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

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT02828358
• Collaborator: (none)
• Enrollment: 78
• Locations: 174
• Arm: 1
• Anticipated Duration (Months): 93.2
• Patients Per Site: 0.4
• Patients Per Site Per Month: 0

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Acute Leukemia of Ambiguous Lineage; B Acute Lymphoblastic Leukemia; Mixed Phenotype Acute Leukemia	Drug: Azacitidine; Drug: Cyclophosphamide; Drug: Cytarabine; Drug: Daunorubicin; Drug: Daunorubicin Hydrochloride; Drug: Dexamethasone; Drug: Hydrocortisone Sodium Succinate; Other: Laboratory Biomarker Analysis; Drug: Leucovorin; Drug: Leucovorin Calcium; Drug: Mercaptopurine; Drug: Methotrexate; Drug: Pegaspargase; Other: Pharmacological Study; Drug: Prednisolone; Drug: Thioguanine; Drug: Vincristine; Drug: Vincristine Sulfate	Phase 2

Detailed Description

PRIMARY OBJECTIVE:

1. 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:

1. 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:

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

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

3. 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.

4. 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, NG, or IV TID on days 8-28, vincristine sulfate IV over 1 minute on days 8, 15, 22, and 29, pegaspargase IV over 1-2 hours or intramuscularly (IM) on day 12, and hydrocortisone sodium succinate IT on days 15 and 29 in the absence of disease progression or unacceptable toxicity. Only patients with KMT2A-R continue to post-induction chemotherapy.

POST-INDUCTION CHEMOTHERAPY:

AZACITIDINE BLOCK I: Prior to CONSOLIDATION, patients receive azacitidine IV over 10-40 minutes daily for 5 days in the absence of disease progression or unacceptable toxicity.

CONSOLIDATION: Following completion of AZACITIDINE BLOCK I, patients receive cyclophosphamide IV over 30-60 minutes on days 1 and 29, mercaptopurine PO or NG daily on days 1-28, cytarabine IV or subcutaneously (SC) daily on days 3-6, 10-13, 17-20, and 24-27 and IT on day 10, methotrexate IT on day 24, and hydrocortisone sodium succinate IT on days 10 and 24 in the absence of disease progression or unacceptable toxicity.

AZACITIDINE BLOCK II: Prior to INTERIM MAINTENANCE, patients receive azacitidine as in AZACITIDINE BLOCK I

INTERIM MAINTENANCE: Following completion of AZACITIDINE BLOCK II, patients receive mercaptopurine PO or NG daily on days 1-14, methotrexate IV over 24 hours on days 1 and 8 and IT on days 2 and 9, leucovorin calcium PO or IV on days 3-4 and 10-11, hydrocortisone sodium succinate IT on days 2 and 9, cytarabine IV over 3 hours every 12 hours on days 15-16 and 22-23 for a total of 8 doses, and pegaspargase IV over 1-2 hours or IM on day 23 in the absence of disease progression or unacceptable toxicity.

AZACITIDINE BLOCK III: Prior to DELAYED INTENSIFICATION PART I, patients receive azacitidine as in AZACITIDINE BLOCK I.

DELAYED INTENSIFICATION PART I: Following completion of AZACITIDINE BLOCK III, patients receive pegaspargase IV over 1-2 hours or IM on day 1, dexamethasone PO, NG, or IV TID on days 1-14 and 15-21 with a taper on days 15-21, thioguanine PO or NG daily on days 1-28, vincristine sulfate IV over 1 minute on days 1, 8, 15, and 22, daunorubicin hydrochloride IV over 1-15 minutes on days 1, 8, 15, and 22, cytarabine IV or SC on days 2-5, 9-12, 16-19, and 23-26 and IT on days 1 and 15, and hydrocortisone sodium succinate IT on days 1 and 15 in the absence of disease progression or unacceptable toxicity.

AZACITIDINE BLOCK IV: Prior to DELAYED INTENSIFICATION PART II, patients receive azacitidine as in AZACITIDINE BLOCK I.

DELAYED INTENSIFICATION PART II: Following completion of AZACITIDINE BLOCK IV, patients receive thioguanine PO or NG daily on days 1-14, cyclophosphamide IV over 15-30 minutes on days 1 and 15, cytarabine IV or SC on days 2-5 and 9-12 in the absence of disease progression or unacceptable toxicity.

MAINTENANCE: Following DELAYED INTENSIFICATION PART II, patients receive mercaptopurine PO or NG on days 1-168, methotrexate IT on day 1 and 92 and PO once weekly on days 8-91 and 98-168, hydrocortisone sodium succinate IT on day 1, 57, and 99, and cytarabine IT on day 57. Starting on day 169, patients receive mercaptopurine PO or NG on days 1-84 and methotrexate PO once weekly. Cycles repeat every 84 days for 2 years from the start of INDUCTION CHEMOTHERAPY in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up periodically.

Study Design

• Study Type: Interventional
• Actual Enrollment: 78 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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) Gene Rearrangement
• Actual Study Start Date: Mar 27, 2017
• Actual Primary Completion Date: Sep 30, 2020
• Anticipated Study Completion Date: Dec 31, 2024

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Treatment (azacitidine, combination chemotherapy) See Detailed Description

