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

• ClinicalTrials.gov Identifier: NCT05848687
• Recruitment Status: Recruiting
• First Posted: May 8, 2023
• Last Update Posted: February 22, 2024
• Sponsor: Tanja Andrea Gruber
• Collaborators: Pediatric Oncology Experimental Therapeutics Investigators' Consortium; Amgen; Lucile Packard Foundation for Children's Health; Kura Oncology, Inc.
• Information provided by (Responsible Party): Tanja Andrea Gruber, Stanford University

Tracking Information

• First Submitted Date: April 27, 2023
• First Posted Date: May 8, 2023
• Last Update Posted Date: February 22, 2024
• Actual Study Start Date: November 3, 2023
• Estimated Primary Completion Date: December 2028 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 27, 2023)

Minimal Residual Disease [ Time Frame: 5 years and 2 months ]

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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: April 27, 2023)

• Ziftomenib Maximum Tolerated Dose in Combination with Chemotherapy [ Time Frame: 5 years and 6 months ]
  determine the estimated maximum tolerated dose of Ziftomenib in combination with chemotherapy, on the basis of observed DLTs
• Event Free Survival [ Time Frame: 8 years ]
• Overall Survival [ Time Frame: 8 years ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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
• 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 Provided
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Lymphoblastic Leukemia

Intervention

• 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

Study Arms

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

Interventions:

• Drug: Dexamethasone
• Drug: Mitoxantrone
• Drug: PEG asparaginase
• Drug: Bortezomib
• Drug: Vorinostat
• Drug: Mercaptopurine
• Drug: Methotrexate
• Drug: Blinatumomab
• Drug: Ziftomenib

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: April 27, 2023): 90
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 2033
• Estimated Primary Completion Date: December 2028 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: up to 1 Year (Child)
• Accepts Healthy Volunteers: No

Contacts

Contact: Tanja A Gruber, MD, PhD; 650 723 5535; tagruber@stanford.edu

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05848687
• Other Study ID Numbers: IRB-68271; PEDSHEMALL0015 ( Other Identifier: Stanford OnCore )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Tanja Andrea Gruber, Stanford University
• Original Responsible Party: Stanford University
• Current Study Sponsor: Tanja Andrea Gruber
• Original Study Sponsor: Stanford University

Collaborators

• Pediatric Oncology Experimental Therapeutics Investigators' Consortium
• Amgen
• Lucile Packard Foundation for Children's Health
• Kura Oncology, Inc.

Investigators

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

• PRS Account: Stanford University
• Verification Date: February 2024