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

Status unconfirmed · Phase 1/Phase 2

Conditions studied: AML, Childhood

In brief

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

Key facts

Study ID

NCT03825367

Run by

Therapeutic Advances in Childhood Leukemia Consortium

People needed

13

Starts

2019-11-29

Expected to finish

2024-03-30

Last updated by the study team

2022-10-12

Who can join

Age: 1 and older, up to 30. Sex: any. Healthy volunteers: not accepted.

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.
• 1st 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.
• Cytoreduction with hydroxyurea Hydroxyurea can be initiated and continued for up to 24 hours prior to the start of day 1 nivolumab and azacytidine. It is recommended to use hydroxyurea in patients with significant leukocytosis (WBC > 50,000/L) to control blast count before initiation of systemic protocol therapy.
• B. Hematopoietic stem cell transplant: Patients who have experienced their relapse after a HSCT are eligible provided they have no evidence of active GVHD, no past history of grade 3 or greater GVHD, and are at least 100 days post-transplant at the time of enrollment. Patients should be off immune suppression for at least 2 weeks (excluding physiologic replacement steroids).
• C. Hematopoietic growth factors: It must have been at least 7 days since the completion of therapy with GCSF or other growth factors at the time of enrollment. It must have been at least 14 days since the completion of therapy with pegfilgrastim (Neulasta®).
• D. Biologic (anti-neoplastic agent): At least 7 days after the last dose of a biologic agent. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur. The duration of this interval must be discussed with the study chair
• E. Monoclonal antibodies: At least 3 half-lives of the antibody must have elapsed after the last dose of monoclonal antibody. (i.e. Gemtuzumab = 36 days)
• F. Immunotherapy: At least 42 days after the completion of any type of immunotherapy, e.g. tumor vaccines or CAR T-cells.
• G. XRT: XRT is prohibited during protocol therapy. No washout period is necessary for radiation given to non-CNS chloromas; ≥ 90 days must have elapsed if prior TBI or craniospinal XRT.
• Renal and hepatic function
• Patients must have adequate renal and hepatic functions as indicated by the following laboratory values:
• A. Adequate renal function defined as: Patient must have a calculated creatinine clearance or radioisotope GFR ≥ 70ml/min/1.73m2 OR a normal serum creatinine based on age/gender in the chart below:

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).

Where it is running

• Children's Hospital of Los Angeles — Los Angeles, California, United States
• Children's Healthcare of Atlanta — Atlanta, Georgia, United States
• Johns Hopkins University — Baltimore, Maryland, United States
• Columbia University Medical Center — New York, New York, United States
• Levine Cancer Institute — Charlotte, North Carolina, United States
• Cincinnati Children's Hospital Medical Center — Cincinnati, Ohio, United States
• St. Jude Children's Research Hospital — Memphis, Tennessee, United States
• Children's Health — Dallas, Texas, United States
• Cook Children's Medical Center — Fort Worth, Texas, United States
• Texas Children's Hospital/Baylor College of Medicine — Houston, Texas, United States
• Primary Children's Hospital — Salt Lake City, Utah, United States
• Seattle Children's Hospital — Seattle, Washington, United States

Full record on ClinicalTrials.gov

Trial information comes from ClinicalTrials.gov and is refreshed daily. TrialsForMe does not provide medical care and does not run the studies it lists.