Drug: Azacitidine; Given IV; Other Names: 5 AZC 5-AC 5-Azacytidine 5-AZC Azacytidine Azacytidine, 5- Ladakamycin Mylosar Onureg U-18496 Vidaza ; Drug: Cyclophosphamide; Given IV; Other Names: (-)-Cyclophosphamide 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate Carloxan Ciclofosfamida Ciclofosfamide Cicloxal Clafen Claphene CP monohydrate CTX CYCLO-cell Cycloblastin Cycloblastine Cyclophospham Cyclophosphamid monohydrate Cyclophosphamide Monohydrate Cyclophosphamidum Cyclophosphan Cyclophosphane Cyclophosphanum Cyclostin Cyclostine Cytophosphan Cytophosphane Cytoxan Fosfaseron Genoxal Genuxal Ledoxina Mitoxan Neosar Revimmune Syklofosfamid WR- 138719 ; Drug: Cytarabine; Given IV, SC, IT; Other Names: .beta.-Cytosine arabinoside 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone 1-.beta.-D-Arabinofuranosylcytosine 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone 1-Beta-D-arabinofuranosylcytosine 1.beta.-D-Arabinofuranosylcytosine 2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl- 2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl- Alexan Ara-C ARA-cell Arabine Arabinofuranosylcytosine Arabinosylcytosine Aracytidine Aracytin Aracytine Beta-Cytosine Arabinoside CHX-3311 Cytarabinum Cytarbel Cytosar Cytosine Arabinoside Cytosine-.beta.-arabinoside Cytosine-beta-arabinoside Erpalfa Starasid Tarabine PFS U 19920 U-19920 Udicil WR-28453 ; Drug: Daunorubicin; Given IV; Other Names: Daunomycin Daunorrubicina DNR Leukaemomycin C Rubidomycin Rubomycin C ; Drug: Daunorubicin Hydrochloride; Given IV; Other Names: Cerubidin Cerubidine Cloridrato de Daunorubicina Daunoblastin Daunoblastina Daunoblastine Daunomycin Hydrochloride Daunomycin, hydrochloride Daunorubicin.HCl Daunorubicini Hydrochloridum FI-6339 Ondena RP-13057 Rubidomycin Hydrochloride Rubilem ; Drug: Dexamethasone; Given PO, NG, IV; Other Names: Aacidexam Adexone Aknichthol Dexa Alba-Dex Alin Alin Depot Alin Oftalmico Amplidermis Anemul mono Auricularum Auxiloson Baycadron Baycuten Baycuten N Cortidexason Cortisumman Decacort Decadrol Decadron Decadron DP Decalix Decameth Decasone R.p. Dectancyl Dekacort Deltafluorene Deronil Desamethasone Desameton Dexa-Mamallet Dexa-Rhinosan Dexa-Scheroson Dexa-sine Dexacortal Dexacortin Dexafarma Dexafluorene Dexalocal Dexamecortin Dexameth Dexamethasone Intensol Dexamethasonum Dexamonozon Dexapos Dexinoral Dexone Dinormon Dxevo Fluorodelta Fortecortin Gammacorten Hemady Hexadecadrol Hexadrol Lokalison-F Loverine Methylfluorprednisolone Millicorten Mymethasone Orgadrone Spersadex TaperDex Visumetazone ZoDex ; Drug: Hydrocortisone Sodium Succinate; Given IT; Other Names: (11beta)-21-(3-Carboxy-1-oxopropyl)-11,17-dihydroxypregn-4-ene-3,20-dione, Monosodium Salt A-Hydrocort Buccalsone Corlan Cortisol Sodium Succinate Cortop Efcortelan Emergent-EZ Flebocortid Hidroc Clora Hycorace Hydro-Adreson Hydrocort Hydrocortisone 21-Sodium Succinate Hydrocortisone Na Succinate Kinogen Nordicort Nositrol Sinsurrene Sodium hydrocortisone succinate Solu-Cortef Solu-Glyc ; Other: Laboratory Biomarker Analysis; Correlative studies; Drug: Leucovorin; Given PO, IV; Other Names: Folinic acid ; Drug: Leucovorin Calcium; Given PO, IV; Other Names: Adinepar Calcifolin Calcium (6S)-Folinate Calcium Folinate Calcium Leucovorin Calfolex Calinat Cehafolin Citofolin Citrec Citrovorum Factor Cromatonbic Folinico Dalisol Disintox Divical Ecofol Emovis Factor, Citrovorum Flynoken A Folaren Folaxin FOLI-cell Foliben Folidan Folidar Folinac Folinate Calcium folinic acid Folinic Acid Calcium Salt Pentahydrate Folinoral Folinvit Foliplus Folix Imo Lederfolat Lederfolin Leucosar leucovorin Rescufolin Rescuvolin Tonofolin Wellcovorin ; Drug: Mercaptopurine; Given PO, NG; Other Names: 3H-Purine-6-thiol 6 MP 6 Thiohypoxanthine 6 Thiopurine 6-Mercaptopurine 6-Mercaptopurine Monohydrate 6-MP 6-Purinethiol 6-Thiopurine 6-Thioxopurine 6H-Purine-6-thione, 1,7-dihydro- (9CI) 7-Mercapto-1,3,4,6-tetrazaindene Alti-Mercaptopurine Azathiopurine Bw 57-323H Flocofil Ismipur Leukerin Leupurin Mercaleukim Mercaleukin Mercaptina Mercaptopurinum Mercapurin Mern NCI-C04886 Puri-Nethol Purimethol Purine, 6-mercapto- Purine-6-thiol (8CI) Purine-6-thiol, monohydrate Purinethiol Purinethol U-4748 WR-2785 ; Drug: Methotrexate; Given IT, IV, PO; Other Names: Abitrexate Alpha-Methopterin Amethopterin Brimexate CL 14377 CL-14377 Emtexate Emthexat Emthexate Farmitrexat Fauldexato Folex Folex PFS Lantarel Ledertrexate Lumexon Maxtrex Medsatrexate Metex Methoblastin Methotrexate LPF Methotrexate Methylaminopterin Methotrexatum Metotrexato Metrotex Mexate Mexate-AQ MTX Novatrex Rheumatrex Texate Tremetex Trexeron Trixilem WR-19039 ; Drug: Pegaspargase; Given IV; Other Names: L-Asparaginase with Polyethylene Glycol Oncaspar Oncaspar-IV PEG-Asparaginase PEG-L-Asparaginase PEG-L-Asparaginase (Enzon - Kyowa Hakko) PEGLA Polyethylene Glycol L-Asparaginase Polyethylene Glycol-L-Asparaginase ; Other: Pharmacological Study; Correlative studies; Drug: Prednisolone; Given PO, NG; Other Names: (11beta)-11,17,21-Trihydroxypregna-1,4-diene-3,20-dione .delta.1-Hydrocortisone Adnisolone Aprednislon Capsoid Cortalone Cortisolone Dacortin H Decaprednil Decortin H Delta(1)Hydrocortisone Delta- Cortef Delta-Cortef Delta-Diona Delta-F Delta-Phoricol Delta1-dehydro-hydrocortisone Deltacortril Deltahydrocortisone Deltasolone Deltidrosol Dhasolone Di-Adreson-F Dontisolon D Estilsona Fisopred Frisolona Gupisone Hostacortin H Hydeltra Hydeltrasol Klismacort Kuhlprednon Lenisolone Lepi-Cortinolo Linola-H N Linola-H-Fett N Longiprednil Metacortandralone Meti Derm Meticortelone Opredsone Panafcortelone Precortisyl Pred-Clysma Predeltilone Predni-Coelin Predni-Helvacort Prednicortelone Prednisolonum Prelone Prenilone Sterane ; Drug: Thioguanine; Given PO, NG; Other Names: 2-Amino 6MP 2-Amino-1,7-dihydro-6H-purine-6-thione 2-Amino-6-mercaptopurine 2-Amino-6-purinethiol 2-Aminopurin-6-thiol 2-Aminopurine-6(1H)-thione 2-Aminopurine-6-thiol 2-Aminopurine-6-thiol Hemihydrate 2-Mercapto-6-aminopurine 6-Amino-2-mercaptopurine 6-Mercapto-2-aminopurine 6-Mercaptoguanine 6-TG 6H-Purine-6-thione, 2-amino-1,7-dihydro- (9CI) BW 5071 Lanvis Tabloid Thioguanine Hemihydrate Thioguanine Hydrate Tioguanin Tioguanine Wellcome U3B WR-1141 X 27 ; Drug: Vincristine; Given IV; Other Names: Leurocristine VCR Vincrystine ; Drug: Vincristine Sulfate; Given IV; Other Names: Kyocristine Leurocristine Sulfate Leurocristine, sulfate Oncovin Vincasar Vincosid Vincrex Vincristine, sulfate

