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AML, ChildhoodPhase 1/2NCT03825367

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

A Phase 1/2 study testing Nivolumab and 5-azacytidine in people with AML, Childhood, run by Therapeutic Advances in Childhood Leukemia Consortium at 12 sites in United States.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

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

Who is it for?
Ages 1 year to 30 years
Conditions the study is for
AML, Childhood
What is being tested?
Nivolumab and 5-azacytidine
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
13 participants
Where
12 sitesUnited States
Study dates
29 Nov 2019to 30 Mar 2024
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 1 year to 30 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • 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.
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  • 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.
  • 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.
  • 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).
  • 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®).
  • 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
  • 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)
  • Immunotherapy: At least 42 days after the completion of any type of immunotherapy, e.g. tumor vaccines or CAR T-cells.
  • 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:
  • 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:
  • Adequate Liver Function Defined as: Direct bilirubin < 1.5 x upper limit of normal (ULN) for age or normal, AND alanine transaminase (ALT) < 5 x ULN for age. The hepatic requirements are waived for patients with known or suspected liver involvement by leukemia. This must be reviewed by and approved by the study chair or vice chair.
  • Adequate Cardiac Function Defined as: Shortening fraction of ≥ 27% OR ejection fraction of ≥ 50%.
  • Reproductive Function A. Female patients of childbearing potential must have a negative urine or serum pregnancy test confirmed within 24 hours prior to first dose.
  • Female patients with infants must agree not to breastfeed their infants while on this study.
  • Male and female patients of child-bearing potential must agree to use an effective method of contraception approved by the investigator during the study and for a minimum of 7 months after study treatment. Women of childbearing potential (WOCBP) receiving nivolumab will be instructed to adhere to contraception for a period of 5 months after the last dose of nivolumab. Men receiving nivolumab and who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 7 months after the last dose of nivolumab.
  • Informed Consent Patients and/or their parents or legal guardians must be capable of understanding the investigational nature, potential risks and benefits of the study. All patients and/or their parents or legal guardians must sign a written informed consent. Age appropriate assent will be obtained per institutional guidelines. To allow non-English speaking patients to participate in this study, bilingual health services will be provided in the appropriate language when feasible.
  • Protocol Approval All institutional, FDA, and OHRP requirements for human studies must be met.

Who cannot join

  • 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.
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  • 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).

Trial locations and contacts

12 sites in 1 country.

12 sites in 1 country

United States12 sites

  • Children's Healthcare of Atlanta

    Atlanta, Georgia, 30322

  • Johns Hopkins University

    Baltimore, Maryland, 21287

  • Levine Cancer Institute

    Charlotte, North Carolina, 28204

  • Cincinnati Children's Hospital Medical Center

    Cincinnati, Ohio, 45229

  • Children's Health

    Dallas, Texas, 75235

  • Cook Children's Medical Center

    Fort Worth, Texas, 76104

  • Texas Children's Hospital/Baylor College of Medicine

    Houston, Texas, 77030

  • Children's Hospital of Los Angeles

    Los Angeles, California, 90027

  • St. Jude Children's Research Hospital

    Memphis, Tennessee, 38105

  • Columbia University Medical Center

    New York, New York, 10032

  • Primary Children's Hospital

    Salt Lake City, Utah, 84108

  • Seattle Children's Hospital

    Seattle, Washington, 98101

Other trials in United States

About this study

Official title: A Phase I/II Study of Nivolumab in Combination With 5-azacytidine in Pediatric Patients With Relapsed/Refractory Acute Myeloid Leukemia (BMS Reference CA209-9JY)

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

Read the detailed description

This proposed study will be the first to test nivolumab in combination with AZA in pediatric patients with hematologic malignancies. Patients will receive the first dose of nivolumab on day 1 along with AZA. After "chemotherapy priming", a second dose of nivolumab will be given at day 15 which will enhance the effect of nivolumab on the regenerating CD4+ and CD8+ memory T cells.

To establish a recommended Phase II dose (RP2D)of nivolumab in combination with 5-azacytidine in children with relapsed or refractory AML. To assess the clinical activity of Nivolumab in combination with 5-azacytidine in AML patients with M2/M3 disease at study entry.

Conditions
AML, Childhood
Being tested
Nivolumab, 5-azacytidine
Keywords
Relapse, Refractory, Leukemia, Acute, Pediatric, nivolumab, azacytidine
Medical subject headings
Leukemia, Myeloid, Acute, Recurrence, Leukemia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • NivolumabDrug

    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.

  • 5-azacytidineDrug

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

Study groups in NCT03825367
Study groupRoleWhat they receive
Open label designOtherNivolumab and 5-azacytidine,
Receives: Drug: Nivolumab; Drug: 5-azacytidine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Dose Toxicity

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

    Measured: 4 weeks

  2. Remission

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

    Measured: 4 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 Jan 2019
  2. Study start29 Nov 2019
  3. Primary completion31 May 2023 (estimated)
  4. Study completion30 Mar 2024 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
13 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03825367
Sponsor's protocol ID
T2016-002
Status last verified
Oct 2022
First submitted
28 Jan 2019
Last updated
12 Oct 2022
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Nivolumab and 5-azacytidine in people with AML, Childhood, run by Therapeutic Advances in Childhood Leukemia Consortium at 12 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 32 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 12 Oct 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 12 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Dose Toxicity (time frame: 4 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03825367.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Oct 2022.

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