Lymphoblastic Leukemia
Conditions
Brief summary
The purpose of this study is to improve upon the TINI study treatment. The study will test the ability of a type of immunotherapy called blinatumomab to clear persistent leukemia. Blinatumomab targets CD19 which is located on the leukemia cells outer membrane.
Interventions
DRUGDexamethasone
Given orally (PO) or naso-gastrically (NG) or intravenously (IV).
DRUGMitoxantrone
Given IV
DRUGPEG asparaginase
Given IV
DRUGBortezomib
Given IV
DRUGVorinostat
Taken PO or NG
DRUGMercaptopurine
Given PO or NG.
DRUGMethotrexate
Given IV, IM or PO
DRUGBlinatumomab
Will be administered at 15 mcg/m2/day for 28 days following induction and reinduction
DRUGZiftomenib
3+3 dose escalation will be done. Dose level 1 will start at 75% of the adult recommended phase two dosing which has been established in phase I studies. Based on tolerability, we will either de-escalate to 50% RP2D (dose level -1) or escalate to 100% RP2D
Sponsors
Tanja Andrea Gruber
Pediatric Oncology Experimental Therapeutics Investigators' Consortium
Amgen
Lucile Packard Foundation for Children's Health
Kura Oncology, Inc.
United States Department of Defense
Cannonball Kid's Cancer
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 1 Years
Healthy volunteers
No
Inclusion criteria
* Patient is ≤ 365 days of age at the time of diagnosis. * Patient has newly diagnosed CD19 positive acute lymphoblastic leukemia (ALL) or acute undifferentiated leukemia. Subjects with bilineage or biphenotypic acute leukemia are eligible provided they express CD19. Patients with CD19 positive mature B-cell ALL who carry a KMT2A rearrangement are eligible. * Limited prior therapy, including hydroxyurea for 72 hours or less, systemic glucocorticoids for one week or less, cytarabine for 72 hours or less, one dose of vincristine, and one dose of intrathecal chemotherapy. * Written informed consent following Institutional Review Board, NCI, FDA, and OHRP Guidelines.
Exclusion criteria
* Patients with prior therapy, other than therapy specified in inclusion criteria. * Patients with mature B-cell ALL that do not have a KMT2A rearrangement or patients with acute myelogenous (AML) or T-cell ALL. * Patients with Down syndrome. * Inability or unwillingness of legal guardian/representative to give written informed consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Minimal Residual Disease | 5 years and 2 months | Proportion of patients who are minimal residual disease positive at the end of Induction Intensification |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Ziftomenib Minimum safe and Biologically-Effective Dose in Combination with Chemotherapy | 5 years and 6 months | To determine the estimated minimum safe and biologically-effective dose of Ziftomenib in combination with chemotherapy, on the basis of observed DLTs, MRD assessments, and pharmacokinetic studies |
| Event Free Survival | 8 years | To estimate the 3-year event-free survival for subjects treated on study |
| Overall Survival | 8 years | To estimate the 3-year overall survival for subjects treated on study |
Countries
Canada, United States
Contacts
Primary ContactTanja A Gruber, MD, PhD
Outcome results
None listed