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
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 153
- 试验地点
- 192
- 主要终点
- Incidence of dose-limiting toxicities (DLTs) (safety phase)
研究概览
简要总结
This phase II trial tests the addition of venetoclax and/or blinatumomab to usual chemotherapy for treating infants with newly diagnosed acute lymphoblastic leukemia (ALL) with a KMT2A gene rearrangement (KMT2A-rearranged [R]) or without a KMT2A gene rearrangement (KMT2A-germline [G]). Venetoclax is in a class of medications called B-cell lymphoma-2 (Bcl-2) inhibitors. It may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Blinatumomab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. Chemotherapy drugs work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Adding venetoclax and/or blinatumomab to standard chemotherapy may be more effective at treating patients with ALL than standard chemotherapy alone, but it may also cause more side effects. This clinical trial evaluates the safety and effectiveness of adding venetoclax and/or blinatumomab to chemotherapy for the treatment of infants with KMT2A-R or KMT2A-G ALL.
详细描述
PRIMARY OBJECTIVES:
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.
SECONDARY OBJECTIVES:
I. To estimate the MRD-negative remission rate for all eligible infants with KMT2A-R ALL treated with venetoclax at the recommended phase 2 dose (RP2D).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- — 至 365 Days（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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 (cumulative prenatal and postnatal age must be > 36 weeks) 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
排除标准
- •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
研究组 & 干预措施
Arm A
See Detailed Description for Arm A.
干预措施: Multigated Acquisition Scan (Procedure)
Arm B, Cohort 4
See Detailed Description for Arm B, Cohort 4.
干预措施: Bone Marrow Aspiration (Procedure)
Arm C
See Detailed Description for Arm C.
干预措施: Prednisone (Drug)
Arm B, Cohort 4
See Detailed Description for Arm B, Cohort 4.
干预措施: Computed Tomography (Procedure)
Arm C
See Detailed Description for Arm C.
干预措施: Daunorubicin (Drug)
Arm A
See Detailed Description for Arm A.
干预措施: Magnetic Resonance Imaging (Procedure)
Arm A
See Detailed Description for Arm A.
干预措施: Mercaptopurine (Drug)
Arm C
See Detailed Description for Arm C.
干预措施: Vincristine (Drug)
Arm A
See Detailed Description for Arm A.
干预措施: Methotrexate (Drug)
Arm A
See Detailed Description for Arm A.
干预措施: Therapeutic Hydrocortisone (Drug)
Arm A
See Detailed Description for Arm A.
干预措施: Thioguanine (Drug)
Arm A
See Detailed Description for Arm A.
干预措施: Vincristine (Drug)
Arm B, Cohort 2
See Detailed Description for Arm B, Cohort 2.
干预措施: Mercaptopurine (Drug)
Arm B, Cohort 1
See Detailed Description for Arm B, Cohort 1.
干预措施: Asparaginase Erwinia chrysanthemi (Drug)
Arm B, Cohort 1
See Detailed Description for Arm B, Cohort 1.
干预措施: Biospecimen Collection (Procedure)
Arm B, Cohort 1
See Detailed Description for Arm B, Cohort 1.
干预措施: Blinatumomab (Biological)
Arm B, Cohort 1
See Detailed Description for Arm B, Cohort 1.
干预措施: Bone Marrow Aspiration (Procedure)
Arm B, Cohort 1
See Detailed Description for Arm B, Cohort 1.
干预措施: Calaspargase Pegol (Drug)
Arm B, Cohort 1
See Detailed Description for Arm B, Cohort 1.
干预措施: Computed Tomography (Procedure)
Arm B, Cohort 1
See Detailed Description for Arm B, Cohort 1.
干预措施: Cyclophosphamide (Drug)
Arm B, Cohort 1
See Detailed Description for Arm B, Cohort 1.
干预措施: Cytarabine (Drug)
Arm B, Cohort 1
See Detailed Description for Arm B, Cohort 1.
