Testing the Addition of the Anti-cancer Drug Venetoclax and/or the Anti-cancer Immunotherapy Blinatumomab to the Usual Chemotherapy Treatment for Infants With Newly Diagnosed KMT2A-rearranged or KMT2A-non-rearranged Leukemia

Launched by NATIONAL CANCER INSTITUTE (NCI) · Mar 16, 2024

Keywords

ClinConnect Summary

This clinical trial is studying whether adding two specific anti-cancer treatments, called venetoclax and blinatumomab, to the usual chemotherapy can help infants with a type of leukemia known as acute lymphoblastic leukemia (ALL). This trial focuses on infants who have just been diagnosed with either KMT2A-rearranged or KMT2A-non-rearranged ALL. Venetoclax works by blocking a protein that helps cancer cells survive, while blinatumomab may help the immune system fight the cancer. Researchers want to find out if using these drugs together with standard chemotherapy is more effective than chemotherapy alone, even though it might also cause more side effects.

To participate in this trial, infants must be newly diagnosed with B-acute lymphoblastic leukemia and be 365 days old or younger. They should also meet specific health criteria and have consent from a parent or guardian. Participants can expect to receive regular chemotherapy along with the new treatments being tested, and the study will monitor their health to see how well these combinations work. It's important to note that this trial is not yet recruiting participants, so it will start at a later date.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • All patients must be enrolled on APEC14B1 and consented to eligibility screening (part A) prior to treatment and enrollment on AALL2321
• • Infants (aged 365 days or less) on the date of diagnosis are eligible; infants must be \> 36 weeks gestational age at the time of enrollment
• • Patients must have newly diagnosed B-acute lymphoblastic leukemia (B-ALL, 2017 World Health Organization \[WHO\] classification), also termed B-precursor ALL, or acute leukemia of ambiguous lineage (ALAL), which includes mixed phenotype acute leukemia. For patients with ALAL, the immunophenotype of the leukemia must comprise at least 50% B lineage
• • Diagnostic immunophenotype: Leukemia cells must express CD19
• Exclusion Criteria:
• • Patients with Down Syndrome
• • Patients with secondary B-ALL that developed after treatment of a prior malignancy with cytotoxic chemotherapy
• * Patients must not have received any cytotoxic chemotherapy for either the current diagnosis of infant ALL or for any cancer diagnosis prior to the initiation of protocol therapy, with the exception of:
• * Steroid pretreatment:
• • PredniSONE, prednisoLONE, or methylPREDNISolone for ≤ 72 hours (3 days) in the 7 days prior to enrollment. The dose of predniSONE, prednisoLONE or methylPREDNISolone does not affect eligibility
• • Inhaled and topical steroids are not considered pretreatment
• • Note: Pretreatment with dexamethasone in the 28 days prior to initiation of protocol therapy is not allowed with the exception of a single dose of dexamethasone used during or within 6 hours prior to or after sedation to prevent or treat airway edema. However, prior exposure to ANY steroids that occurred \> 28 days before enrollment does not affect eligibility
• * Intrathecal cytarabine or methotrexate:
• • An intrathecal dose of cytarabine or methotrexate in the 7 days prior to enrollment does not affect eligibility
• • Note: The preference is to defer the diagnostic lumbar puncture with intrathecal chemotherapy to day 1 of induction to allow for cytoreduction of circulating blasts and decrease the potential for central nervous system (CNS) contamination due to a traumatic tap. If done prior to day 1 of induction, these results will be used to determine CNS status
• * Hydroxyurea:
• • Pretreatment with ≤ 72 hours (3 days) of hydroxyurea in the 7 days prior to enrollment does not affect eligibility
• • All patients and/or their parents or legal guardians must sign a written informed consent
• • All institutional, Food and Drug Administration (FDA) and National Cancer Institute (NCI) requirements for human studies must be met