A study of Fludarabine/Cytarabine/Gemtuzumab Ozogamicin with or without Venetoclax in children with recurrent acute myeloid leukemia

ID di studio ICTRP
NCT05183035 (ICTRP)

Titolo ufficiale (approvato dal comitato etico)
A randomized phase 3 trial of fludarabine/cytarabine/gemtuzumab ozogamicin with or without venetoclax in children with relapsed AML (BASEC)

Titolo accademico
A Randomized Phase 3 Trial of Fludarabine/Cytarabine/Gemtuzumab Ozogamicin With or Without Venetoclax in Children With Relapsed AML (ICTRP)

Titolo pubblico
Venetoclax in Children With Relapsed Acute Myeloid Leukemia (AML) (ICTRP)

Malattie studiate
Acute Myeloid Leukemia (ICTRP)

Intervento studiato
Drug: Fludarabine;Drug: Cytarabine;Drug: Gemtuzumab Ozogamicin;Drug: Azacitidine;Drug: Venetoclax (ICTRP)

Tipo di studio
Interventional (ICTRP)

Disegno dello studio
Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label). (ICTRP)

Criteri di inclusione/esclusione
Gender: All
Maximum age: 21 Years
Minimum age: 29 Days
Inclusion Criteria

- Participants must have enrolled on APAL2020SC, NCT Number: NCT04726241 prior to
enrollment on ITCC-101/APAL2020D. (This is only applicable for participants in
USA/Canada/Australia/New Zealand sites/LLS territory).

- Participants must be = 29 days of age and = 21 years of age at enrollment.

- Participants must have one of the following:

1. Children, adolescents, and young adults with AML without demonstrated
FLT3/internal tandem duplication (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.

2. And participants must have AML which is either:

- Untreated second relapse, in participants who are sufficiently fit to
undergo another round of intensive chemotherapy, or

- Untreated first relapse, in participants who cannot tolerate additional
anthracycline containing chemotherapy per investigator discretion.

- Participants must have a performance status corresponding to Eastern Cooperative
Oncology Group (ECOG) scores of 0, 1 or 2 (= 50% Lansky or Karnofsky score).

- Participants must have fully recovered from the acute toxic effects of all prior
anti-cancer therapy and must meet the following minimum duration from prior
anti-cancer directed therapy prior to start of protocol treatment:

1. 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 that can be given up to 24 hours prior to start of
protocol treatment.

2. Intrathecal cytotoxic therapy: No wash-out time is required for participants
having received any combination of intrathecal cytarabine, methotrexate, and/or
hydrocortisone.

3. Antibodies: = 21 days must have elapsed from infusion of last dose of an
antibody-drug conjugate before start of protocol treatment. For unmodified
antibodies or T cell engaging antibodies, 2 half-lives must have elapsed before
start of protocol treatment. Any toxicity related to prior antibody therapy
must be recovered to Grade = 1.

4. Interleukins, Interferons and Cytokines (other than Hematopoietic Growth
Factors): = 21 days after the completion of interleukins, interferon or
cytokines (other than Hematopoietic Growth Factors) before start of protocol
treatment.

5. Hematopoietic growth factors: = 14 days after the last dose of a long-acting
growth factor (e.g., pegfilgrastim) or =7 days for short-acting growth factor
before start of protocol treatment.

6. Radiation therapy (RT) (before start of protocol treatment):

- = 14 days have elapsed for local palliative RT (small port);

- = 84 days must have elapsed if prior craniospinal RT or if = 50% radiation
of pelvis;

- = 42 days must have elapsed if other substantial bone marrow (BM)
radiation.

7. Stem Cell Infusions (before start of protocol treatment):

- = 84 days since allogeneic (non-autologous) bone marrow or stem cell
transplant (with or without total body irradiation [TBI]) or boost
infusion (any stem cell product; not including donor lymphocyte infusion
[DLI]);

- No evidence of active graft versus host disease (GVHD).

8. Participants who are receiving cyclosporine, tacrolimus or other agents to
treat or prevent either graft-versus-host disease post bone marrow transplant
or organ rejection post-transplant are not eligible for this trial.
Participants 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 prior to enrollment.