干预措施: Daunorubicin (Drug)
Arm B, Cohort 1
See Detailed Description for Arm B, Cohort 1.
干预措施: Dexamethasone (Drug)
Arm B, Cohort 1
See Detailed Description for Arm B, Cohort 1.
干预措施: Echocardiography Test (Procedure)
Arm B, Cohort 1
See Detailed Description for Arm B, Cohort 1.
干预措施: FDG-Positron Emission Tomography (Procedure)
Arm B, Cohort 1
See Detailed Description for Arm B, Cohort 1.
干预措施: Leucovorin (Drug)
Arm B, Cohort 1
See Detailed Description for Arm B, Cohort 1.
干预措施: Levoleucovorin (Drug)
Arm B, Cohort 1
See Detailed Description for Arm B, Cohort 1.
干预措施: Magnetic Resonance Imaging (Procedure)
Arm B, Cohort 1
See Detailed Description for Arm B, Cohort 1.
干预措施: Mercaptopurine (Drug)
Arm B, Cohort 1
See Detailed Description for Arm B, Cohort 1.
干预措施: Methotrexate (Drug)
Arm B, Cohort 1
See Detailed Description for Arm B, Cohort 1.
干预措施: Multigated Acquisition Scan (Procedure)
Arm B, Cohort 1
See Detailed Description for Arm B, Cohort 1.
干预措施: Therapeutic Hydrocortisone (Drug)
Arm B, Cohort 1
See Detailed Description for Arm B, Cohort 1.
干预措施: Thioguanine (Drug)
Arm B, Cohort 1
See Detailed Description for Arm B, Cohort 1.
干预措施: Venetoclax (Drug)
Arm B, Cohort 1
See Detailed Description for Arm B, Cohort 1.
干预措施: Vincristine (Drug)
Arm B, Cohort 2
See Detailed Description for Arm B, Cohort 2.
干预措施: Methotrexate (Drug)
Arm B, Cohort 2
See Detailed Description for Arm B, Cohort 2.
干预措施: Asparaginase Erwinia chrysanthemi (Drug)
Arm B, Cohort 2
See Detailed Description for Arm B, Cohort 2.
干预措施: Biospecimen Collection (Procedure)
Arm B, Cohort 2
See Detailed Description for Arm B, Cohort 2.
干预措施: Multigated Acquisition Scan (Procedure)
Arm B, Cohort 2
See Detailed Description for Arm B, Cohort 2.
干预措施: Blinatumomab (Biological)
Arm B, Cohort 2
See Detailed Description for Arm B, Cohort 2.
干预措施: Bone Marrow Aspiration (Procedure)
Arm B, Cohort 2
See Detailed Description for Arm B, Cohort 2.
干预措施: Calaspargase Pegol (Drug)
Arm B, Cohort 2
See Detailed Description for Arm B, Cohort 2.
干预措施: Computed Tomography (Procedure)
Arm B, Cohort 2
See Detailed Description for Arm B, Cohort 2.
干预措施: Cyclophosphamide (Drug)
Arm B, Cohort 2
See Detailed Description for Arm B, Cohort 2.
干预措施: Cytarabine (Drug)
Arm B, Cohort 2
See Detailed Description for Arm B, Cohort 2.
干预措施: Daunorubicin (Drug)
Arm C
See Detailed Description for Arm C.
干预措施: Thioguanine (Drug)
Arm B, Cohort 2
See Detailed Description for Arm B, Cohort 2.
干预措施: Dexamethasone (Drug)
Arm B, Cohort 2
See Detailed Description for Arm B, Cohort 2.
干预措施: Echocardiography Test (Procedure)
Arm B, Cohort 2
See Detailed Description for Arm B, Cohort 2.
干预措施: FDG-Positron Emission Tomography (Procedure)
Arm B, Cohort 2
See Detailed Description for Arm B, Cohort 2.
干预措施: Leucovorin (Drug)
Arm B, Cohort 2
See Detailed Description for Arm B, Cohort 2.
