Back to resultsTINI 2: Total Therapy for Infants With Acute Lymphoblastic Leukemia II
Primary Purpose
Lymphoblastic Leukemia
Status
Not yet recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Dexamethasone
Mitoxantrone
PEG asparaginase
Bortezomib
Vorinostat
Mercaptopurine
Methotrexate
Blinatumomab
Ziftomenib
Sponsored by
About this trial
This is an interventional treatment trial for Lymphoblastic Leukemia
Eligibility Criteria
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 with ≥25% blasts in the bone marrow (M3), with or without extramedullary disease. Patients with CD19 positive biphenotypic acute leukemia are eligible. Patients with CD19 positive mature B-cell ALL that carry a KMT2Ar 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 does not have a KMT2Ar 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
Sites / Locations
- Stanford University
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Treatment
Arm Description
Participants 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
Outcomes
Primary Outcome Measures
Minimal Residual Disease
proportion of patients who are minimal residual disease positive at the end of induction intensification
Secondary Outcome Measures
Ziftomenib Maximum Tolerated Dose in Combination with Chemotherapy
determine the estimated maximum tolerated dose of Ziftomenib in combination with chemotherapy, on the basis of observed DLTs
Event Free Survival
Overall Survival
Full Information
NCT ID
NCT05848687
First Posted
April 27, 2023
Last Updated
September 11, 2023
Sponsor
Stanford University
Collaborators
Pediatric Oncology Experimental Therapeutics Investigators' Consortium, Amgen, Lucile Packard Foundation for Children's Health
1. Study Identification
Unique Protocol Identification Number
NCT05848687
Brief Title
TINI 2: Total Therapy for Infants With Acute Lymphoblastic Leukemia II
Official Title
TINI 2: Total Therapy for Infants With Acute Lymphoblastic Leukemia II
Study Type
Interventional
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
November 1, 2023 (Anticipated)
Primary Completion Date
December 2028 (Anticipated)
Study Completion Date
December 2033 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Stanford University
Collaborators
Pediatric Oncology Experimental Therapeutics Investigators' Consortium, Amgen, Lucile Packard Foundation for Children's Health
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lymphoblastic Leukemia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
90 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Treatment
Arm Type
Experimental
Arm Description
Participants 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
Intervention Type
Drug
Intervention Name(s)
Dexamethasone
Intervention Description
Given orally (PO) or naso-gastrically (NG) or intravenously (IV).
Intervention Type
Drug
Intervention Name(s)
Mitoxantrone
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
PEG asparaginase
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Bortezomib
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Vorinostat
Intervention Description
Taken PO or NG
Intervention Type
Drug
Intervention Name(s)
Mercaptopurine
Intervention Description
Given PO or NG.
Intervention Type
Drug
Intervention Name(s)
Methotrexate
Intervention Description
Given IV, IM or PO
Intervention Type
Drug
Intervention Name(s)
Blinatumomab
Intervention Description
Will be administered at 15 mcg/m2/day for 28 days following induction and reinduction
Intervention Type
Drug
Intervention Name(s)
Ziftomenib
Intervention Description
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
Primary Outcome Measure Information:
Title
Minimal Residual Disease
Description
proportion of patients who are minimal residual disease positive at the end of induction intensification
Time Frame
5 years and 2 months
Secondary Outcome Measure Information:
Title
Ziftomenib Maximum Tolerated Dose in Combination with Chemotherapy
Description
determine the estimated maximum tolerated dose of Ziftomenib in combination with chemotherapy, on the basis of observed DLTs
Time Frame
5 years and 6 months
Title
Event Free Survival
Time Frame
8 years
Title
Overall Survival
Time Frame
8 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
1 Year
Accepts Healthy Volunteers
No
Eligibility Criteria
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 with ≥25% blasts in the bone marrow (M3), with or without extramedullary disease. Patients with CD19 positive biphenotypic acute leukemia are eligible. Patients with CD19 positive mature B-cell ALL that carry a KMT2Ar 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 does not have a KMT2Ar 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Tanja A Gruber, MD, PhD
Phone
650 723 5535
Email
tagruber@stanford.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Tanja A Gruber, MD, PhD
Organizational Affiliation
Stanford University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Stanford University
City
Palo Alto
State/Province
California
ZIP/Postal Code
94304
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Tanja A Gruber, MD, PhD
Phone
650-723-5535
Email
tagruber@stanford.edu
12. IPD Sharing Statement
Learn more about this trial
TINI 2: Total Therapy for Infants With Acute Lymphoblastic Leukemia II
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