Outcome Measures

Primary Outcome Measures

1. 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) [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 Outcome Measures

1. Biologic Activity, Defined as Global Deoxyribonucleic Acid (DNA) Methylation Change in Peripheral Blood Mononuclear Cells (PBMC)s [Four months]

   Will calculate the percentage of CpG site methylation for all patients before and after the first 2 courses of azacitidine. Means and standard deviations will be reported.

Other Outcome Measures

1. Event-free Survival (EFS) [Five years]

   Five year EFS estimation will be calculated from time of enrollment. Standard errors and confidence intervals for EFS will be calculated using Peto's method.

2. Minimal Residual Disease (MRD) [Five years]

   Descriptive analysis will be conducted to correlate MRD with the EFS for the KMT2A-R patients.

3. Pharmacokinetic (PK) Parameters of Azacitidine [Two months]

   Pharmacokinetic (PK) testing and analysis of azacitidine in infants will be performed by Covance.

4. Expansion of Infant T Lymphocytes by Stimulation With Artificial Antigen Presenting Cells [Three months]

   Optional biological study participation will explore the feasibility of T-cell collection for the purposes of chimeric antigen receptor (CAR) T-cell production from the peripheral blood in infants with ALL.

5. PD Data for Asparaginase Activity Following Pegaspargase Administration [Six months]

   Pharmacodynamic (PD) data for asparaginase activity following pegaspargase administration in infants will be collected, described, and correlated with EFS for the KMT2A-R patients.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A to 364 Days
• Sexes Eligible for Study: 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Children's Hospital of Alabama	Birmingham	Alabama	United States	35233
2	USA Health Strada Patient Care Center	Mobile	Alabama	United States	36604
3	Providence Alaska Medical Center	Anchorage	Alaska	United States	99508
4	Banner Children's at Desert	Mesa	Arizona	United States	85202
5	Phoenix Childrens Hospital	Phoenix	Arizona	United States	85016
6	Arkansas Children's Hospital	Little Rock	Arkansas	United States	72202-3591
7	Kaiser Permanente Downey Medical Center	Downey	California	United States	90242
8	Loma Linda University Medical Center	Loma Linda	California	United States	92354
9	Children's Hospital Los Angeles	Los Angeles	California	United States	90027
10	Cedars Sinai Medical Center	Los Angeles	California	United States	90048
11	Valley Children's Hospital	Madera	California	United States	93636
12	UCSF Benioff Children's Hospital Oakland	Oakland	California	United States	94609
13	Kaiser Permanente-Oakland	Oakland	California	United States	94611
14	Children's Hospital of Orange County	Orange	California	United States	92868
15	Lucile Packard Children's Hospital Stanford University	Palo Alto	California	United States	94304
16	University of California Davis Comprehensive Cancer Center	Sacramento	California	United States	95817
17	UCSF Medical Center-Mission Bay	San Francisco	California	United States	94158
18	Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center	Torrance	California	United States	90502
19	Children's Hospital Colorado	Aurora	Colorado	United States	80045
20	Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center	Denver	Colorado	United States	80218
21	Connecticut Children's Medical Center	Hartford	Connecticut	United States	06106
22	Yale University	New Haven	Connecticut	United States	06520
23	Alfred I duPont Hospital for Children	Wilmington	Delaware	United States	19803
24	Children's National Medical Center	Washington	District of Columbia	United States	20010
25	Golisano Children's Hospital of Southwest Florida	Fort Myers	Florida	United States	33908
26	University of Florida Health Science Center - Gainesville	Gainesville	Florida	United States	32610
27	Memorial Regional Hospital/Joe DiMaggio Children's Hospital	Hollywood	Florida	United States	33021
28	Nemours Children's Clinic-Jacksonville	Jacksonville	Florida	United States	32207
29	University of Miami Miller School of Medicine-Sylvester Cancer Center	Miami	Florida	United States	33136
30	Nicklaus Children's Hospital	Miami	Florida	United States	33155
31	AdventHealth Orlando	Orlando	Florida	United States	32803
32	Arnold Palmer Hospital for Children	Orlando	Florida	United States	32806
33	Nemours Children's Hospital	Orlando	Florida	United States	32827
34	Nemours Children's Clinic - Pensacola	Pensacola	Florida	United States	32504
35	Johns Hopkins All Children's Hospital	Saint Petersburg	Florida	United States	33701
36	Saint Joseph's Hospital/Children's Hospital-Tampa	Tampa	Florida	United States	33607
37	Saint Mary's Hospital	West Palm Beach	Florida	United States	33407
38	Children's Healthcare of Atlanta - Egleston	Atlanta	Georgia	United States	30322
39	Memorial Health University Medical Center	Savannah	Georgia	United States	31404
40	Kapiolani Medical Center for Women and Children	Honolulu	Hawaii	United States	96826
41	Saint Luke's Cancer Institute - Boise	Boise	Idaho	United States	83712
42	Lurie Children's Hospital-Chicago	Chicago	Illinois	United States	60611
43	University of Illinois	Chicago	Illinois	United States	60612
44	University of Chicago Comprehensive Cancer Center	Chicago	Illinois	United States	60637
45	Loyola University Medical Center	Maywood	Illinois	United States	60153
46	Advocate Children's Hospital-Oak Lawn	Oak Lawn	Illinois	United States	60453
47	Advocate Children's Hospital-Park Ridge	Park Ridge	Illinois	United States	60068
48	Saint Jude Midwest Affiliate	Peoria	Illinois	United States	61637
49	Southern Illinois University School of Medicine	Springfield	Illinois	United States	62702
50	Riley Hospital for Children	Indianapolis	Indiana	United States	46202
51	Saint Vincent Hospital and Health Care Center	Indianapolis	Indiana	United States	46260
52	Blank Children's Hospital	Des Moines	Iowa	United States	50309
53	University of Iowa/Holden Comprehensive Cancer Center	Iowa City	Iowa	United States	52242
54	University of Kentucky/Markey Cancer Center	Lexington	Kentucky	United States	40536
55	Norton Children's Hospital	Louisville	Kentucky	United States	40202
56	Children's Hospital New Orleans	New Orleans	Louisiana	United States	70118
57	Ochsner Medical Center Jefferson	New Orleans	Louisiana	United States	70121
58	Eastern Maine Medical Center	Bangor	Maine	United States	04401
59	Maine Children's Cancer Program	Scarborough	Maine	United States	04074
60	Sinai Hospital of Baltimore	Baltimore	Maryland	United States	21215
61	Johns Hopkins University/Sidney Kimmel Cancer Center	Baltimore	Maryland	United States	21287
62	Walter Reed National Military Medical Center	Bethesda	Maryland	United States	20889-5600
63	Tufts Children's Hospital	Boston	Massachusetts	United States	02111
64	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02215
65	UMass Memorial Medical Center - University Campus	Worcester	Massachusetts	United States	01655
66	C S Mott Children's Hospital	Ann Arbor	Michigan	United States	48109
67	Ascension Saint John Hospital	Detroit	Michigan	United States	48236
68	Michigan State University Clinical Center	East Lansing	Michigan	United States	48824-7016
69	Helen DeVos Children's Hospital at Spectrum Health	Grand Rapids	Michigan	United States	49503
70	Bronson Methodist Hospital	Kalamazoo	Michigan	United States	49007
71	Beaumont Children's Hospital-Royal Oak	Royal Oak	Michigan	United States	48073
72	University of Minnesota/Masonic Cancer Center	Minneapolis	Minnesota	United States	55455
73	Mayo Clinic in Rochester	Rochester	Minnesota	United States	55905
74	University of Mississippi Medical Center	Jackson	Mississippi	United States	39216
75	Columbia Regional	Columbia	Missouri	United States	65201
