Combination Chemotherapy and Inotuzumab Ozogamicin in Treating Patients With B Acute Lymphoblastic Leukemia

• Sponsor: M.D. Anderson Cancer Center (Other)
• Overall Status: Terminated
• CT.gov ID: NCT03488225
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 4
• Location: 1
• Arm: 1
• Actual Duration (Months): 24.2
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This phase II trial studies how well combination chemotherapy and inotuzumab ozogamicin work in treating patients with B acute lymphoblastic leukemia. Drugs used in chemotherapy, such as cyclophosphamide, vincristine sulfate, doxorubicin hydrochloride, dexamethasone, methotrexate and cytarabine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Immunotherapy with monoclonal antibodies, such as inotuzumab ozogamicin, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving combination chemotherapy and inotuzumab ozogamicin may work better at treating B acute lymphoblastic leukemia.

Condition or Disease	Intervention/Treatment	Phase
Acute Lymphoblastic Leukemia in Remission; B Acute Lymphoblastic Leukemia; B Acute Lymphoblastic Leukemia, Philadelphia Chromosome Negative	Drug: Cyclophosphamide; Drug: Cytarabine; Drug: Dexamethasone; Drug: Doxorubicin Hydrochloride; Biological: Inotuzumab Ozogamicin; Other: Laboratory Biomarker Analysis; Drug: Leucovorin Calcium; Drug: Mercaptopurine; Drug: Methotrexate; Biological: Ofatumumab; Drug: Prednisone; Biological: Rituximab; Drug: Vincristine Sulfate	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. To evaluate the clinical efficacy of the sequential combination of hyper-CVAD (hyperfractionated cyclophosphamide, vincristine sulfate, doxorubicin hydrochloride, dexamethasone, methotrexate and cytarabine) + inotuzumab ozogamicin in patients with newly diagnosed B-cell acute lymphocytic leukemia (ALL) in terms of event-free survival (EFS).

SECONDARY OBJECTIVES:

1. To evaluate other efficacy endpoints such as overall survival, overall response rate, minimal residual disease (MRD) negativity rate as well as the safety of this combination.

OUTLINE:

INTENSIVE CHEMOTHERAPY: Patients receive cyclophosphamide intravenously (IV) over 3 hours every 12 hours on days 1-3 and dexamethasone IV or orally (PO) on days 1-4 and 11-14 of courses 1 and 3. Patients may receive ofatumumab IV over 2 hours on days 1, 2 and 11 of course 1, days 1 and 8 of courses 2 and 4, and days 1 and 11 of course 3, or rituximab IV over 2 hours on days 1 and 11 of courses 1 and 3, and days 1 and 8 of courses 2 and 4. Patients also receive methotrexate intrathecally (IT) on day 2 of courses 1 and 3, IV over 24 hours on day 1 and IT on day 8 of courses 2 and 4, doxorubicin hydrochloride IV over 24 hours on day 4 of courses 1 and 3, vincristine sulfate IV over 1 hour on days 4 and 11 of courses 1 and 3, cytarabine IT on day 7 of courses 1 and 3, and IV over 2 hours every 12 hours on days 2 and 3, and IT on day 5 of courses 2 and 4, leucovorin calcium IV 4 times a days on day 2 of courses 2 and 4. Patients then receive inotuzumab ozogamicin IV over 1 hour on days 1 and 8 of courses 5-8. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity.

MAINTENANCE THERAPY: Patients receive mercaptopurine PO thrice a day, methotrexate PO once a week, vincristine sulfate IV over 1 hour on day 1 and prednisone PO on days 1-5. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days and every 6 months.

Study Design

• Study Type: Interventional
• Actual Enrollment: 4 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Study of the Hyper-CVAD Regimen in Sequential Combination With Inotuzumab Ozogamicin as Frontline Therapy for Adults With B-Cell Lineage Acute Lymphocytic Leukemia
• Actual Study Start Date: Mar 28, 2018
• Actual Primary Completion Date: Apr 2, 2020
• Actual Study Completion Date: Apr 2, 2020

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Treatment (hyper-CVAD, inotuzumab ozogamicin) See detailed description.