干预措施: Levoleucovorin (Drug)
Arm A
See Detailed Description for Arm A.
干预措施: Blinatumomab (Biological)
Arm A
See Detailed Description for Arm A.
干预措施: Bone Marrow Aspiration (Procedure)
Arm A
See Detailed Description for Arm A.
干预措施: Calaspargase Pegol (Drug)
Arm A
See Detailed Description for Arm A.
干预措施: Cytarabine (Drug)
Arm A
See Detailed Description for Arm A.
干预措施: Daunorubicin (Drug)
Arm B, Cohort 2
See Detailed Description for Arm B, Cohort 2.
干预措施: Therapeutic Hydrocortisone (Drug)
Arm C
See Detailed Description for Arm C.
干预措施: Doxorubicin (Drug)
Steroid Prephase(prednisone, prednisolone, methylprednisolone)
All patients receive prednisone or prednisolone PO or NG TID or methylprednisolone IV TID for 7 days prior to the start of induction therapy (on days 1-7).
干预措施: Biospecimen Collection (Procedure)
Steroid Prephase(prednisone, prednisolone, methylprednisolone)
All patients receive prednisone or prednisolone PO or NG TID or methylprednisolone IV TID for 7 days prior to the start of induction therapy (on days 1-7).
干预措施: Methylprednisolone (Drug)
Steroid Prephase(prednisone, prednisolone, methylprednisolone)
All patients receive prednisone or prednisolone PO or NG TID or methylprednisolone IV TID for 7 days prior to the start of induction therapy (on days 1-7).
干预措施: Bone Marrow Aspiration (Procedure)
Steroid Prephase(prednisone, prednisolone, methylprednisolone)
All patients receive prednisone or prednisolone PO or NG TID or methylprednisolone IV TID for 7 days prior to the start of induction therapy (on days 1-7).
干预措施: Prednisolone (Drug)
Arm C
See Detailed Description for Arm C.
干预措施: FDG-Positron Emission Tomography (Procedure)
Arm B, Cohort 4
See Detailed Description for Arm B, Cohort 4.
干预措施: Multigated Acquisition Scan (Procedure)
Arm B, Cohort 3
See Detailed Description for Arm B, Cohort 3.
干预措施: FDG-Positron Emission Tomography (Procedure)
Arm B, Cohort 3
See Detailed Description for Arm B, Cohort 3.
干预措施: Lumbar Puncture (Procedure)
Arm B, Cohort 3
See Detailed Description for Arm B, Cohort 3.
干预措施: Calaspargase Pegol (Drug)
Safety Phase Cohort
See Detailed Description for Safety Phase Cohort. (CLOSED TO ACCRUAL 06/03/2026)
干预措施: Multigated Acquisition Scan (Procedure)
Safety Phase Cohort
See Detailed Description for Safety Phase Cohort. (CLOSED TO ACCRUAL 06/03/2026)
干预措施: Echocardiography Test (Procedure)
Safety Phase Cohort
See Detailed Description for Safety Phase Cohort. (CLOSED TO ACCRUAL 06/03/2026)
干预措施: Daunorubicin (Drug)
Arm B, Cohort 4
See Detailed Description for Arm B, Cohort 4.
干预措施: Asparaginase Erwinia chrysanthemi (Drug)
Arm B, Cohort 4
See Detailed Description for Arm B, Cohort 4.
干预措施: Calaspargase Pegol (Drug)
Arm B, Cohort 4
See Detailed Description for Arm B, Cohort 4.
干预措施: Cyclophosphamide (Drug)
Arm B, Cohort 4
See Detailed Description for Arm B, Cohort 4.
干预措施: Daunorubicin (Drug)
Arm B, Cohort 4
See Detailed Description for Arm B, Cohort 4.
干预措施: Dexamethasone (Drug)
Arm B, Cohort 4
See Detailed Description for Arm B, Cohort 4.
干预措施: Leucovorin (Drug)
Arm B, Cohort 3
See Detailed Description for Arm B, Cohort 3.
