Nivolumab in Combination With 5-azacytidine in Childhood Relapsed/Refractory AML

NCT03825367 | Unknown Phase 1 DMC FDA Drug

• 1 other identifier: T2016-002
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 12

Brief Summary

This is a phase I/II Study of Nivolumab in Combination with 5-azacytidine in pediatric patients with relapsed/refractory acute myeloid leukemia

Conditions

AML, Childhood

Keywords

Relapse; Refractory; Leukemia; Acute; Pediatric; nivolumab; azacytidine

Outcome Measures

Primary Outcomes (2)

• Dose Toxicity

  Occurrence of dose limiting toxicity (DLT) during Cycle 1 of therapy (Phase I)

  4 weeks

• Remission

  Achievement of complete remission (CR/CRp/CRi) at the end of cycle 1

  4 weeks

Study Arms (1)

Open label design

OTHER

Nivolumab and 5-azacytidine,

Drug: Nivolumab; Drug: 5-azacytidine

Interventions

Nivolumab DRUG

The dose of Nivolumab will be 3 mg/kg which is the adult recommended dose and is the recommended dose in children in the phase 2 portion of COG ADVL1412. If 3 mg/kg is not tolerated in combination with 5-azacytidine, the dose will be stepped down to 1 mg/kg.

Open label design

5-azacytidine DRUG

75mg/m2 subcutaneously will be given daily for 7 days on days 1 to 7.

Open label design

Eligibility Criteria

• Age: 1 Year - 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Age Patients must be ≥ 1 and ≤30 years of age.
• Diagnosis
• Relapsed or refractory AML with ≥5% blasts (by morphology) in the bone marrow.
• st or greater relapse, OR
• Failed to go into remission (i.e. refractory) after first or greater relapse, OR
• Failed to go into remission from original diagnosis after two or more induction attempts.
• Relapsed or refractory AML with ≤ 5% blasts (by morphology) and MRD positive disease (M1/MRD+): Two serial marrows demonstrating stable or rising MRD ≥ 0.1 % (i.e. not declining). MRD will be determined by multiparameter flow cytometry using AML-associated phenotype markers, or real-time quantitative PCR for AML-associated genetic lesions
• Patients may have CNS 1 or 2 or other sites of extramedullary disease. No cranial irradiation is allowed during the protocol therapy.
• Patients with secondary AML are eligible.
• Patients with DNA fragility syndromes (such as Fanconi anemia, Bloom syndrome) are excluded.
• Patients with Down Syndrome will be eligible and will be included as an observation cohort
• Performance Level Karnofsky \> 50% for patients \> 16 years of age and Lansky \> 50% for patients ≤ 16 years of age.
• Prior Therapy Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study.
• A. Myelosuppressive chemotherapy
• Prior chemotherapy Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study. At least 14 days must have elapsed since the completion of the cytotoxic therapy, except Intrathecal chemotherapy.

You may not qualify if:

• Patients will be excluded if they have a known allergy or hypersensitivity to nivolumab or AZA used in the study.
• Patients will be excluded if they have a systemic fungal, bacterial, viral or other infection that is exhibiting ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics or other treatment. The patient needs to be off pressors and have negative blood cultures for 48 hours.
• Patients will be excluded if there is a plan to administer non-protocol chemotherapy, radiation therapy, or immunotherapy during the study period.
• Patients will be excluded if they have significant concurrent disease, illness, psychiatric disorder or social issue that would compromise patient safety or compliance with the protocol treatment or procedures, interfere with consent, study participation, follow up, or interpretation of study results.
• Patients with DNA fragility syndromes (such as Fanconi anemia, Bloom syndrome) are excluded.
• Patients with a known history of severe interstitial lung disease or severe pneumonitis or active pneumonitis that is uncontrolled in the opinion of the treating physician.
• Patients who have previously been treated with nivolumab will be excluded.
• Patients with a known history of any of the following autoimmune diseases are excluded: (a) patients with a history of inflammatory bowel disease (including Crohn's disease and ulcerative colitis) (b) patients with a history of rheumatoid arthritis, systemic progressive sclerosis \[scleroderma\], Systemic Lupus Erythematosus, autoimmune vasculitis \[e.g., Wegener's Granulomatosis\]).
• Patients with organ allografts (such as renal transplant) are excluded.
• Patients with known Human Immunodeficiency Virus seropositivity will be excluded.
• Known to be positive for hepatitis B by surface antigen expression. Known to have active hepatitis C infection (positive by polymerase chain reaction or on antiviral therapy for hepatitis C within the last 6 months).
• Pregnant or breastfeeding.
• Acute promyelocytic leukemia (APL).
• CNS 3 disease.
• Patients who have experienced their relapse after a HSCT and are less than 100 days post-transplant at the time of enrollment, have active GVHD at time of enrollment, have past history of grade 3 or greater GVHD, Patients on immune suppression (excluding physiologic replacement steroids).

Sponsors & Collaborators

• Therapeutic Advances in Childhood Leukemia Consortium: lead
• Bristol-Myers Squibb: collaborator

Study Sites (12)

Children's Hospital of Los Angeles

Los Angeles, California, 90027, United States

Location

Children's Healthcare of Atlanta

Atlanta, Georgia, 30322, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21287, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Levine Cancer Institute

Charlotte, North Carolina, 28204, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

Children's Health

Dallas, Texas, 75235, United States

Location

Cook Children's Medical Center

Fort Worth, Texas, 76104, United States

Location

Texas Children's Hospital/Baylor College of Medicine

Houston, Texas, 77030, United States

Location

Primary Children's Hospital

Salt Lake City, Utah, 84108, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98101, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Recurrence; Leukemia

Interventions

Nivolumab; Azacitidine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 28, 2019
• First Posted: January 31, 2019
• Study Start: November 29, 2019
• Primary Completion: May 31, 2023
• Study Completion: March 30, 2024
• Last Updated: October 12, 2022

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (12)