A Phase 2 Study of Blinatumomab in Combination With Chemotherapy for Infants With Newly Diagnosed Acute Lymphoblastic Leukemia With Randomization of KMT2A-Rearranged Patients to Addition of Venetoclax
A Phase 2 Study of Blinatumomab in Combination with Chemotherapy for Infants with Newly Diagnosed Acute Lymphoblastic Leukemia with Randomization of KMT2A-Rearranged Patients to Addition of Venetoclax
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Clinical Trial Information
Trial Contact: Jones, Jamie; Parker, Melanie; Armatti, Julie M; Singh, Sarah H; Torrescano, Tanner; Frankos, Marie
Trial Phone: 3218412008 ; 321-843-1036 ; 321-843-5284 ; 321.841.7561 ; 321-841-8271 ; 321-842-8738
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IRB No: C25.187.07
Protocol Abbrev: AALL2321
Principal Investigator: Jaime H Mercado, MD
Phase: Drug: Phase II
Age Group: Pediatric
Treatment: Drug: Asparaginase Erwinia chrysanthemi Procedure: Biospecimen Collection Biological: Blinatumomab Procedure: Bone Marrow Aspiration Drug: Calaspargase Pegol Procedure: Computed Tomography Drug: Cyclophosphamide Drug: Cytarabine Drug: Daunorubicin Drug: Dexamethasone Drug: Doxorubicin Procedure: Echocardiography Test Procedure: FDG-Positron Emission Tomography Drug: Leucovorin Drug: Levoleucovorin Procedure: Lumbar Puncture Procedure: Magnetic Resonance Imaging Drug: Mercaptopurine Drug: Methotrexate Drug: Methylprednisolone Procedure: Multigated Acquisition Scan Drug: Prednisolone Drug: Prednisone Drug: Therapeutic Hydrocortisone Drug: Thioguanine Drug: Venetoclax Drug: Vincristine
Therapies Involved: Chemotherapy
ClinicalTrials.gov ID: NCT06317662
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Objective
I. To evaluate the safety and tolerability of venetoclax in addition to a standard chemotherapy backbone and two cycles of blinatumomab in infants (aged 365 days or less at diagnosis) with newly diagnosed KMT2A-R ALL.
II. To determine in a randomized manner if the addition of venetoclax to induction chemotherapy improves end of induction minimal residual disease (MRD)-negative remission rates in infants with KMT2A-R ALL. -
Key Eligibility
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