干预措施: Computed Tomography (Procedure)
Arm A
See Detailed Description for Arm A.
干预措施: FDG-Positron Emission Tomography (Procedure)
Arm B, Cohort 3
See Detailed Description for Arm B, Cohort 3.
干预措施: Echocardiography Test (Procedure)
Arm B, Cohort 4
See Detailed Description for Arm B, Cohort 4.
干预措施: Echocardiography Test (Procedure)
Steroid Prephase(prednisone, prednisolone, methylprednisolone)
All patients receive prednisone or prednisolone PO or NG TID or methylprednisolone IV TID for 7 days prior to the start of induction therapy (on days 1-7).
干预措施: Echocardiography Test (Procedure)
Steroid Prephase(prednisone, prednisolone, methylprednisolone)
All patients receive prednisone or prednisolone PO or NG TID or methylprednisolone IV TID for 7 days prior to the start of induction therapy (on days 1-7).
干预措施: Computed Tomography (Procedure)
Arm B, Cohort 1
See Detailed Description for Arm B, Cohort 1.
干预措施: Lumbar Puncture (Procedure)
Steroid Prephase(prednisone, prednisolone, methylprednisolone)
All patients receive prednisone or prednisolone PO or NG TID or methylprednisolone IV TID for 7 days prior to the start of induction therapy (on days 1-7).
干预措施: FDG-Positron Emission Tomography (Procedure)
Steroid Prephase(prednisone, prednisolone, methylprednisolone)
All patients receive prednisone or prednisolone PO or NG TID or methylprednisolone IV TID for 7 days prior to the start of induction therapy (on days 1-7).
干预措施: Multigated Acquisition Scan (Procedure)
Steroid Prephase(prednisone, prednisolone, methylprednisolone)
All patients receive prednisone or prednisolone PO or NG TID or methylprednisolone IV TID for 7 days prior to the start of induction therapy (on days 1-7).
干预措施: Lumbar Puncture (Procedure)
Arm B, Cohort 3
See Detailed Description for Arm B, Cohort 3.
干预措施: Thioguanine (Drug)
Arm B, Cohort 4
See Detailed Description for Arm B, Cohort 4.
干预措施: Levoleucovorin (Drug)
Arm B, Cohort 3
See Detailed Description for Arm B, Cohort 3.
干预措施: Mercaptopurine (Drug)
Arm B, Cohort 3
See Detailed Description for Arm B, Cohort 3.
干预措施: Venetoclax (Drug)
Safety Phase Cohort
See Detailed Description for Safety Phase Cohort. (CLOSED TO ACCRUAL 06/03/2026)
干预措施: Cytarabine (Drug)
Safety Phase Cohort
See Detailed Description for Safety Phase Cohort. (CLOSED TO ACCRUAL 06/03/2026)
干预措施: Asparaginase Erwinia chrysanthemi (Drug)
Safety Phase Cohort
See Detailed Description for Safety Phase Cohort. (CLOSED TO ACCRUAL 06/03/2026)
干预措施: Blinatumomab (Biological)
Safety Phase Cohort
See Detailed Description for Safety Phase Cohort. (CLOSED TO ACCRUAL 06/03/2026)
干预措施: Calaspargase Pegol (Drug)
Arm C
See Detailed Description for Arm C.
干预措施: Calaspargase Pegol (Drug)
Safety Phase Cohort
See Detailed Description for Safety Phase Cohort. (CLOSED TO ACCRUAL 06/03/2026)
干预措施: Magnetic Resonance Imaging (Procedure)
Safety Phase Cohort
See Detailed Description for Safety Phase Cohort. (CLOSED TO ACCRUAL 06/03/2026)
干预措施: Lumbar Puncture (Procedure)
Arm C
See Detailed Description for Arm C.
干预措施: Leucovorin (Drug)
Arm B, Cohort 3
See Detailed Description for Arm B, Cohort 3.
