A041501, A Phase III Trial to Evaluate the Efficacy of the Addition of Inotuzumab Ozogamicin (a Conjugated Anti-CD22 Monoclonal Antibody) to Frontline Therapy in Young Adults (Ages 18-39 Years) with Newly Diagnosed Precursor B-Cell ALL
Categories (click each to see list of all clinical trials associated with that category): Leukemia/Myelodysplastic syndromes (MDS)/Myeloproliferative disorders (MPD)
Current Status: Open to accrual
Phase: III
Principal Investigator: Gundabolu, Krishna
Eligibility: https://clinicaltrials.gov/ct2/show/NCT03150693#eligibility
Summary
Primary objectives
(1) Confirmation of tolerability: To confirm tolerability of the combination regimen with the addition of inotuzumab ozogamicin to the pediatric-inspired regimen of CALGB 10403.
(2) Phase III: To determine whether the addition of inotuzumab ozogamicin significantly improves the event-free survival (EFS) in patients who achieve an induction response achieved with the pediatric-inspired regimen of CALGB 10403, without censoring for transplant.
Secondary objectives
(1) To determine the impact of inotuzumab ozogamicin on disease-free (DFS) and overall survival (OS) in patients who achieve an induction response.
(2) To determine whether the addition of inotuzumab ozogamicin significantly improves the event-free survival (EFS) in patients who achieve an induction response achieved with the pediatric-inspired regimen of CALGB 10403, with censoring for transplant.
(3) To determine the impact of inotuzumab ozogamicin on minimal residual disease (MRD) and correlate this with the EFS, DFS and OS.
(4) To determine the prognosis based on patients LDA gene signature in terms of EFS, DFS, and OS after treatment with or without inotuzumab ozogamicin when added to the C10403 backbone regimen.
(5) To evaluate the toxicity and tolerability of the addition of inotuzumab ozogamicin to the pediatric-inspired regimen of CALGB 10403.
Correlative science objectives
(1) Minimal Residual Disease (MRD)
To assess both the correlation of MRD post-induction and at sequential timepoints with LDA signature.
To evaluate the influence of MRD status (detectable vs. not and as a continuous measure) in relation to EFS both in the univariate setting as well as adjusting for other clinical features including initial WBC, ethnicity, gender and age at diagnosis.
To evaluate the impact of inotuzumab on the kinetics of MRD during treatment with inotuzumab in patients randomized to the experimental treatment arm.
(2) Molecular Genetics of AYA ALL (Alliance A041501-LC1)
To perform genomic analyses to identify and evaluate the incidence and clinical significance of recurring novel fusion genes including those associated with the BCR-ABL1-like signature and to correlate with MRD status, CR rate, EFS and OS.
(3) Pharmacogenomics (Alliance A041501-PP1)
To assess whether rs4958351 is correlated with L-asp allergic reaction in the AYA population. Secondary endpoints will be any L-asp adverse event, CR rate, MRD, EFS, and OS.
To assess the incidence of inherited genetic variants in the GR1A1, CEP72, CPA2, TPMT, NUDT15, GRIN3A, GRIK1, and other genes (which can be found using a GWAS), are correlated with increased rates of target toxicities including peripheral neuropathy, hepatotoxicity, pancreatitis, myelosuppression, neurotoxicity, thrombosis, and osteonecrosis, and correlate with treatment discontinuation and other clinical response parameters including CR rate, EFS, and OS.
(4) Asparaginase Pharmacokinetics in AYA (Alliance A041501-PP2)
To evaluate asparaginase pharmacokinetics in adolescents and young adults, and investigate its correlation with toxicities and treatment outcomes.
To investigate the effect of anti-PEG and anti-ASP antibodies (PEG-ASP) on ASP enzyme activity.
(5) Health Outcomes: Adherence to Oral Chemotherapy and Outcomes in AYAs with ALL (Alliance A041501-HO1)
To measure adherence to oral 6MP and Methotrexate in AYAs with ALL and to examine sociodemographic and behavioral determinants of adherence.
To determine the impact of adherence on risk of relapse among AYAs with ALL.