76	Children's Mercy Hospitals and Clinics	Kansas City	Missouri	United States	64108
77	Cardinal Glennon Children's Medical Center	Saint Louis	Missouri	United States	63104
78	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
79	Mercy Hospital Saint Louis	Saint Louis	Missouri	United States	63141
80	Children's Hospital and Medical Center of Omaha	Omaha	Nebraska	United States	68114
81	University of Nebraska Medical Center	Omaha	Nebraska	United States	68198
82	University Medical Center of Southern Nevada	Las Vegas	Nevada	United States	89102
83	Sunrise Hospital and Medical Center	Las Vegas	Nevada	United States	89109
84	Alliance for Childhood Diseases/Cure 4 the Kids Foundation	Las Vegas	Nevada	United States	89135
85	Summerlin Hospital Medical Center	Las Vegas	Nevada	United States	89144
86	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire	United States	03756
87	Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
88	Morristown Medical Center	Morristown	New Jersey	United States	07960
89	Saint Peter's University Hospital	New Brunswick	New Jersey	United States	08901
90	Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital	New Brunswick	New Jersey	United States	08903
91	Newark Beth Israel Medical Center	Newark	New Jersey	United States	07112
92	Saint Joseph's Regional Medical Center	Paterson	New Jersey	United States	07503
93	Albany Medical Center	Albany	New York	United States	12208
94	Montefiore Medical Center - Moses Campus	Bronx	New York	United States	10467
95	Roswell Park Cancer Institute	Buffalo	New York	United States	14263
96	NYU Winthrop Hospital	Mineola	New York	United States	11501
97	The Steven and Alexandra Cohen Children's Medical Center of New York	New Hyde Park	New York	United States	11040
98	Laura and Isaac Perlmutter Cancer Center at NYU Langone	New York	New York	United States	10016
99	Mount Sinai Hospital	New York	New York	United States	10029
100	NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center	New York	New York	United States	10032
101	University of Rochester	Rochester	New York	United States	14642
102	Stony Brook University Medical Center	Stony Brook	New York	United States	11794
103	State University of New York Upstate Medical University	Syracuse	New York	United States	13210
104	New York Medical College	Valhalla	New York	United States	10595
105	Mission Hospital	Asheville	North Carolina	United States	28801
106	UNC Lineberger Comprehensive Cancer Center	Chapel Hill	North Carolina	United States	27599
107	Carolinas Medical Center/Levine Cancer Institute	Charlotte	North Carolina	United States	28203
108	Duke University Medical Center	Durham	North Carolina	United States	27710
109	East Carolina University	Greenville	North Carolina	United States	27834
110	Wake Forest University Health Sciences	Winston-Salem	North Carolina	United States	27157
111	Sanford Broadway Medical Center	Fargo	North Dakota	United States	58122
112	Children's Hospital Medical Center of Akron	Akron	Ohio	United States	44308
113	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio	United States	45229
114	Cleveland Clinic Foundation	Cleveland	Ohio	United States	44195
115	Nationwide Children's Hospital	Columbus	Ohio	United States	43205
116	Dayton Children's Hospital	Dayton	Ohio	United States	45404
117	ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital	Toledo	Ohio	United States	43606
118	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma	United States	73104
119	Legacy Emanuel Children's Hospital	Portland	Oregon	United States	97227
120	Lehigh Valley Hospital-Cedar Crest	Allentown	Pennsylvania	United States	18103
121	Lehigh Valley Hospital - Muhlenberg	Bethlehem	Pennsylvania	United States	18017
122	Geisinger Medical Center	Danville	Pennsylvania	United States	17822
123	Penn State Children's Hospital	Hershey	Pennsylvania	United States	17033
124	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania	United States	19104
125	Saint Christopher's Hospital for Children	Philadelphia	Pennsylvania	United States	19134
126	Children's Hospital of Pittsburgh of UPMC	Pittsburgh	Pennsylvania	United States	15224
127	Rhode Island Hospital	Providence	Rhode Island	United States	02903
128	Prisma Health Richland Hospital	Columbia	South Carolina	United States	29203
129	BI-LO Charities Children's Cancer Center	Greenville	South Carolina	United States	29605
130	Sanford USD Medical Center - Sioux Falls	Sioux Falls	South Dakota	United States	57117-5134
131	T C Thompson Children's Hospital	Chattanooga	Tennessee	United States	37403
132	East Tennessee Childrens Hospital	Knoxville	Tennessee	United States	37916
133	The Children's Hospital at TriStar Centennial	Nashville	Tennessee	United States	37203
134	Vanderbilt University/Ingram Cancer Center	Nashville	Tennessee	United States	37232
135	Dell Children's Medical Center of Central Texas	Austin	Texas	United States	78723
136	Driscoll Children's Hospital	Corpus Christi	Texas	United States	78411
137	Medical City Dallas Hospital	Dallas	Texas	United States	75230
138	UT Southwestern/Simmons Cancer Center-Dallas	Dallas	Texas	United States	75390
139	El Paso Children's Hospital	El Paso	Texas	United States	79905
140	Cook Children's Medical Center	Fort Worth	Texas	United States	76104
141	Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center	Houston	Texas	United States	77030
142	Covenant Children's Hospital	Lubbock	Texas	United States	79410
143	UMC Cancer Center / UMC Health System	Lubbock	Texas	United States	79415
144	Children's Hospital of San Antonio	San Antonio	Texas	United States	78207
145	Methodist Children's Hospital of South Texas	San Antonio	Texas	United States	78229
146	University of Texas Health Science Center at San Antonio	San Antonio	Texas	United States	78229
147	Scott and White Memorial Hospital	Temple	Texas	United States	76508
148	Primary Children's Hospital	Salt Lake City	Utah	United States	84113
149	University of Vermont and State Agricultural College	Burlington	Vermont	United States	05405
150	University of Virginia Cancer Center	Charlottesville	Virginia	United States	22908
151	Inova Fairfax Hospital	Falls Church	Virginia	United States	22042
152	Children's Hospital of The King's Daughters	Norfolk	Virginia	United States	23507
153	Carilion Children's	Roanoke	Virginia	United States	24014
154	Seattle Children's Hospital	Seattle	Washington	United States	98105
155	Providence Sacred Heart Medical Center and Children's Hospital	Spokane	Washington	United States	99204
156	West Virginia University Charleston Division	Charleston	West Virginia	United States	25304
157	West Virginia University Healthcare	Morgantown	West Virginia	United States	26506
158	Saint Vincent Hospital Cancer Center Green Bay	Green Bay	Wisconsin	United States	54301
159	University of Wisconsin Hospital and Clinics	Madison	Wisconsin	United States	53792
160	Marshfield Medical Center-Marshfield	Marshfield	Wisconsin	United States	54449
161	Children's Hospital of Wisconsin	Milwaukee	Wisconsin	United States	53226
162	Princess Margaret Hospital for Children	Perth	Western Australia	Australia	6008
163	Perth Children's Hospital	Perth	Western Australia	Australia	6009
164	CancerCare Manitoba	Winnipeg	Manitoba	Canada	R3E 0V9
165	Janeway Child Health Centre	Saint John's	Newfoundland and Labrador	Canada	A1B 3V6
166	IWK Health Centre	Halifax	Nova Scotia	Canada	B3K 6R8
167	Kingston Health Sciences Centre	Kingston	Ontario	Canada	K7L 2V7
168	Children's Hospital	London	Ontario	Canada	N6A 5W9
169	Children's Hospital of Eastern Ontario	Ottawa	Ontario	Canada	K1H 8L1
170	Hospital for Sick Children	Toronto	Ontario	Canada	M5G 1X8
171	The Montreal Children's Hospital of the MUHC	Montreal	Quebec	Canada	H3H 1P3
172	HIMA San Pablo Oncologic Hospital	Caguas		Puerto Rico	00726
173	San Jorge Children's Hospital	San Juan		Puerto Rico	00912
174	University Pediatric Hospital	San Juan		Puerto Rico	00926