干预措施: Biospecimen Collection (Procedure)
Arm B, Cohort 3
See Detailed Description for Arm B, Cohort 3.
干预措施: Bone Marrow Aspiration (Procedure)
Arm C
See Detailed Description for Arm C.
干预措施: Levoleucovorin (Drug)
Arm B, Cohort 3
See Detailed Description for Arm B, Cohort 3.
干预措施: Dexamethasone (Drug)
Safety Phase Cohort
See Detailed Description for Safety Phase Cohort. (CLOSED TO ACCRUAL 06/03/2026)
干预措施: Thioguanine (Drug)
Arm B, Cohort 3
See Detailed Description for Arm B, Cohort 3.
干预措施: Cytarabine (Drug)
Arm B, Cohort 3
See Detailed Description for Arm B, Cohort 3.
干预措施: Levoleucovorin (Drug)
Arm B, Cohort 4
See Detailed Description for Arm B, Cohort 4.
干预措施: Mercaptopurine (Drug)
Arm B, Cohort 4
See Detailed Description for Arm B, Cohort 4.
干预措施: Venetoclax (Drug)
Arm B, Cohort 4
See Detailed Description for Arm B, Cohort 4.
干预措施: Therapeutic Hydrocortisone (Drug)
Arm B, Cohort 3
See Detailed Description for Arm B, Cohort 3.
干预措施: Cyclophosphamide (Drug)
Arm B, Cohort 3
See Detailed Description for Arm B, Cohort 3.
干预措施: Daunorubicin (Drug)
Arm B, Cohort 3
See Detailed Description for Arm B, Cohort 3.
干预措施: Blinatumomab (Biological)
Arm B, Cohort 4
See Detailed Description for Arm B, Cohort 4.
干预措施: Methotrexate (Drug)
Arm B, Cohort 4
See Detailed Description for Arm B, Cohort 4.
干预措施: Thioguanine (Drug)
Arm B, Cohort 4
See Detailed Description for Arm B, Cohort 4.
干预措施: Vincristine (Drug)
Arm C
See Detailed Description for Arm C.
干预措施: Blinatumomab (Biological)
Steroid Prephase(prednisone, prednisolone, methylprednisolone)
All patients receive prednisone or prednisolone PO or NG TID or methylprednisolone IV TID for 7 days prior to the start of induction therapy (on days 1-7).
干预措施: Prednisone (Drug)
Arm C
See Detailed Description for Arm C.
干预措施: Cytarabine (Drug)
Arm C
See Detailed Description for Arm C.
干预措施: Cyclophosphamide (Drug)
Arm C
See Detailed Description for Arm C.
干预措施: Dexamethasone (Drug)
Arm C
See Detailed Description for Arm C.
干预措施: Magnetic Resonance Imaging (Procedure)
Safety Phase Cohort
See Detailed Description for Safety Phase Cohort. (CLOSED TO ACCRUAL 06/03/2026)
干预措施: Bone Marrow Aspiration (Procedure)
Arm A
See Detailed Description for Arm A.
干预措施: Asparaginase Erwinia chrysanthemi (Drug)
Safety Phase Cohort
See Detailed Description for Safety Phase Cohort. (CLOSED TO ACCRUAL 06/03/2026)
干预措施: Computed Tomography (Procedure)
Safety Phase Cohort
See Detailed Description for Safety Phase Cohort. (CLOSED TO ACCRUAL 06/03/2026)
干预措施: FDG-Positron Emission Tomography (Procedure)
Arm A
See Detailed Description for Arm A.
干预措施: Computed Tomography (Procedure)
Arm A
See Detailed Description for Arm A.
干预措施: Echocardiography Test (Procedure)
Arm A
See Detailed Description for Arm A.
干预措施: Leucovorin (Drug)
Arm C
See Detailed Description for Arm C.
干预措施: Prednisolone (Drug)
Arm B, Cohort 3
See Detailed Description for Arm B, Cohort 3.