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 Cyclophosphamidum Cyclophosphan Cyclophosphane Cyclophosphanum Cyclostin Cyclostine Cytophosphan Cytophosphane Cytoxan Fosfaseron Genoxal Genuxal Ledoxina Mitoxan Neosar Revimmune Syklofosfamid WR- 138719 ; Drug: Cytarabine; Given IT or IV; 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: Dexamethasone; Given IV or PO; Other Names: Aacidexam Adexone Aknichthol Dexa Alba-Dex Alin Alin Depot Alin Oftalmico Amplidermis Anemul mono Auricularum Auxiloson Baycuten Baycuten N Cortidexason Cortisumman Decacort Decadrol Decadron 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 Dexamethasonum Dexamonozon Dexapos Dexinoral Dexone Dinormon Fluorodelta Fortecortin Gammacorten Hexadecadrol Hexadrol Lokalison-F Loverine Methylfluorprednisolone Millicorten Mymethasone Orgadrone Spersadex Visumetazone ; Drug: Doxorubicin Hydrochloride; Given IV; Other Names: 5,12-Naphthacenedione, 10-[(3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy]-7,8, 9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-, hydrochloride, (8S-cis)- (9CI) ADM Adriacin Adriamycin Adriamycin Hydrochloride Adriamycin PFS Adriamycin RDF ADRIAMYCIN, HYDROCHLORIDE Adriamycine Adriblastina Adriblastine Adrimedac Chloridrato de Doxorrubicina DOX DOXO-CELL Doxolem Doxorubicin.HCl Doxorubin Farmiblastina FI 106 FI-106 hydroxydaunorubicin Rubex ; Biological: Inotuzumab Ozogamicin; Given IV; Other Names: Besponsa CMC-544 Way 207294 WAY-207294 ; Other: Laboratory Biomarker Analysis; Correlative studies; Drug: Leucovorin Calcium; Given 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; 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 or 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 ; Biological: Ofatumumab; Given IV; Other Names: Arzerra GSK1841157 HuMax-CD20 HuMax-CD20, 2F2 ; Drug: Prednisone; Given PO; Other Names: .delta.1-Cortisone 1, 2-Dehydrocortisone Adasone Cortancyl Dacortin DeCortin Decortisyl Decorton Delta 1-Cortisone Delta-Dome Deltacortene Deltacortisone Deltadehydrocortisone Deltasone Deltison Deltra Econosone Lisacort Meprosona-F Metacortandracin Meticorten Ofisolona Orasone Panafcort Panasol-S Paracort PRED Predicor Predicorten Prednicen-M Prednicort Prednidib Prednilonga Predniment Prednisonum Prednitone Promifen Servisone SK-Prednisone ; Biological: Rituximab; Given IV; Other Names: ABP 798 BI 695500 C2B8 Monoclonal Antibody Chimeric Anti-CD20 Antibody CT-P10 IDEC-102 IDEC-C2B8 IDEC-C2B8 Monoclonal Antibody MabThera Monoclonal Antibody IDEC-C2B8 PF-05280586 Rituxan Rituximab Biosimilar ABP 798 Rituximab Biosimilar BI 695500 Rituximab Biosimilar CT-P10 Rituximab Biosimilar GB241 Rituximab Biosimilar IBI301 Rituximab Biosimilar PF-05280586 Rituximab Biosimilar RTXM83 Rituximab Biosimilar SAIT101 RTXM83 ; Drug: Vincristine Sulfate; Given IV; Other Names: Kyocristine Leurocristine sulfate Leurocristine, sulfate Oncovin Vincasar Vincosid Vincrex Vincristine, sulfate

Outcome Measures

Primary Outcome Measures

1. Event-Free Survival [Start of treatment up to 2 years]

   Event-free survival defined as the time interval from date of treatment start until the date of death, disease progression or relapse.

