Leukemia
Conditions
Brief summary
To learn if cyclophosphamide, vincristine, and dexamethasone (called mini hyper-CVD) in combination with intrathecal (delivered into the spine) chemotherapy (methotrexate, hydrocortisone, cytarabine) and compressed rituximab, blinatumomab, and inotuzumab ozogamicin (called cRIB) can help to control the disease.
Detailed description
Primary Objective: --To evaluate the clinical efficacy of the sequential combination of mini-hyper-CVD with inotuzumab ozogamicin and blinatumomab and rituximab in relapsed B-cell acute lymphoblastic leukemia (ALL) patients, based upon the complete response rate (CR). Secondary Objectives: * To summarize efficacy per response rate, overall survival (OS), event free survival (EFS), and minimal residual disease (MRD) negativity rate. * To evaluate the safety of this combination. Exploratory Objectives: --To summarize associations between genomic alterations in ALL (current biomarker expression of the disease) with relation to the incidence of transition to HSCT in patients with PR or stable disease (SD) after the induction cycle(s).
Interventions
DRUGCyclophosphamide
Given by (IV) vein
DRUGVincristine
Given by (IV) vein
DRUGBlinatumomab
Given by (IV) vein
DRUGMethotrexate
Given by (IV) vein
DRUGCytarabine
Given by (IV) vein
DRUGMercaptopurine
Given by (IV) vein
DRUGPrednisone
Given by PO
DRUGPegfilgrastim
Given by (IV) vein
DRUGInotuzumab ozogamicin
Given by (IV) vein
DRUGRituximab
Given by (IV) vein
DRUGDexamethasone
Given by (IV) vein
Sponsors
M.D. Anderson Cancer Center
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Years to 25 Years
Healthy volunteers
No
Inclusion criteria
* Pediatric, adolescent, or young adult patients with B-ALL as per NCCN v2.2021 and WHO classification in relapse or primary refractory and, either/both of the following: • Unable to receive anthracyclines (see section 3.1.8) or is PEG-asparaginase intolerant. * For leukemia: Patients must have ≥ 5% blasts expressing CD19 and CD22 in the bone marrow as assessed by morphology or flow cytometry. However, if an adequate bone marrow sample cannot be obtained, patients may be enrolled if there is unequivocal evidence of leukemia with ≥ 5% blasts in the peripheral blood. * If patient does not have CD20, they can still be enrolled but will not receive rituximab. * Performance status: Lansky ≥ 50 for patients who are ≤ 16 years old and Karnofsky ≥ 50% for patients who are \> 16 years old. * Patients with asymptomatic CNS leukemia are eligible (see also Exclusion Criterion 3.2.2.) * Age \> = 1 years of age and less than 25 years of age. * The following baseline laboratory data: * Total serum bilirubin ≤1.5x upper limit of normal (ULN). Patients with known Gilbert's syndrome may have a total bilirubin up to ≤3 x ULN. * Adequate renal function per age51 unless related to the disease. Estimated glomerular filtration rate ≥ 60 mL/min/1.73 m2 based on local institutional practice for age-appropriate determination (eg, Schwartz formula for pediatric patients or Cockcroft Gault formula for adults). * Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) ≤3 x ULN; ≤5 x ULN in case of suspected leukemic liver involvement * Females of childbearing potential must have a negative serum or urine beta human chorionic gonadotropin (β-HCG) pregnancy test result within 14 days prior to the first dose of study drugs and must agree to use one of the following effective contraception methods during the study and 30 days after the last treatment and 8 months after the last dose of inotuzumab and 12 months after the last dose of rituximab. Effective methods of birth control include: * Birth control pills, shots, implants (placed under the skin by a health care provider) or patches (placed on the skin) * Intrauterine devices (IUDs) * Condom or occlusive cap (diaphragm or cervical/vault caps) used with Spermicide * Abstinence * Males need to inform the doctor right away if the partner becomes pregnant or suspects pregnancy. While in this study and for 30 days after the last treatment the patient should not donate sperm for the purposes of reproduction. He will need to use a condom while in this study and for 30 days after the last treatment and 5 months after the last dose of inotuzumab. * Patients with cardiac disease, include but not limited to: (Left ventricular ejection fraction (EF) \< 50% (as determined by the Biplane Simpson method) (but not per
Exclusion criteria
3.2.3.1), or who have received \>450mg/m2 of doxorubicin and cannot receive anthracyclines.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0 | through study completion; an average of 1 year. |
Countries
United States
Contacts
CONTACTDavid McCall, MD
PRINCIPAL_INVESTIGATORDavid McCall, MD
M.D. Anderson Cancer Center
Outcome results
None listed