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Venetoclax in children with relapsed AML
EU CTIS ID: 2023-510160-12-00
What this study is testing
To assess if venetoclax combined with FLA+GO (fludarabine, high-dose cytarabine, and gemtuzumab ozogamicin) will improve overall survival of children with relapsed acute myeloid leukemia (AML) compared to FLA+GO.
- Therapeutic confirmatory (Phase III)
A plain-language read of the study's public EU CTIS listing. The study team confirms the details.
Who can take part
You may be able to join if
- 1. 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.
- 10. Patients must be off medications to treat or prevent either graft-versus- host disease post bone marrow transplant or organ rejection post- transplant for at least 14 days.
- 11. Cellular Therapy: ≥ 42 days after the completion of any type of cellular therapy.
- 12. 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 ≤ 1.5xULN, AND •Alkaline phosphatase ≤ 2.5xULN, AND •SGPT (ALT) ≤ 2.5xULN o if higher transaminases outside these ranges (up to 5x ULN) are due to a radiographically identifiable leukemia infiltrate, the patient will remain eligible. Transaminase elevation up to 5x ULN is also allowed in case of steatosis on echography. c.Cardiac performance: Minimum cardiac function defined as: •No history of congestive heart failure in need of medical treatment •No pre-treatment diminished left ventricular function on echocardiography (FS <25% or EF <40%) •No signs of congestive heart failure at presentation of relapse
- 13. Informed consent: Patient, parent or legal guardian must sign and date informed consent and pediatric assent (when required), prior to the initiation of screening or study specific procedures.
- 2. Patients must have a performance status corresponding to ECOG scores of 0, 1 or 2 (≥ 50% Lansky or Karnofsky score)
You likely can't join if
- 1. Patients who in the opinion of the investigator may not be able to comply with the study requirements of the study, are not eligible.
- 10. 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 not under EU CTR, HCV, HBV, and HIV testing does not need to be conducted at screening unless it is required per local guidelines or local regulations.
- 11. Concomitant Medications - 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 study treatment. - Patients who have consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges) or starfruit within 3 days of the start of study treatment. - Patients who are hypersensitive to the active substance or to any of the excipients listed in SPC.
- 12. Pregnancy or Breast-Feeding: - Patients who are pregnant or breast-feeding. - Patients of reproductive potential may not participate unless they have agreed to use a highly effective contraceptive method per CTFG guidelines for the duration of study therapy and 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. - 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.
- 13. Gemtuzumab ozogamicin should not be given: - to patients with history of veno-occlusive disease (VOD/SOS)/ 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.
- 2. Patients with Down syndrome.
See the full eligibility criteria
Who can join
- 1. 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.
- 10. Patients must be off medications to treat or prevent either graft-versus- host disease post bone marrow transplant or organ rejection post- transplant for at least 14 days.
- 11. Cellular Therapy: ≥ 42 days after the completion of any type of cellular therapy.
- 12. 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 ≤ 1.5xULN, AND •Alkaline phosphatase ≤ 2.5xULN, AND •SGPT (ALT) ≤ 2.5xULN o if higher transaminases outside these ranges (up to 5x ULN) are due to a radiographically identifiable leukemia infiltrate, the patient will remain eligible. Transaminase elevation up to 5x ULN is also allowed in case of steatosis on echography. c.Cardiac performance: Minimum cardiac function defined as: •No history of congestive heart failure in need of medical treatment •No pre-treatment diminished left ventricular function on echocardiography (FS <25% or EF <40%) •No signs of congestive heart failure at presentation of relapse
- 13. Informed consent: Patient, parent or legal guardian must sign and date informed consent and pediatric assent (when required), prior to the initiation of screening or study specific procedures.
- 2. Patients must have a performance status corresponding to ECOG scores of 0, 1 or 2 (≥ 50% Lansky or Karnofsky score)
- 3. 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).
- 4. 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.
- 5. Antibodies: ≥ 21 days must have elapsed from infusion of last dose of an antibody-drug conjugate prior to start of protocol treatment.
- 6. Interleukins, Interferons and Cytokines : ≥ 21 days after the completion of interleukins, interferon or cytokines.
- 7. Hematopoietic growth factors: ≥ 14 days after the last dose of a long- acting growth factor or ≥7 days for short-acting growth factor prior to start of protocol treatment.
- 8. Radiation therapy (RT): Between 14 and 84 days depeding on the extent of radiation fields.
- 9. Stem Cell Infusions: ≥ 84 days since allogeneic bone marrow or stem cell transplant or boost infusion. No evidence of active graft versus host disease.
What rules you out
- 1. Patients who in the opinion of the investigator may not be able to comply with the study requirements of the study, are not eligible.
- 10. 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 not under EU CTR, HCV, HBV, and HIV testing does not need to be conducted at screening unless it is required per local guidelines or local regulations.
- 11. Concomitant Medications - 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 study treatment. - Patients who have consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges) or starfruit within 3 days of the start of study treatment. - Patients who are hypersensitive to the active substance or to any of the excipients listed in SPC.
- 12. Pregnancy or Breast-Feeding: - Patients who are pregnant or breast-feeding. - Patients of reproductive potential may not participate unless they have agreed to use a highly effective contraceptive method per CTFG guidelines for the duration of study therapy and 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. - 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.
- 13. Gemtuzumab ozogamicin should not be given: - to patients with history of veno-occlusive disease (VOD/SOS)/ 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.
- 2. Patients with Down syndrome.
- 3. Patients with Acute promyelocytic leukemia (APL) or Juvenile myelomonocytic leukemia (JMML).
- 4. Patients with isolated CNS3 disease or symptomatic CNS3 disease.
- 5. Patients with malabsorption syndrome or any other condition that precludes enteral administration of venetoclax.
- 6. 1.6 Patients who are currently receiving an investigational drug other than those specified for this study (Venetoclax, Fludarabine, Cytarabine, GO and Azacitidine are considered investigational in this study in the countries under EU CTR. For other countries not under EU CTR, please refer to section 9).
- 7. Patients with Fanconi anemia, Kostmann syndrome, Shwachman syndrome or any other known congenital bone marrow failure syndrome.
- 8. Patients with known prior allergy to any of the medications used in protocol therapy.
- 9. Patients with documented active, uncontrolled infection at the time of study entry.
The study team makes the final eligibility decision.
Where it's taking place
- New Zealand
- Japan
- Canada
- Israel
- United States
- Australia
- United Kingdom
- Switzerland
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 0-17 years, 18-64 years. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include New Zealand; Japan; Canada; Israel; United States; Australia and 2 more location(s). Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.