Secondary Outcome Measures

1. Overall Survival [Start of treatment up to 2 years]

   Time from date of treatment start until date of death due to any cause or last Follow-up.

2. Participants to Achieve Complete Remission (CR): [Start of treatment up to 2 years]

   Complete Remission (CR) is defined as - Normalization of the peripheral blood and bone marrow blasts </= 5% in normocellular or hypercellular marrow, granulocyte count of 1x10^9/L or above and platelets >/= 100X10^9/L and complete resolution of all sites of extramedullary disease.

3. Number of Participants With Minimal Residual Disease (MRD) Negativity [Start of treatment up to 2 years]

   MRD levels continuously assessed during induction and consolidation therapy by 6-color multiparameter flow. MRD negativity defined by a value of at least 10-4 and confirmed on a second bone marrow aspiration/biopsy performed after a subsequent cycle.

4. Number of Participants With Adverse Events [Start of treatment up to 30 days after last dose received.]

   For the purpose of toxicity monitoring, toxicities are defined as any treatment -related grade 3 or 4 non-hematologic AEs occurred any time during the trial.NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 utilized for adverse event reporting.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 16 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients with newly diagnosed, previously untreated B-lineage ALL, or having achieved complete remission (CR) with one course of induction chemotherapy

• Patients with extramedullary disease only are eligible

• Failure to one induction course of chemotherapy (these patients will be analyzed separately)

• Performance status of 0-3

• Creatinine less than or equal to 2.0 mg/dL (unless considered tumor related)

• Bilirubin less than or equal to 2.0 mg/dL (unless considered tumor related)

• Adequate cardiac function as assessed by history and physical examination

• No active or co-existing malignancy with life expectancy less than 12 months

• Women of childbearing potential (WOCBP) or male subjects with a partner who is WOCBP must agree to use contraception during the study, if sexually active

Exclusion Criteria:

• Pregnant or nursing women

• Known to be human immunodeficiency virus (HIV)-positive

• Philadelphia chromosome (Ph)-positive ALL

• Active and uncontrolled disease/infection as judged by the treating physician

• Unable or unwilling to sign the consent form

• Subjects who have current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver involvement or stable chronic liver disease per investigator assessment)

• Chronic or current infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment such as, but not limited to, chronic renal infection, chronic chest infection with bronchiectasis, tuberculosis and active hepatitis C

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	M D Anderson Cancer Center	Houston	Texas	United States	77030

Sponsors and Collaborators

• M.D. Anderson Cancer Center
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Elias Jabbour, M.D. Anderson Cancer Center

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Aug 6, 2018

More Information

Additional Information:

• University of Texas MD Anderson Cancer Center Website

Publications

None provided.

• Responsible Party: M.D. Anderson Cancer Center
• ClinicalTrials.gov Identifier: NCT03488225
• Other Study ID Numbers: 2015-0922; NCI-2018-00760; 2015-0922; P30CA016672
• First Posted: Apr 4, 2018
• Last Update Posted: Apr 13, 2021
• Last Verified: Mar 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes
• Additional relevant MeSH terms: Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Philadelphia Chromosome; Calcium, Dietary; Leucovorin; Folic Acid; Cytarabine; Dexamethasone; Prednisone; Dexamethasone acetate; Cortisone; Cyclophosphamide; Rituximab; Doxorubicin; Liposomal doxorubicin; Methotrexate; Vincristine; Mercaptopurine; Ofatumumab; Inotuzumab Ozogamicin; Antineoplastic Agents, Immunological; Antibodies; Immunoglobulins; Antibodies, Monoclonal; BB 1101; Calcium; Levoleucovorin