干预措施: Vincristine (Drug)
Arm C
See Detailed Description for Arm C.
干预措施: Methotrexate (Drug)
Arm B, Cohort 3
See Detailed Description for Arm B, Cohort 3.
干预措施: Therapeutic Hydrocortisone (Drug)
Arm B, Cohort 3
See Detailed Description for Arm B, Cohort 3.
干预措施: Methotrexate (Drug)
Arm B, Cohort 3
See Detailed Description for Arm B, Cohort 3.
干预措施: Leucovorin (Drug)
Arm A
See Detailed Description for Arm A.
干预措施: Cyclophosphamide (Drug)
Arm A
See Detailed Description for Arm A.
干预措施: Levoleucovorin (Drug)
Safety Phase Cohort
See Detailed Description for Safety Phase Cohort. (CLOSED TO ACCRUAL 06/03/2026)
干预措施: Cyclophosphamide (Drug)
Safety Phase Cohort
See Detailed Description for Safety Phase Cohort. (CLOSED TO ACCRUAL 06/03/2026)
干预措施: Leucovorin (Drug)
Safety Phase Cohort
See Detailed Description for Safety Phase Cohort. (CLOSED TO ACCRUAL 06/03/2026)
干预措施: Levoleucovorin (Drug)
Arm C
See Detailed Description for Arm C.
干预措施: Therapeutic Hydrocortisone (Drug)
Arm B, Cohort 2
See Detailed Description for Arm B, Cohort 2.
干预措施: Thioguanine (Drug)
Safety Phase Cohort
See Detailed Description for Safety Phase Cohort. (CLOSED TO ACCRUAL 06/03/2026)
干预措施: Biospecimen Collection (Procedure)
Arm B, Cohort 4
See Detailed Description for Arm B, Cohort 4.
干预措施: FDG-Positron Emission Tomography (Procedure)
Arm B, Cohort 4
See Detailed Description for Arm B, Cohort 4.
干预措施: Lumbar Puncture (Procedure)
Arm C
See Detailed Description for Arm C.
干预措施: Lumbar Puncture (Procedure)
Arm A
See Detailed Description for Arm A.
干预措施: Lumbar Puncture (Procedure)
Arm C
See Detailed Description for Arm C.
干预措施: Methylprednisolone (Drug)
Steroid Prephase(prednisone, prednisolone, methylprednisolone)
All patients receive prednisone or prednisolone PO or NG TID or methylprednisolone IV TID for 7 days prior to the start of induction therapy (on days 1-7).
干预措施: Magnetic Resonance Imaging (Procedure)
Safety Phase Cohort
See Detailed Description for Safety Phase Cohort. (CLOSED TO ACCRUAL 06/03/2026)
干预措施: Methotrexate (Drug)
Arm C
See Detailed Description for Arm C.
干预措施: Multigated Acquisition Scan (Procedure)
Safety Phase Cohort
See Detailed Description for Safety Phase Cohort. (CLOSED TO ACCRUAL 06/03/2026)
干预措施: Therapeutic Hydrocortisone (Drug)
Arm C
See Detailed Description for Arm C.
干预措施: Bone Marrow Aspiration (Procedure)
Arm C
See Detailed Description for Arm C.
干预措施: Computed Tomography (Procedure)
Arm C
See Detailed Description for Arm C.
干预措施: Echocardiography Test (Procedure)
Arm B, Cohort 4
See Detailed Description for Arm B, Cohort 4.
干预措施: Cytarabine (Drug)
Arm C
See Detailed Description for Arm C.
干预措施: Biospecimen Collection (Procedure)
Arm C
See Detailed Description for Arm C.
干预措施: Mercaptopurine (Drug)
Safety Phase Cohort
See Detailed Description for Safety Phase Cohort. (CLOSED TO ACCRUAL 06/03/2026)
干预措施: Vincristine (Drug)
Arm B, Cohort 3
See Detailed Description for Arm B, Cohort 3.