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Erin M Guest, Children's Oncology Group

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Sep 25, 2019

More Information

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT02828358
• Other Study ID Numbers: NCI-2016-00973; NCI-2016-00973; s17-00488; AALL15P1; AALL15P1; U10CA180886
• First Posted: Jul 11, 2016
• Last Update Posted: Nov 18, 2021
• Last Verified: Nov 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Acute Disease; Calcium, Dietary; Leucovorin; Folic Acid; Cytarabine; Dexamethasone; Dexamethasone acetate; Prednisolone; Methylprednisolone Acetate; Methylprednisolone; Methylprednisolone Hemisuccinate; Prednisolone acetate; Hydrocortisone; Hydrocortisone 17-butyrate 21-propionate; Hydrocortisone acetate; Hydrocortisone hemisuccinate; Cortisone; Cyclophosphamide; Methotrexate; Vincristine; Azacitidine; Daunorubicin; Asparaginase; Mercaptopurine; Pegaspargase; Thioguanine; Prednisolone hemisuccinate; Prednisolone phosphate; BB 1101; Calcium; 2-Aminopurine; Levoleucovorin

Study Results

Participant Flow

Recruitment Details	Infants less than 1 year of age with newly diagnosed B lymphoblastic leukemia (also termed B-precursor acute lymphoblastic leukemia) or acute leukemia of ambiguous lineage
Pre-assignment Detail	Enrolled patients receive common induction therapy. Genetic evaluation results in patients being stratified into KMT2A-Germline and KMT2A-Rearranged groups. KMT2A-Germline patients go off protocol therapy post-induction.