Study Results

Participant Flow

Recruitment Details	Recruitment Period: March 2018 to January 2019

Arm/Group Title	Treatment (Hyper-CVAD, Inotuzumab Ozogamicin)
Arm/Group Description	See detailed description. Cyclophosphamide: Given IV Cytarabine: Given IT or IV Dexamethasone: Given IV or PO Doxorubicin Hydrochloride: Given IV Inotuzumab Ozogamicin: Given IV Laboratory Biomarker Analysis: Correlative studies Leucovorin Calcium: Given IV Mercaptopurine: Given PO Methotrexate: Given IT, IV or PO Ofatumumab: Given IV Prednisone: Given PO Rituximab: Given IV Vincristine Sulfate: Given IV
Period Title: Overall Study
STARTED	4
COMPLETED	0
NOT COMPLETED	4

Baseline Characteristics

Arm/Group Title	Treatment (Hyper-CVAD, Inotuzumab Ozogamicin)
Arm/Group Description	See detailed description. Cyclophosphamide: Given IV Cytarabine: Given IT or IV Dexamethasone: Given IV or PO Doxorubicin Hydrochloride: Given IV Inotuzumab Ozogamicin: Given IV Laboratory Biomarker Analysis: Correlative studies Leucovorin Calcium: Given IV Mercaptopurine: Given PO Methotrexate: Given IT, IV or PO Ofatumumab: Given IV Prednisone: Given PO Rituximab: Given IV Vincristine Sulfate: Given IV
Overall Participants	4
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	4 100%
>=65 years	0 0%
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	29
Sex: Female, Male (Count of Participants)
Female	2 50%
Male	2 50%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	3 75%
More than one race	0 0%
Unknown or Not Reported	1 25%
Region of Enrollment (participants) [Number]
United States	4 100%

Outcome Measures

1. Primary Outcome

Title	Event-Free Survival
Description	Event-free survival defined as the time interval from date of treatment start until the date of death, disease progression or relapse.
Time Frame	Start of treatment up to 2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Hyper-CVAD, Inotuzumab Ozogamicin)
Arm/Group Description	See detailed description. Cyclophosphamide: Given IV Cytarabine: Given IT or IV Dexamethasone: Given IV or PO Doxorubicin Hydrochloride: Given IV Inotuzumab Ozogamicin: Given IV Laboratory Biomarker Analysis: Correlative studies Leucovorin Calcium: Given IV Mercaptopurine: Given PO Methotrexate: Given IT, IV or PO Ofatumumab: Given IV Prednisone: Given PO Rituximab: Given IV Vincristine Sulfate: Given IV
Measure Participants	4
Median (Full Range) [Months]	24

2. Secondary Outcome

Title	Overall Survival
Description	Time from date of treatment start until date of death due to any cause or last Follow-up.
Time Frame	Start of treatment up to 2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Hyper-CVAD, Inotuzumab Ozogamicin)
Arm/Group Description	See detailed description. Cyclophosphamide: Given IV Cytarabine: Given IT or IV Dexamethasone: Given IV or PO Doxorubicin Hydrochloride: Given IV Inotuzumab Ozogamicin: Given IV Laboratory Biomarker Analysis: Correlative studies Leucovorin Calcium: Given IV Mercaptopurine: Given PO Methotrexate: Given IT, IV or PO Ofatumumab: Given IV Prednisone: Given PO Rituximab: Given IV Vincristine Sulfate: Given IV
Measure Participants	4
Median (Full Range) [Months]	24

3. Secondary Outcome

Title	Participants to Achieve Complete Remission (CR):
Description	Complete Remission (CR) is defined as - Normalization of the peripheral blood and bone marrow blasts </= 5% in normocellular or hypercellular marrow, granulocyte count of 1x10^9/L or above and platelets >/= 100X10^9/L and complete resolution of all sites of extramedullary disease.
Time Frame	Start of treatment up to 2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Hyper-CVAD, Inotuzumab Ozogamicin)
Arm/Group Description	See detailed description. Cyclophosphamide: Given IV Cytarabine: Given IT or IV Dexamethasone: Given IV or PO Doxorubicin Hydrochloride: Given IV Inotuzumab Ozogamicin: Given IV Laboratory Biomarker Analysis: Correlative studies Leucovorin Calcium: Given IV Mercaptopurine: Given PO Methotrexate: Given IT, IV or PO Ofatumumab: Given IV Prednisone: Given PO Rituximab: Given IV Vincristine Sulfate: Given IV
Measure Participants	4
Count of Participants [Participants]	4 100%