干预措施: Asparaginase Erwinia chrysanthemi (Drug)
Arm B, Cohort 2
See Detailed Description for Arm B, Cohort 2.
干预措施: Venetoclax (Drug)
Safety Phase Cohort
See Detailed Description for Safety Phase Cohort. (CLOSED TO ACCRUAL 06/03/2026)
干预措施: Mercaptopurine (Drug)
Arm B, Cohort 2
See Detailed Description for Arm B, Cohort 2.
干预措施: Magnetic Resonance Imaging (Procedure)
Arm B, Cohort 2
See Detailed Description for Arm B, Cohort 2.
干预措施: Lumbar Puncture (Procedure)
Arm B, Cohort 4
See Detailed Description for Arm B, Cohort 4.
干预措施: Biospecimen Collection (Procedure)
Arm A
See Detailed Description for Arm A.
干预措施: Dexamethasone (Drug)
Arm B, Cohort 4
See Detailed Description for Arm B, Cohort 4.
干预措施: Blinatumomab (Biological)
Safety Phase Cohort
See Detailed Description for Safety Phase Cohort. (CLOSED TO ACCRUAL 06/03/2026)
干预措施: Dexamethasone (Drug)
Arm A
See Detailed Description for Arm A.
干预措施: Biospecimen Collection (Procedure)
Arm B, Cohort 3
See Detailed Description for Arm B, Cohort 3.
干预措施: Magnetic Resonance Imaging (Procedure)
Arm B, Cohort 3
See Detailed Description for Arm B, Cohort 3.
干预措施: Multigated Acquisition Scan (Procedure)
Arm B, Cohort 4
See Detailed Description for Arm B, Cohort 4.
干预措施: Magnetic Resonance Imaging (Procedure)
Safety Phase Cohort
See Detailed Description for Safety Phase Cohort. (CLOSED TO ACCRUAL 06/03/2026)
干预措施: Venetoclax (Drug)
Arm B, Cohort 2
See Detailed Description for Arm B, Cohort 2.
干预措施: Vincristine (Drug)
结局指标
主要结局
Incidence of dose-limiting toxicities (DLTs) (safety phase)
时间窗: For the duration of the induction + venetoclax cycle
For the safety phase, DLTs of the induction + venetoclax cycle of KMT2A-rearranged (R) patients will be assessed.
Incidence of DLTs (expansion phase)
时间窗: During the induction, consolidation, and MARMA cycles of Arm B
For the expansion phase, DLTs of Arm B will be assessed and monitored for the cycles that contain venetoclax (induction, consolidation, and MARMA cycles of Arm B).
Minimal residual disease (MRD)-negative remission rate
时间窗: At the end of induction
The end of induction MRD-negative remission rate will be compared between Arm A and Arm B. MRD negativity is defined as achievement of complete remission and MRD \< 0.01% by flow cytometry. The MRD-negative remission rate at the end of induction between Arm A and Arm B will be compared using a one-sided Z test of proportions with Type I error of 0.15.
次要结局
- Event free survival (EFS) rates of infants with KMT2A-R ALL(From date of randomization to treatment failure, first documented relapse following achievement of remission-1, occurrence of a second or secondary malignant neoplasm, or death, assessed up to 3 years)
- MRD-negative remission rate(At the end of induction)
- 3-year EFS of infants with KMT2A-R ALL(From date of randomization to treatment failure, first documented relapse following achievement of remission-1, occurrence of a second or secondary malignant neoplasm, or death, assessed up to 3 years)
- Proportion of KMT2A-germline (G) patients in Arm C who are able to receive all treatment cycles before maintenance(Up to interim maintenance 2)
- 3-year EFS of infants with KMT2A-G ALL treated on Arm C(From date of enrollment to treatment failure, first documented relapse following achievement of remission-1, occurrence of a second or secondary malignant neoplasm, or death, assessed up to 3 years)
- Pharmacokinetics (PK) of venetoclax in infants(On days 7, 10, and 14 of induction)