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

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 Overview

• Status: Recruiting
• Conditions: Lymphoblastic Leukemia
• Intervention / Treatment: Drug: Mitoxantrone; Drug: Bortezomib; Drug: Dexamethasone; Drug: Mercaptopurine; Drug: PEG asparaginase; Drug: Vorinostat; Drug: Methotrexate; Drug: Blinatumomab; Drug: Ziftomenib

• Study Type: Interventional
• Enrollment (Estimated): 90
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Tanja A Gruber, MD, PhD; Phone Number: 650 723 5535; Email: tagruber@stanford.edu

Study Locations

• United States
  • California
    • Palo Alto, California, United States, 94304
      • Recruiting
      • Stanford University
      • Contact: Tanja A Gruber, MD, PhD; Phone Number: 650-723-5535; Email: tagruber@stanford.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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: Mitoxantrone; Given IV; Drug: Bortezomib; Given IV; Drug: Dexamethasone; Given orally (PO) or naso-gastrically (NG) or intravenously (IV).; Drug: Mercaptopurine; Given PO or NG.; Drug: PEG asparaginase; Given IV; Drug: Vorinostat; Taken 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Minimal Residual Disease	proportion of patients who are minimal residual disease positive at the end of induction intensification	5 years and 2 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival		8 years
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	5 years and 6 months
Event Free Survival		8 years

Collaborators and Investigators

• Sponsor: Tanja Andrea Gruber
• Collaborators: Amgen; Kura Oncology, Inc.; Pediatric Oncology Experimental Therapeutics Investigators' Consortium; Lucile Packard Foundation for Children's Health
• Investigators: Principal Investigator: Tanja A Gruber, MD, PhD, Stanford University

Study record dates

Study Major Dates

• Study Start (Actual): November 3, 2023
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2033

Study Registration Dates

• First Submitted: April 27, 2023
• First Submitted That Met QC Criteria: April 27, 2023
• First Posted (Actual): May 8, 2023

Study Record Updates

• Last Update Posted (Estimated): February 22, 2024
• Last Update Submitted That Met QC Criteria: February 20, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Dermatologic Agents; Reproductive Control Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Folic Acid Antagonists; Histone Deacetylase Inhibitors; Dexamethasone; Bortezomib; Methotrexate; Asparaginase; Mitoxantrone; Mercaptopurine; Vorinostat; Blinatumomab; Pegaspargase
• Other Study ID Numbers: IRB-68271; PEDSHEMALL0015 (Other Identifier: Stanford OnCore)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No