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

Sponsor
Stanford University (Other)
Overall Status
Not yet recruiting
CT.gov ID
NCT05848687
Collaborator
Pediatric Oncology Experimental Therapeutics Investigators' Consortium (Other), Amgen (Industry), Lucile Packard Children's Hospital Foundation (Other)
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125
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Study Details

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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
90 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
TINI 2: Total Therapy for Infants With Acute Lymphoblastic Leukemia II
Anticipated Study Start Date :
Jul 1, 2023
Anticipated Primary Completion Date :
Dec 1, 2028
Anticipated Study Completion Date :
Dec 1, 2033

Arms and Interventions

Arm Intervention/Treatment
Experimental: Treatment

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

Drug: Dexamethasone
Given orally (PO) or naso-gastrically (NG) or intravenously (IV).

Drug: Mitoxantrone
Given IV

Drug: PEG asparaginase
Given IV

Drug: Bortezomib
Given IV

Drug: Vorinostat
Taken PO or NG

Drug: Mercaptopurine
Given PO or NG.

Drug: Methotrexate
Given IV, IM or PO

Drug: Blinatumomab
Will be administered at 15 mcg/m2/day for 28 days following induction and reinduction

Drug: Ziftomenib
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

Outcome Measures

Primary Outcome Measures

  1. Minimal Residual Disease [5 years and 2 months]

    proportion of patients who are minimal residual disease positive at the end of induction intensification

Secondary Outcome Measures

  1. Ziftomenib Maximum Tolerated Dose in Combination with Chemotherapy [5 years and 6 months]

    determine the estimated maximum tolerated dose of Ziftomenib in combination with chemotherapy, on the basis of observed DLTs

  2. Event Free Survival [8 years]

  3. Overall Survival [8 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:
1 Year and Older
Sexes Eligible for Study:
All
Accepts 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 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

Contacts and Locations

Locations

Site City State Country Postal Code
1 Stanford University Palo Alto California United States 94304

Sponsors and Collaborators

  • Stanford University
  • Pediatric Oncology Experimental Therapeutics Investigators' Consortium
  • Amgen
  • Lucile Packard Children's Hospital Foundation

Investigators

  • Principal Investigator: Tanja A Gruber, MD, PhD, Stanford University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Stanford University
ClinicalTrials.gov Identifier:
NCT05848687
Other Study ID Numbers:
  • IRB-68271
  • PEDSHEMALL0015
First Posted:
May 8, 2023
Last Update Posted:
May 8, 2023
Last Verified:
Apr 1, 2023
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:

Study Results

No Results Posted as of May 8, 2023