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TINI 2: Total Therapy for Infants With Acute Lymphoblastic Leukemia II

Registration Number
NCT05848687
Lead Sponsor
Tanja Andrea Gruber
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
90
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
TreatmentZiftomenibParticipants who meet eligibility criteria will receive remission induction, induction intensification, consolidation I, reinduction block I, reinduction block II, consolidation II, and Maintenance. Interventions: Dexamethasone, Mitoxantrone, PEG-asparaginase, Bortezomib, Vorinostat, Mercaptopurine, Methotrexate and Vincristine, Blinatumomab, Ziftomenib
TreatmentPEG asparaginaseParticipants who meet eligibility criteria will receive remission induction, induction intensification, consolidation I, reinduction block I, reinduction block II, consolidation II, and Maintenance. Interventions: Dexamethasone, Mitoxantrone, PEG-asparaginase, Bortezomib, Vorinostat, Mercaptopurine, Methotrexate and Vincristine, Blinatumomab, Ziftomenib
TreatmentBortezomibParticipants who meet eligibility criteria will receive remission induction, induction intensification, consolidation I, reinduction block I, reinduction block II, consolidation II, and Maintenance. Interventions: Dexamethasone, Mitoxantrone, PEG-asparaginase, Bortezomib, Vorinostat, Mercaptopurine, Methotrexate and Vincristine, Blinatumomab, Ziftomenib
TreatmentMethotrexateParticipants who meet eligibility criteria will receive remission induction, induction intensification, consolidation I, reinduction block I, reinduction block II, consolidation II, and Maintenance. Interventions: Dexamethasone, Mitoxantrone, PEG-asparaginase, Bortezomib, Vorinostat, Mercaptopurine, Methotrexate and Vincristine, Blinatumomab, Ziftomenib
TreatmentBlinatumomabParticipants who meet eligibility criteria will receive remission induction, induction intensification, consolidation I, reinduction block I, reinduction block II, consolidation II, and Maintenance. Interventions: Dexamethasone, Mitoxantrone, PEG-asparaginase, Bortezomib, Vorinostat, Mercaptopurine, Methotrexate and Vincristine, Blinatumomab, Ziftomenib
TreatmentDexamethasoneParticipants who meet eligibility criteria will receive remission induction, induction intensification, consolidation I, reinduction block I, reinduction block II, consolidation II, and Maintenance. Interventions: Dexamethasone, Mitoxantrone, PEG-asparaginase, Bortezomib, Vorinostat, Mercaptopurine, Methotrexate and Vincristine, Blinatumomab, Ziftomenib
TreatmentMitoxantroneParticipants who meet eligibility criteria will receive remission induction, induction intensification, consolidation I, reinduction block I, reinduction block II, consolidation II, and Maintenance. Interventions: Dexamethasone, Mitoxantrone, PEG-asparaginase, Bortezomib, Vorinostat, Mercaptopurine, Methotrexate and Vincristine, Blinatumomab, Ziftomenib
TreatmentVorinostatParticipants who meet eligibility criteria will receive remission induction, induction intensification, consolidation I, reinduction block I, reinduction block II, consolidation II, and Maintenance. Interventions: Dexamethasone, Mitoxantrone, PEG-asparaginase, Bortezomib, Vorinostat, Mercaptopurine, Methotrexate and Vincristine, Blinatumomab, Ziftomenib
TreatmentMercaptopurineParticipants who meet eligibility criteria will receive remission induction, induction intensification, consolidation I, reinduction block I, reinduction block II, consolidation II, and Maintenance. Interventions: Dexamethasone, Mitoxantrone, PEG-asparaginase, Bortezomib, Vorinostat, Mercaptopurine, Methotrexate and Vincristine, Blinatumomab, Ziftomenib
Primary Outcome Measures
NameTimeMethod
Minimal Residual Disease5 years and 2 months

Proportion of patients who are minimal residual disease positive at the end of Induction Intensification

Secondary Outcome Measures
NameTimeMethod
Ziftomenib Minimum safe and Biologically-Effective Dose in Combination with Chemotherapy5 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 Survival8 years

To estimate the 3-year event-free survival for subjects treated on study

Overall Survival8 years

To estimate the 3-year overall survival for subjects treated on study

Trial Locations

Locations (25)

Phoenix Children's Hospital

🇺🇸

Phoenix, Arizona, United States

Arkansas Children's Hospital

🇺🇸

Little Rock, Arkansas, United States

Children's Hospital Los Angeles

🇺🇸

Los Angeles, California, United States

Valley Children's Hospital

🇺🇸

Madera, California, United States

Children's Hospital of Orange County

🇺🇸

Orange, California, United States

Stanford University

🇺🇸

Palo Alto, California, United States

Rady Children's Hospital San Diego

🇺🇸

San Diego, California, United States

Arnold Palmer Hospital for Children

🇺🇸

Orlando, Florida, United States

Children's Hospital of Minnesota

🇺🇸

Minneapolis, Minnesota, United States

Memorial Sloan Kettering Cancer Center

🇺🇸

New York, New York, United States

Novant Health - Hemby Children's Hospital

🇺🇸

Charlotte, North Carolina, United States

Doernbecher Children's Hospital

🇺🇸

Portland, Oregon, United States

Penn State Milton S Hershey Medical Center

🇺🇸

Hershey, Pennsylvania, United States

MD Anderson

🇺🇸

Houston, Texas, United States

University of Texas Health Science Center San Antonio

🇺🇸

San Antonio, Texas, United States

University of Utah Huntsman Cancer Institute

🇺🇸

Salt Lake City, Utah, United States

Children's Hospital of The King's Daughters

🇺🇸

Norfolk, Virginia, United States

University of Wisconsin Carbone Cancer Center

🇺🇸

Madison, Wisconsin, United States

Alberta Children's Hospital

🇨🇦

Calgary, Alberta, Canada

Stollery Children's Hospital

🇨🇦

Edmonton, Alberta, Canada

BC Children's Hospital

🇨🇦

Vancouver, British Columbia, Canada

McMaster Children's Hospital

🇨🇦

Hamilton, Ontario, Canada

CHU Sainte-Justine

🇨🇦

Montréal, Quebec, Canada

Montreal Children's Hospital

🇨🇦

Montréal, Quebec, Canada

Chu De Quebec

🇨🇦

Quebec City, Quebec, Canada

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