Arm/Group Title	KMT2A-Rearranged	KMT2A-Germline
Arm/Group Description	INDUCTION: Same as KMT2A-Germline (Group 2). AZACITIDINE (AZA) I: AZA over 10-40 minutes for 5 days. CONSOLIDATION: cyclophosphamide days 1/29; mercaptopurine (6-MP) days 1-28; ARA-C days 3-6, 10-13, 17-20, 24-27; MTX IT day 24; HC days 10/24. AZA II: Same as AZA I. INTERIM MAINTENANCE: 6-MP days 1-14; MTX 1/2/8/9; leucovorin calcium days 3-4,10-11; HC days 2/9; ARA-C days 15-16, 22-23; PEG day 23. AZA III: Same as AZA I. DELAYED INTENSIFICATION (DI) I: PEG day 1; dexamethasone days 1-14, 15-21; thioguanine days 1-28; vincristine sulfate and daunorubicin hydrochloride days 1/8/15/22; ARA-C days 1-5, 9-12, 15-19, 23-26; HC on days 1/15. AZA IV: Same as AZA I. DI II: thioguanine days 1-14; cyclophosphamide days 1/15; ARA-C days 2-5, 9-12. MAINTENANCE: 6-MP days 1-168, MTX IT day 1/92; MTX weekly days 8-91,98-168; HC day 1/57/99; ARA-C day 57. Starting day 169, 6-MP days 1-84 and MTX weekly. Cycles repeat every 84 days for 2 years from start of Induction.	Induction: 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 (ARA-C) IV over 30 minutes on days 8-21 and IT on day 15, dexamethasone PO, NG, or IV TID on days 8-28, vincristine sulfate IV over 1 minute on days 8, 15, 22, and 29, pegaspargase (PEG) IV over 1-2 hours or intramuscularly (IM) on day 12, and hydrocortisone sodium succinate (HC) IT on days 15 and 29 in the absence of disease progression or unacceptable toxicity.
Period Title: Overall Study
STARTED	56	22
COMPLETED	11	0
NOT COMPLETED	45	22

Baseline Characteristics

Arm/Group Title	KMT2A-Rearranged	KMT2A-Germline	Total
Arm/Group Description	INDUCTION: Same as KMT2A-Germline (Group 2). AZACITIDINE (AZA) I: AZA over 10-40 minutes for 5 days. CONSOLIDATION: cyclophosphamide days 1/29; mercaptopurine (6-MP) days 1-28; ARA-C days 3-6, 10-13, 17-20, 24-27; MTX IT day 24; HC days 10/24. AZA II: Same as AZA I. INTERIM MAINTENANCE: 6-MP days 1-14; MTX 1/2/8/9; leucovorin calcium days 3-4,10-11; HC days 2/9; ARA-C days 15-16, 22-23; PEG day 23. AZA III: Same as AZA I. DELAYED INTENSIFICATION (DI) I: PEG day 1; dexamethasone days 1-14, 15-21; thioguanine days 1-28; vincristine sulfate and daunorubicin hydrochloride days 1/8/15/22; ARA-C days 1-5, 9-12, 15-19, 23-26; HC on days 1/15. AZA IV: Same as AZA I. DI II: thioguanine days 1-14; cyclophosphamide days 1/15; ARA-C days 2-5, 9-12. MAINTENANCE: 6-MP days 1-168, MTX IT day 1/92; MTX weekly days 8-91,98-168; HC day 1/57/99; ARA-C day 57. Starting day 169, 6-MP days 1-84 and MTX weekly. Cycles repeat every 84 days for 2 years from start of Induction.	Induction: 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 (ARA-C) IV over 30 minutes on days 8-21 and IT on day 15, dexamethasone PO, NG, or IV TID on days 8-28, vincristine sulfate IV over 1 minute on days 8, 15, 22, and 29, pegaspargase (PEG) IV over 1-2 hours or intramuscularly (IM) on day 12, and hydrocortisone sodium succinate (HC) IT on days 15 and 29 in the absence of disease progression or unacceptable toxicity.	Total of all reporting groups
Overall Participants	56	22	78
Age (Count of Participants)
<=18 years	56 100%	22 100%	78 100%
Between 18 and 65 years	0 0%	0 0%	0 0%
>=65 years	0 0%	0 0%	0 0%
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	0.48 (0.29)	0.74 (0.2)	0.55 (0.29)
Sex: Female, Male (Count of Participants)
Female	35 62.5%	12 54.5%	47 60.3%
Male	21 37.5%	10 45.5%	31 39.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	11 19.6%	4 18.2%	15 19.2%
Not Hispanic or Latino	40 71.4%	17 77.3%	57 73.1%
Unknown or Not Reported	5 8.9%	1 4.5%	6 7.7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	1 4.5%	1 1.3%
Asian	4 7.1%	1 4.5%	5 6.4%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	3 5.4%	2 9.1%	5 6.4%
White	40 71.4%	15 68.2%	55 70.5%
More than one race	0 0%	1 4.5%	1 1.3%
Unknown or Not Reported	9 16.1%	2 9.1%	11 14.1%

Outcome Measures

1. Primary Outcome

Title	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)
Description	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.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