9. Cellular Therapy: = 42 days after the completion of donor lymphocyte infusion
(DLI) or any type of cellular therapy (e.g., modified T cells, natural killer
[NK] cells, dendritic cells, etc.) before start of protocol treatment.

10. Participants with prior exposure to venetoclax are eligible in this trial.

- Adequate organ function:

1. Adequate Renal Function defined as:

- Creatinine clearance or radioisotope glomerular filtration rate (GFR) =
60ml/min/1.73 m^2, or

- Normal serum creatinine based on age/sex

2. Adequate Liver Function defined as:

- Direct bilirubin < 1.5 x upper limit of normal (ULN), and

- Alkaline phosphatase = 2.5 x ULN, and

- Serum glutamic pyruvic transaminase (SGPT) alanine aminotransferase (ALT)
= 2.5 x ULN. If higher transaminases outside these ranges (up to 5x ULN)
are due to a radiographically identifiable leukemia infiltrate, the
participant will remain eligible. Transaminase elevation up to 5x ULN is
also allowed in case of steatosis on echography.

3. 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
(shortening fraction [SF] < 25% or ejection fraction [EF] < 40%)

- No signs of congestive heart failure at presentation of relapse.

- Participant, parent or guardian must sign and date informed consent and pediatric
assent (when required), prior to the initiation of screening or study specific
procedures, according to local law and legislation.

Exclusion Criteria

- Participants who in the opinion of the investigator may not be able to comply with
the study requirements of the study, are not eligible.

- Participants with Down syndrome.

- Participants with Acute promyelocytic leukemia (APL) or Juvenile myelomonocytic
leukemia (JMML).

- Participants with isolated CNS3 disease or symptomatic CNS3 disease.

- Participants with malabsorption syndrome or any other condition that precludes
enteral administration of venetoclax.

- Participants who are currently receiving an investigational drug other than those
specified for this study.

- Participants with Fanconi anemia, Kostmann syndrome, Shwachman syndrome or any other
known congenital bone marrow failure syndrome.

- Participants with known prior allergy to any of the medications used in protocol
therapy.

- Participants with documented active, uncontrolled infection at the time of study
entry.

- Known hepatitis C virus (HCV), hepatitis B virus (HBV) (known positive hepatitis B
virus (HBV) surface antigen (HBsAg) results), or human immunodeficiency virus (HIV)
infection.

- Concomitant Medications

- Participants who have received strong and moderate CYP3A inducers such as
rifampin, carbama (ICTRP)

non disponibile

Endpoint primari e secondari
Overall Survival (OS) (ICTRP)

Morphology Event Free Survival (EFS);Flow-based Event Free Survival (EFS);Flow-based Overall Response Rate (ORR);Morphological Overall Response Rate (ORR);Duration of Response (DOR);Cumulative Incidence of Relapse (CIR);Disease-related Mortality;Non-disease-related Mortality;Hematopoietic Stem Cell Transplantation (HSCT) Rate;Number of Participants with Adverse Events (AEs);Maximum Observed Plasma Concentration (Cmax) of Venetoclax;Time to Maximum Observed Plasma Concentration (Tmax) of Venetoclax;Area Under the Plasma Concentration-time Curve Over a 24-hour Dose Interval (AUC0-24);Number of Participants That Are Pediatric Minimal Residual Disease (Ped-MRD) Negative with Complete Remission (CR), Partial Complete Remission (CRp), or Complete Remission with Incomplete Hematologic Recovery (CRi);Number of Participants with International Working Group Complete Response (IWG-CR) (ICTRP)

Data di registrazione
21.12.2021 (ICTRP)

Inclusione del primo partecipante
non disponibile

Sponsor secondari
Princess Maxima Center for Pediatric Oncology (European Sponsor);AbbVie;Roche-Genentech;EuPAL (ICTRP)

Contatti aggiuntivi
Seth Karol, MD;Gwen Nichols, MD, gwen.nichols@lls.org, 914-821-8217, St. Jude Children's Research Hospital, (ICTRP)

ID secondari
2021-003212-11, 2023-510160-12-00, ITCC-101/APAL2020D (ICTRP)

Risultati-Dati individuali dei partecipanti
non disponibile

Ulteriori informazioni sullo studio
https://clinicaltrials.gov/ct2/show/NCT05183035 (ICTRP)