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

NCT05848687 | Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: IRB-68271PEDSHEMALL0015NCI-2023-04129
• Study Type: interventional
• Target: 90
• Locations: 2 countries
• Sites: 24

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.

Conditions

Lymphoblastic Leukemia

Outcome Measures

Primary Outcomes (1)

• Minimal Residual Disease

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

  5 years and 2 months

Secondary Outcomes (3)

• Ziftomenib Minimum safe and Biologically-Effective Dose in Combination with Chemotherapy

  5 years and 6 months

• Event Free Survival

  8 years

• Overall Survival

  8 years

Study Arms (1)

Treatment

EXPERIMENTAL

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; Drug: Mitoxantrone; Drug: PEG asparaginase; Drug: Bortezomib; Drug: Vorinostat; Drug: Mercaptopurine; Drug: Methotrexate; Drug: Blinatumomab; Drug: Ziftomenib

Interventions

Dexamethasone DRUG

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

Treatment

Mitoxantrone DRUG

Given IV

Treatment

PEG asparaginase DRUG

Given IV

Treatment

Bortezomib DRUG

Given IV

Treatment

Vorinostat DRUG

Taken PO or NG

Treatment

Mercaptopurine DRUG

Given PO or NG.

Treatment

Methotrexate DRUG

Given IV, IM or PO

Treatment

Blinatumomab DRUG

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

Treatment

Ziftomenib DRUG

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

Treatment

Eligibility Criteria

• Age: Up to 1 Year
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Kura Oncology, Inc.: collaborator
• United States Department of Defense: collaborator
• Cannonball Kid's Cancer: collaborator
• Tanja Andrea Gruber: lead
• Amgen: collaborator
• The Pediatric Oncology Experimental Therapeutics Investigators' Consortium: collaborator
• Lucile Packard Foundation for Children's Health: collaborator

Study Sites (24)

Phoenix Children's Hospital

Phoenix, Arizona, 85016, United States

RECRUITING

Arkansas Children's Hospital

Little Rock, Arkansas, 72202, United States

RECRUITING

Children's Hospital Los Angeles

Los Angeles, California, 90027, United States

RECRUITING

Valley Children's Hospital

Madera, California, 93636, United States

RECRUITING

Children's Hospital of Orange County

Orange, California, 92868, United States

RECRUITING

Stanford University

Palo Alto, California, 94304, United States

RECRUITING

Rady Children's Hospital San Diego

San Diego, California, 92123, United States

NOT YET RECRUITING

Arnold Palmer Hospital for Children

Orlando, Florida, 32806, United States

RECRUITING

Children's Hospital of Minnesota

Minneapolis, Minnesota, 55404, United States

RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

RECRUITING

Novant Health - Hemby Children's Hospital

Charlotte, North Carolina, 28204, United States

NOT YET RECRUITING

Doernbecher Children's Hospital

Portland, Oregon, 97239, United States

RECRUITING

Penn State Milton S Hershey Medical Center

Hershey, Pennsylvania, 17033-0850, United States

NOT YET RECRUITING

MD Anderson

Houston, Texas, 77030, United States

RECRUITING

University of Texas Health Science Center San Antonio

San Antonio, Texas, 78229, United States

RECRUITING

University of Utah Huntsman Cancer Institute

Salt Lake City, Utah, 84108, United States

NOT YET RECRUITING

Children's Hospital of The King's Daughters

Norfolk, Virginia, 23507, United States

RECRUITING

Alberta Children's Hospital

Calgary, Alberta, T3B 6A8, Canada

NOT YET RECRUITING

Stollery Children's Hospital

Edmonton, Alberta, T6G 2B7, Canada

NOT YET RECRUITING

BC Children's Hospital

Vancouver, British Columbia, V6H 3V4, Canada

NOT YET RECRUITING

McMaster Children's Hospital

Hamilton, Ontario, L8N 3Z5, Canada

NOT YET RECRUITING

CHU Sainte-Justine

Montreal, Quebec, H3T 1C5, Canada

NOT YET RECRUITING

Montreal Children's Hospital

Montreal, Quebec, H4A 3J1, Canada

NOT YET RECRUITING

Chu De Quebec

Québec, Quebec, G1V 4G2, Canada

NOT YET RECRUITING

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

Dexamethasone; Mitoxantrone; pegaspargase; Bortezomib; Vorinostat; Mercaptopurine; Methotrexate; blinatumomab

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Anthraquinones; Anthrones; Anthracenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Quinones; Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Anilides; Amides; Aniline Compounds; Amines; Hydroxamic Acids; Hydroxylamines; Hydroxy Acids; Carboxylic Acids; Sulfhydryl Compounds; Sulfur Compounds; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Aminopterin; Pterins; Pteridines

Study Officials

• Tanja A Gruber, MD, PhD

  Stanford University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Tanja A Gruber, MD, PhD

CONTACT

650 723 5535; tagruber@stanford.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Faculty - Hematology/Oncology

Study Record Dates

• First Submitted: April 27, 2023
• First Posted: May 8, 2023
• Study Start: November 3, 2023
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2033
• Last Updated: April 20, 2026

Record last verified: 2026-04

Locations

US (17); CA (7)