Clinical Trial: Azacitidine and Combination Chemotherapy in Treating Infants With Acute Lymphoblastic Leukemia and KMT2A Gene Rearrangement

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: A Groupwide Pilot Study to Test the Tolerability and Biologic Activity of the Addition of Azacitidine (NSC# 102816) to Chemotherapy in Infants With Acute Lymphoblastic Leukemia (ALL) and KMT2A(MLL) Ge

Brief Summary: This pilot 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 Summary:

PRIMARY OBJECTIVES:

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 OBJECTIVES:

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.

TERTIARY OBJECTIVES:

I. To determine the 5 year event-free survival (EFS) of infants with KMT2A-R treated with azacitidine in addition to Interfant-06 standard chemotherapy.

II. To correlate minimal residual disease (MRD) with outcome in the context of the protocol therapy.

III. To perform pharmacokinetic (PK) testing of azacitidine in infants. IV. To test the expansion of infant T lymphocytes by stimulation with artificial antigen presenting cells identical to those used in chimeric antigen receptor T-cell (CART)-19 production.

V. To collect pharmacodynamic (PD) data for asparaginase activity following pegaspargase administration in infants.

OUTLINE:

INDUCTION CHEMOTHERAPY: Patients receive methotrexate intrathecally (IT) on days 1 and 29, prednisolone orally (PO) or nasogastrically (NG) three times daily (TID) on days 1-7, daunorubicin hydrochloride intravenously (IV) over 1-15 minutes on days 8-9, cytarabine IV over 30 minutes on days 8-21 and IT on day 15, dexamethasone PO,
Sponsor: National Cancer Institute (NCI)

Current Primary Outcome: Incidence of adverse events of azacitidine and combination chemotherapy, graded according to Common Terminology Criteria for Adverse Events 4.0 [ Time Frame: From the first course of azacitidine administration up to fourth course of azacitidine administration ]

Original Primary Outcome: Same as current

Current Secondary Outcome: Biologic activity, defined as global DNA methylation change in PBMCs [ Time Frame: Prior to first course of azacitidine up to day 5 of second course of azacitidine ]

Will calculate the mean long interspersed nucleotide element-1 (LINE-1) methylation for all patients before and after azacitidine and perform paired t-test analysis to determine if there is significant demethylation in the study population for the tested dose level.


Original Secondary Outcome: Same as current

Information By: National Cancer Institute (NCI)

Dates:
Date Received: July 7, 2016
Date Started: March 2017
Date Completion:
Last Updated: April 18, 2017
Last Verified: April 2017