTCAE version 5) | All adverse events occurring through 30 days following last dose of inotuzumab ozogamicin. | 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. |
| Dose-limiting toxicities | From initiation of inotuzumab ozogamicin through 30 days following the last dose of inotuzumab ozogamicin | The number of dose-limiting toxicities will be used to determine the maximum tolerated dose combination for these combinations of drugs |
| Informative course of treatment | For each participant, up to the 29 days of study treatment | Percent of patients that receive enough treatment to be informative to the study |
Countries
United States
Outcome results
None listed