Acute myeloid leukemia bone marrow cancer
Conditions
Interventions
This is an open-label randomized phase 3 study. Patients receiving venetoclax
will receive adult equivalent dosages, either based on age (less than 2 years)
or weight (2 years and older), unless dos
Sponsors
Prinses Máxima Centrum voor Kinderoncologie
Eligibility
Age
No minimum to 64 Years
Inclusion criteria
Inclusion criteria: Patient must have the following: a. Children, adolescents, and young adults with acute myeloid leukemia without demonstrated FLT3/ITD mutation. Ideally, the status of the mutation needs to be proven in the current relapse. Nevertheless, patients with previous FLT3/ITD negative test from prior lines can be included based on local results in order to not delay the start of treatment. b. And patients must have AML which is either: - untreated second relapse, in patients who are sufficiently fit to undergo another round of intensive chemotherapy, or - untreated first relapse, in patients who cannot tolerate additional anthracycline containing chemotherapy per investigator discretion. Patients must have a performance status corresponding to ECOG scores of 0, 1 or 2 (>= 50% Lansky or Karnofsky score) Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy and must meet the minimum duration from prior anti-cancer directed therapy prior to enrolment (more details in the protocol). Cytotoxic chemotherapy: Must not have received cytotoxic chemotherapy within 14 days prior to start of protocol treatment, except for corticosteroids, low dose cytarabine or hydroxyurea (see below) that can be given up to 24 hours prior to start of protocol treatment. Antibodies: >= 21 days must have elapsed from infusion of last dose of an antibody-drug conjugate prior to start of protocol treatment. Interleukins, Interferons and Cytokines : >= 21 days after the completion of interleukins, interferon or cytokines Hematopoietic growth factors: >= 14 days after the last dose of a longacting growth factor or >=7 days for short-acting growth factor prior to start of protocol treatment. Radiation therapy (RT): Between 14 and 84 days depeding on the extent of radiation fields Stem Cell Infusions: >= 84 days since allogeneic bone marrow or stem cell transplant or boost infusion. No evidence of active graft versus host disease Patients must be off medications to treat or prevent either graft-versushost disease post bone marrow transplant or organ rejection posttransplant for at least 14 days Cellular Therapy: >= 42 days after the completion of any type of cellular Therapy Adequate organ function. a. Adequate Renal Function defined as: • Calculated eGFR (based on Schwartz formula) or radioisotope GFR >= 60ml/min/1.73 m2, OR •A serum creatinine based on age/sex b. Adequate Liver Function defined as: •Total or direct (conjugated) bilirubin
Exclusion criteria
Exclusion criteria: D5a. In het Engels 1) General exclusion criteria a. Patients who in the opinion of the investigator, may not be able to comply with the study requirements of the study, are not eligible. b. Patients with Down syndrome. c. Patients with Acute promyelocytic leukemia (APL) or Juvenile myelomonocytic leukemia (JMML). d. Patients with isolated CNS3 disease or symptomatic CNS3 disease. e. Patients with malabsorption syndrome or any other condition that precludes enteral administration of venetoclax. f. Patients who are currently receiving another investigational drug other than those specified for this study (venetoclax and GO are considered investigational in this study). g. Patients with Fanconi anemia, Kostmann syndrome, Shwachman syndrome or any other known congenital bone marrow failure syndrome. h. Patients with known prior allergy to any of the medications used in protocol therapy. i. Patients with documented active, uncontrolled infection at the time of study entry. j. Known hepatitis C virus (HCV), hepatitis B virus (HBV) (known positive hepatitis B virus (HBV) surface antigen (HBsAg) result) or human immunodeficiency virus (HIV) infection. Note: For the countries under EU CTR, these tests are required at screening. For other countries, HCV, HBV, and HIV testing does not need to be conducted at screening unless it is required per local guidelines or local regulations. 2) Concomitant Medications a. Patients who have received strong and moderate CYP3A inducers such as rifampin, carbamazepine, phenytoin, and St. John*s wort within 7 days of the start of protocol treatment. b. Patients who have consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges) or starfruit within 3 days of the start of protocol treatment. c. Patients who are hypersensitive to the active substance or to any of the excipients listed in the summary of products characteristics (SPC) or US prescribing information per local label. 3) Pregnancy or Breast-Feeding: a. Patients who are pregnant or breast-feeding. b. Patients of reproductive potential may not participate unless they have agreed to use a highly effective contraceptive method per Clinical Trial Facilitation Group (CTFG) guidelines for the duration of study therapy at least 30 days after last dose of venetoclax, or 7 months after gemtuzumab ozogamicin treatment, or for 6 months after the completion of all study therapy, whichever is longer c. Male patients must use a condom during intercourse and agree not to father a child or donate sperm during therapy and for the duration of study therapy and at least 30 days after last dose of venetoclax or 4 months after last dose of gemtuzumab ozogamicin, 6 months from the last dose of cytarabine, or 90 days after last exposure to any other chemotherapy, whichever is longer. Gemtuzumab ozogamicin should not be given: • to patients with history of veno-occlusive disease (VOD)/Sinusoidal obstruction syndrome (SOS) grade 3 or 4 • to patients with CD33 negative leukemic blasts (determined at local lab) These patients are eligible for the study but will not be treated with gemtuzumab ozogamicin.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary endpoint of the study is overall survival (OS). OS is defined as time from randomization until death of any cause. Patients still alive at the time of clinical cutoff date will be censored at their last known alive date. | — |
Secondary
| Measure | Time frame |
|---|---|
| Morphology and flow-based event-free survival (EFS): days from date of randomization to the first event (subsequent relapse after ped-flow and ped-morph CR, death of any cause, failure to achieve remission (ped-flow and ped-morph CR, CRp or CRi) after 2 cycles of treatment, or secondary malignancy). Patients who are event-free will be censored at date of last adequate disease assessment. Pediatric flow and morphologic treatment failure (defined by morphology and flow as not achieving remission after two cycles in separate analyses) is calculated as an event at day 1. Flow-based overall response rate (ORR) Morphological ORR Duration of response (DOR): Time from documentation of disease response (ped-flow CR/CRp/CRri or ped-morph CR/CRp/CRi) to disease progression or death of disease, whichever occurs earlier. Cumulative incidence of relapse (CIR): Estimate of the risk that a patient will develop a relapse during a specified period of time. Non-relapse mortality (NRM): Death without recurrence or progression of disease during treatment. Hematopoietic stem cell transplantation (HSCT) rate: The rate of those proceeding to subsequent hematopoietic stem cell transplantation as consolidation therapy is calculated as the number of patients who receive a hematopoietic stem cell infusion divided by the total number of patients enrolled. Safety Pharmacokinetics (PK) of venetoclax in blood in combination with intensive chemotherapy and GO. Pediatric Minimal Residual Disease (Ped-MRD) negative ped-flow is defined as patients obtaining ORR (CR/CRp/CRri: ) CR/CRp/CRi with no detectable residual disease defines asand | — |
Countries
Netherlands
Outcome results
None listed