KMT2A-Rearranged patients evaluable for dose-limiting toxicity assessment

Arm/Group Title	KMT2A-Rearranged
Arm/Group Description	INDUCTION: Same as KMT2A-Germline (Group 2). AZACITIDINE (AZA) I: AZA over 10-40 minutes for 5 days. CONSOLIDATION: cyclophosphamide days 1/29; mercaptopurine (6-MP) days 1-28; ARA-C days 3-6, 10-13, 17-20, 24-27; MTX IT day 24; HC days 10/24. AZA II: Same as AZA I. INTERIM MAINTENANCE: 6-MP days 1-14; MTX 1/2/8/9; leucovorin calcium days 3-4,10-11; HC days 2/9; ARA-C days 15-16, 22-23; PEG day 23. AZA III: Same as AZA I. DELAYED INTENSIFICATION (DI) I: PEG day 1; dexamethasone days 1-14, 15-21; thioguanine days 1-28; vincristine sulfate and daunorubicin hydrochloride days 1/8/15/22; ARA-C days 1-5, 9-12, 15-19, 23-26; HC on days 1/15. AZA IV: Same as AZA I. DI II: thioguanine days 1-14; cyclophosphamide days 1/15; ARA-C days 2-5, 9-12. MAINTENANCE: 6-MP days 1-168, MTX IT day 1/92; MTX weekly days 8-91,98-168; HC day 1/57/99; ARA-C day 57. Starting day 169, 6-MP days 1-84 and MTX weekly. Cycles repeat every 84 days for 2 years from start of Induction.
Measure Participants	31
Number (95% Confidence Interval) [percentage of participants]	6.45 11.5%

2. Secondary Outcome

Title	Biologic Activity, Defined as Global Deoxyribonucleic Acid (DNA) Methylation Change in Peripheral Blood Mononuclear Cells (PBMC)s
Description	Will calculate the percentage of CpG site methylation for all patients before and after the first 2 courses of azacitidine. Means and standard deviations will be reported.
Time Frame	Four months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

3. Other Pre-specified Outcome

Title	Event-free Survival (EFS)
Description	Five year EFS estimation will be calculated from time of enrollment. Standard errors and confidence intervals for EFS will be calculated using Peto's method.
Time Frame	Five years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

4. Other Pre-specified Outcome

Title	Minimal Residual Disease (MRD)
Description	Descriptive analysis will be conducted to correlate MRD with the EFS for the KMT2A-R patients.
Time Frame	Five years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

5. Other Pre-specified Outcome

Title	Pharmacokinetic (PK) Parameters of Azacitidine
Description	Pharmacokinetic (PK) testing and analysis of azacitidine in infants will be performed by Covance.
Time Frame	Two months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

6. Other Pre-specified Outcome

Title	Expansion of Infant T Lymphocytes by Stimulation With Artificial Antigen Presenting Cells
Description	Optional biological study participation will explore the feasibility of T-cell collection for the purposes of chimeric antigen receptor (CAR) T-cell production from the peripheral blood in infants with ALL.
Time Frame	Three months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

