Overview

Venetoclax in Children With Relapsed Acute Myeloid Leukemia (AML)

Status:
Not yet recruiting
Trial end date:
2032-02-01
Target enrollment:
0
Participant gender:
All
Summary
A study to evaluate if the randomized addition of venetoclax to a chemotherapy backbone (fludarabine/cytarabine/gemtuzumab ozogamicin [GO]) improves survival of children/adolescents/young adults with acute myeloid leukemia (AML) in 1st relapse who are unable to receive additional anthracyclines, or in 2nd relapse.
Phase:
Phase 3
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
LLS PedAL Initiative, LLC
Collaborators:
AbbVie
EuPAL
Princess Maxima Center for Pediatric Oncology (European Sponsor)
Roche-Genentech
Treatments:
Azacitidine
Cytarabine
Fludarabine
Gemtuzumab
Venetoclax
Criteria
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:

- Children, adolescents, and young adults with acute myeloid leukemia without
FLT3/internal tandem duplication (ITD) mutation in:

1. Second relapse, who are sufficiently fit to undergo another round of
intensive chemotherapy

2. First relapse who per investigator discretion cannot tolerate additional
anthracycline containing chemotherapy.

- 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 liver abnormality is due to radiographically identifiable
leukemia infiltrate, the participant will remain eligible.

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 another investigational drug (GO is not
considered investigational in 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.

- No known human immunodeficiency virus (HIV) infection.

- Post menarchal female participants with positive pregnancy test.

- Concomitant Medications

- Participants 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.

- Participants who have consumed grapefruit, grapefruit products, Seville oranges
(including marmalade containing Seville oranges) or starfruit within 3 days of
the start of study treatment.

- Participants who have hypersensitivity to the active substance or to any of the
excipients listed in summary of product characteristics (SPC).

- Pregnancy or Breast-Feeding:

- Participants who are pregnant or breast-feeding.

- Participants of reproductive potential may not participate unless they have
agreed to use a highly effective contraceptive method per clinical trials
facilitation group (CTFG) guidelines for the duration of study therapy and for 6
months after the completion of all study therapy.

- Male participants 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
for 4 months after the completion of all study therapy.

Additional criteria to receive a gemtuzumab ozogamicin infusion:

Gemtuzumab ozogamicin should not be given:

- to participants with history of veno-occlusive disease (VOD)/Sinusoidal obstruction
syndrome (SOS) grade 4

- to participants with history of VOD/SOS grade 3

- to participants with CD33 negative leukemic blasts (determined at local lab)

Note that these participants are eligible for the study but will not be treated with
gemtuzumab ozogamicin.