A Groupwide Pilot Study to Test the Tolerability and Biologic Activity of the Addition of Azacitidine (IND# 133688, NSC# 102816) to Chemotherapy in Infants With Acute Lymphoblastic Leukemia (ALL) and KMT2A(MLL) Gene Rearrangement
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Enrollment
- 78
- Locations
- 170
- Primary Endpoint
- Tolerability of Azacitidine in Combination With Interfant-06 Standard Chemotherapy in Evaluable Infant Patients With Newly Diagnosed ALL With KMT2A Gene Rearrangement (KMT2A-R). KMT2A Gene Rearrangement (KMT2A-R)
Study Overview
Brief Summary
This pilot phase II trial studies the side effects of azacitidine and combination chemotherapy in infants with acute lymphoblastic leukemia and KMT2A gene rearrangement. Drugs used in chemotherapy, such as methotrexate, prednisolone, daunorubicin hydrochloride, cytarabine, dexamethasone, vincristine sulfate, pegaspargase, hydrocortisone sodium succinate, azacitidine, cyclophosphamide, mercaptopurine, leucovorin calcium, and thioguanine 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. Giving more than one drug may kill more cancer cells.
Detailed Description
PRIMARY OBJECTIVE:
I. To evaluate the tolerability of azacitidine in addition to Interfant-06 standard chemotherapy in infants with newly diagnosed acute lymphoblastic leukemia (ALL) with KMT2A gene rearrangement (KMT2A-R).
SECONDARY OBJECTIVE:
I. To evaluate the biologic activity of azacitidine by pharmacodynamic assessment of global deoxyribonucleic acid (DNA) methylation in peripheral blood mononuclear cells (PBMCs) of infants treated with azacitidine.
EXPLORATORY OBJECTIVES:
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- — to 364 Days (Child)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Infants must be > 36 weeks gestational age at the time of enrollment
- •Patients must have newly diagnosed B lymphoblastic leukemia (2008 World Health Organization [WHO] classification) (also termed B-precursor acute lymphoblastic leukemia) or acute leukemia of ambiguous lineage (ALUL), which includes mixed phenotype acute leukemia (MPAL); for patients with ALUL, the morphology and immunophenotype must be at least 50% B lymphoblastic
- •Central nervous system (CNS) status must be determined based on a sample obtained prior to the administration of any systemic or intrathecal chemotherapy, with the exception of steroid pretreatment
Exclusion Criteria
- •Patients with known absence of KMT2A-rearrangement leukemia prior to enrollment
- •Patients with Down syndrome
- •Patients with secondary B acute lymphoblastic leukemia (B-ALL) that developed after treatment of a prior malignancy with cytotoxic chemotherapy
- •With the exception of steroid pretreatment or the administration of intrathecal methotrexate or intrathecal cytarabine, receipt of any other prior cytotoxic chemotherapy for either the current diagnosis of B-ALL or any cancer diagnosed prior to the initiation of protocol therapy on AALL15P1
Arms & Interventions
Treatment (azacitidine, combination chemotherapy)
See Detailed Description
Intervention: Azacitidine (Drug)
Treatment (azacitidine, combination chemotherapy)
See Detailed Description
Intervention: Biospecimen Collection (Procedure)
Treatment (azacitidine, combination chemotherapy)
See Detailed Description
Intervention: Computed Tomography (Procedure)
Treatment (azacitidine, combination chemotherapy)
See Detailed Description
Intervention: Cyclophosphamide (Drug)
Treatment (azacitidine, combination chemotherapy)
See Detailed Description
Intervention: Cytarabine (Drug)
Treatment (azacitidine, combination chemotherapy)
See Detailed Description
Intervention: Daunorubicin (Drug)
Treatment (azacitidine, combination chemotherapy)
See Detailed Description
Intervention: Daunorubicin Hydrochloride (Drug)
Treatment (azacitidine, combination chemotherapy)
See Detailed Description
Intervention: Dexamethasone (Drug)
Treatment (azacitidine, combination chemotherapy)
See Detailed Description
Intervention: Echocardiography (Procedure)
Treatment (azacitidine, combination chemotherapy)
See Detailed Description
Intervention: Hydrocortisone Sodium Succinate (Drug)
Treatment (azacitidine, combination chemotherapy)
See Detailed Description
Intervention: Leucovorin (Drug)
Treatment (azacitidine, combination chemotherapy)
See Detailed Description
Intervention: Vincristine Sulfate (Drug)
Treatment (azacitidine, combination chemotherapy)
See Detailed Description
Intervention: Leucovorin Calcium (Drug)
Treatment (azacitidine, combination chemotherapy)
See Detailed Description
Intervention: Magnetic Resonance Imaging (Procedure)
Treatment (azacitidine, combination chemotherapy)
See Detailed Description
Intervention: Mercaptopurine (Drug)
Treatment (azacitidine, combination chemotherapy)
See Detailed Description
Intervention: Methotrexate (Drug)
Treatment (azacitidine, combination chemotherapy)
See Detailed Description
Intervention: Multigated Acquisition Scan (Procedure)
Treatment (azacitidine, combination chemotherapy)
See Detailed Description
Intervention: Pegaspargase (Drug)
Treatment (azacitidine, combination chemotherapy)
See Detailed Description
Intervention: Prednisolone (Drug)
Treatment (azacitidine, combination chemotherapy)
See Detailed Description
Intervention: Thioguanine (Drug)
Treatment (azacitidine, combination chemotherapy)
See Detailed Description
Intervention: Vincristine (Drug)
Outcomes
Primary Outcomes
Tolerability of Azacitidine in Combination With Interfant-06 Standard Chemotherapy in Evaluable Infant Patients With Newly Diagnosed ALL With KMT2A Gene Rearrangement (KMT2A-R). KMT2A Gene Rearrangement (KMT2A-R)
Time Frame: 6 months
Proportion of KMT2A-Rearranged patients treated with azacitidine with Dose Limiting Toxicities (DLTs) from the first course of azacitidine administration up to fourth course of azacitidine administration.
Secondary Outcomes
- Biologic Activity, Defined as Global Deoxyribonucleic Acid (DNA) Methylation Change in Peripheral Blood Mononuclear Cells (PBMC)s; Day 1 Prior to Second Course of Azacitidine(Week 13, Day 1 (Following induction phase (5 weeks), the first course of Azacitidine (1 week), and consolidation (6 weeks), the second course of Azacitidine began around Week 13 of therapy))
- Biologic Activity, Defined as Global Deoxyribonucleic Acid (DNA) Methylation Change in Peripheral Blood Mononuclear Cells (PBMC)s; Day 1 Prior to First Course of Azacitidine(Week 6, Day 1 (Following the induction phase (35 days), the first course of Azacitidine began around Week 6 of therapy))
- Biologic Activity, Defined as Global Deoxyribonucleic Acid (DNA) Methylation Change in Peripheral Blood Mononuclear Cells (PBMC)s; Day 5 of Second Course of Azacitidine(Week 13, Day 5 (Following induction phase (5 weeks), the first course of Azacitidine (1 week), and consolidation (6 weeks), the second course of Azacitidine began around Week 13 of therapy))
- Biologic Activity, Defined as Global Deoxyribonucleic Acid (DNA) Methylation Change in Peripheral Blood Mononuclear Cells (PBMC)s; Day 5 of First Course of Azacitidine(Week 6, Day 5 (Following the induction phase (35 days), the first course of Azacitidine began around Week 6 of therapy))