7. Other Pre-specified Outcome

Title	PD Data for Asparaginase Activity Following Pegaspargase Administration
Description	Pharmacodynamic (PD) data for asparaginase activity following pegaspargase administration in infants will be collected, described, and correlated with EFS for the KMT2A-R patients.
Time Frame	Six months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	Up to 5 years
Adverse Event Reporting Description	Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution via expedited reporting (NCI AdEERs / CAeRs). All remaining CTCAEs collected by means other than expedited reporting are non-serious and are reported in the "AE Other" table. Ineligible patients are excluded from reporting of adverse events. All-Cause Mortality includes all deaths collected on the study.
Arm/Group Title	KMT2A-Rearranged		KMT2A-Germline
Arm/Group Description	INDUCTION: Same as KMT2A-Germline (Group 2). AZACITIDINE (AZA) I: AZA over 10-40 minutes for 5 days. CONSOLIDATION: cyclophosphamide days 1/29; mercaptopurine (6-MP) days 1-28; ARA-C days 3-6, 10-13, 17-20, 24-27; MTX IT day 24; HC days 10/24. AZA II: Same as AZA I. INTERIM MAINTENANCE: 6-MP days 1-14; MTX 1/2/8/9; leucovorin calcium days 3-4,10-11; HC days 2/9; ARA-C days 15-16, 22-23; PEG day 23. AZA III: Same as AZA I. DELAYED INTENSIFICATION (DI) I: PEG day 1; dexamethasone days 1-14, 15-21; thioguanine days 1-28; vincristine sulfate and daunorubicin hydrochloride days 1/8/15/22; ARA-C days 1-5, 9-12, 15-19, 23-26; HC on days 1/15. AZA IV: Same as AZA I. DI II: thioguanine days 1-14; cyclophosphamide days 1/15; ARA-C days 2-5, 9-12. MAINTENANCE: 6-MP days 1-168, MTX IT day 1/92; MTX weekly days 8-91,98-168; HC day 1/57/99; ARA-C day 57. Starting day 169, 6-MP days 1-84 and MTX weekly. Cycles repeat every 84 days for 2 years from start of Induction.		Induction: 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 (ARA-C) IV over 30 minutes on days 8-21 and IT on day 15, dexamethasone PO, NG, or IV TID on days 8-28, vincristine sulfate IV over 1 minute on days 8, 15, 22, and 29, pegaspargase (PEG) IV over 1-2 hours or intramuscularly (IM) on day 12, and hydrocortisone sodium succinate (HC) IT on days 15 and 29 in the absence of disease progression or unacceptable toxicity.
All Cause Mortality
	KMT2A-Rearranged		KMT2A-Germline
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	17/56 (30.4%)		1/22 (4.5%)
Serious Adverse Events
	KMT2A-Rearranged		KMT2A-Germline
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	34/56 (60.7%)		1/22 (4.5%)
Blood and lymphatic system disorders
Blood and lymphatic system disorders - Other, specify	1/56 (1.8%)	1	0/22 (0%)	0
Disseminated intravascular coagulation	1/56 (1.8%)	1	0/22 (0%)	0
Leukocytosis	1/56 (1.8%)	1	0/22 (0%)	0
Cardiac disorders
Cardiac arrest	1/56 (1.8%)	1	0/22 (0%)	0
Gastrointestinal disorders
Enterocolitis	1/56 (1.8%)	1	0/22 (0%)	0
Mucositis oral	5/56 (8.9%)	5	0/22 (0%)	0
Pancreatitis	1/56 (1.8%)	1	0/22 (0%)	0
Typhlitis	1/56 (1.8%)	1	0/22 (0%)	0
Rectal mucositis	1/56 (1.8%)	1	0/22 (0%)	0
General disorders
Death NOS	11/56 (19.6%)	11	1/22 (4.5%)	1
General disorders and administration site conditions - Other, specify	2/56 (3.6%)	2	0/22 (0%)	0
Multi-organ failure	1/56 (1.8%)	1	0/22 (0%)	0
Hepatobiliary disorders
Hepatic failure	1/56 (1.8%)	1	0/22 (0%)	0
Infections and infestations
Sepsis	1/56 (1.8%)	1	0/22 (0%)	0
Enterocolitis infectious	1/56 (1.8%)	1	0/22 (0%)	0
Investigations
Alanine aminotransferase increased	1/56 (1.8%)	1	0/22 (0%)	0
Aspartate aminotransferase increased	1/56 (1.8%)	1	0/22 (0%)	0
Lipase increased	1/56 (1.8%)	1	0/22 (0%)	0
Neutrophil count decreased	2/56 (3.6%)	2	0/22 (0%)	0
Urine output decreased	1/56 (1.8%)	1	0/22 (0%)	0
Metabolism and nutrition disorders
Hyperglycemia	1/56 (1.8%)	1	0/22 (0%)	0
Hypertriglyceridemia	2/56 (3.6%)	2	0/22 (0%)	0
Hypokalemia	3/56 (5.4%)	3	0/22 (0%)	0
Musculoskeletal and connective tissue disorders
Muscle weakness lower limb	1/56 (1.8%)	1	0/22 (0%)	0
Nervous system disorders
Seizure	1/56 (1.8%)	1	0/22 (0%)	0
Renal and urinary disorders
Acute kidney injury	1/56 (1.8%)	1	0/22 (0%)	0
Respiratory, thoracic and mediastinal disorders
Pleural effusion	2/56 (3.6%)	2	0/22 (0%)	0
Skin and subcutaneous tissue disorders
Skin ulceration	3/56 (5.4%)	3	0/22 (0%)	0
Vascular disorders
Hematoma	1/56 (1.8%)	1	0/22 (0%)	0
Other (Not Including Serious) Adverse Events
	KMT2A-Rearranged		KMT2A-Germline
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	36/56 (64.3%)		10/22 (45.5%)
Blood and lymphatic system disorders
Febrile neutropenia	3/56 (5.4%)	4	1/22 (4.5%)	1
Gastrointestinal disorders
Gastrointestinal disorders - Other, specify	1/56 (1.8%)	1	0/22 (0%)	0
Mucositis oral	10/56 (17.9%)	10	2/22 (9.1%)	2
Anal mucositis	2/56 (3.6%)	2	1/22 (4.5%)	1
Infections and infestations
Catheter related infection	4/56 (7.1%)	4	0/22 (0%)	0
Infections and infestations - Other, specify	17/56 (30.4%)	37	4/22 (18.2%)	4
Sepsis	6/56 (10.7%)	6	1/22 (4.5%)	1
Sinusitis	1/56 (1.8%)	1	0/22 (0%)	0
Skin infection	6/56 (10.7%)	8	0/22 (0%)	0
Upper respiratory infection	4/56 (7.1%)	5	0/22 (0%)	0
Urinary tract infection	2/56 (3.6%)	2	0/22 (0%)	0
Wound infection	1/56 (1.8%)	1	1/22 (4.5%)	1
Bronchial infection	1/56 (1.8%)	1	0/22 (0%)	0
Enterocolitis infectious	3/56 (5.4%)	4	0/22 (0%)	0
Lung infection	2/56 (3.6%)	2	0/22 (0%)	0
Soft tissue infection	1/56 (1.8%)	1	0/22 (0%)	0
Small intestine infection	1/56 (1.8%)	2	0/22 (0%)	0
Investigations
Alanine aminotransferase increased	4/56 (7.1%)	6	0/22 (0%)	0
Blood bilirubin increased	3/56 (5.4%)	3	1/22 (4.5%)	1
Creatinine increased	1/56 (1.8%)	1	0/22 (0%)	0
Neutrophil count decreased	2/56 (3.6%)	2	2/22 (9.1%)	2
GGT increased	1/56 (1.8%)	1	0/22 (0%)	0
Metabolism and nutrition disorders
Anorexia	1/56 (1.8%)	1	0/22 (0%)	0
Hyperglycemia	2/56 (3.6%)	3	0/22 (0%)	0
Hyperkalemia	1/56 (1.8%)	1	0/22 (0%)	0
Hypertriglyceridemia	4/56 (7.1%)	4	0/22 (0%)	0
Hypoalbuminemia	1/56 (1.8%)	1	0/22 (0%)	0
Hypocalcemia	3/56 (5.4%)	3	0/22 (0%)	0
Hypokalemia	1/56 (1.8%)	1	2/22 (9.1%)	2
Tumor lysis syndrome	1/56 (1.8%)	1	0/22 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify	0/56 (0%)	0	1/22 (4.5%)	1
Renal and urinary disorders
Acute kidney injury	1/56 (1.8%)	1	0/22 (0%)	0
Respiratory, thoracic and mediastinal disorders
Apnea	0/56 (0%)	0	1/22 (4.5%)	1
Respiratory failure	1/56 (1.8%)	1	1/22 (4.5%)	1
Skin and subcutaneous tissue disorders
Skin and subcutaneous tissue disorders - Other, specify	1/56 (1.8%)	1	0/22 (0%)	0
Skin ulceration	2/56 (3.6%)	2	0/22 (0%)	0
Vascular disorders
Vascular disorders - Other, specify	1/56 (1.8%)	1	0/22 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.