4. Secondary Outcome

Title	Number of Participants With Minimal Residual Disease (MRD) Negativity
Description	MRD levels continuously assessed during induction and consolidation therapy by 6-color multiparameter flow. MRD negativity defined by a value of at least 10-4 and confirmed on a second bone marrow aspiration/biopsy performed after a subsequent cycle.
Time Frame	Start of treatment up to 2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Hyper-CVAD, Inotuzumab Ozogamicin)
Arm/Group Description	See detailed description. Cyclophosphamide: Given IV Cytarabine: Given IT or IV Dexamethasone: Given IV or PO Doxorubicin Hydrochloride: Given IV Inotuzumab Ozogamicin: Given IV Laboratory Biomarker Analysis: Correlative studies Leucovorin Calcium: Given IV Mercaptopurine: Given PO Methotrexate: Given IT, IV or PO Ofatumumab: Given IV Prednisone: Given PO Rituximab: Given IV Vincristine Sulfate: Given IV
Measure Participants	4
Count of Participants [Participants]	4 100%

5. Secondary Outcome

Title	Number of Participants With Adverse Events
Description	For the purpose of toxicity monitoring, toxicities are defined as any treatment -related grade 3 or 4 non-hematologic AEs occurred any time during the trial.NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 utilized for adverse event reporting.
Time Frame	Start of treatment up to 30 days after last dose received.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Hyper-CVAD, Inotuzumab Ozogamicin)
Arm/Group Description	See detailed description. Cyclophosphamide: Given IV Cytarabine: Given IT or IV Dexamethasone: Given IV or PO Doxorubicin Hydrochloride: Given IV Inotuzumab Ozogamicin: Given IV Laboratory Biomarker Analysis: Correlative studies Leucovorin Calcium: Given IV Mercaptopurine: Given PO Methotrexate: Given IT, IV or PO Ofatumumab: Given IV Prednisone: Given PO Rituximab: Given IV Vincristine Sulfate: Given IV
Measure Participants	4
Neutropenic Fever	2 50%
Peripheral Sensory Neuropathy	1 25%
Allergic Reaction	1 25%
Muscle Weakness	1 25%

Adverse Events

Time Frame	Up to 2 years
Arm/Group Title	Treatment (Hyper-CVAD, Inotuzumab Ozogamicin)
Arm/Group Description	See detailed description. Cyclophosphamide: Given IV Cytarabine: Given IT or IV Dexamethasone: Given IV or PO Doxorubicin Hydrochloride: Given IV Inotuzumab Ozogamicin: Given IV Laboratory Biomarker Analysis: Correlative studies Leucovorin Calcium: Given IV Mercaptopurine: Given PO Methotrexate: Given IT, IV or PO Ofatumumab: Given IV Prednisone: Given PO Rituximab: Given IV Vincristine Sulfate: Given IV
All Cause Mortality
	Treatment (Hyper-CVAD, Inotuzumab Ozogamicin)
	Affected / at Risk (%)	# Events
Total	0/4 (0%)
Serious Adverse Events
	Treatment (Hyper-CVAD, Inotuzumab Ozogamicin)
	Affected / at Risk (%)	# Events
Total	3/4 (75%)
Blood and lymphatic system disorders
Neutropenic Fever	2/4 (50%)	2
General disorders
Fever	2/4 (50%)	2
Infections and infestations
Kidney Infection	1/4 (25%)	1
Musculoskeletal and connective tissue disorders
Muscle Weakness	1/4 (25%)	1
Other (Not Including Serious) Adverse Events
	Treatment (Hyper-CVAD, Inotuzumab Ozogamicin)
	Affected / at Risk (%)	# Events
Total	4/4 (100%)
Cardiac disorders
Sinus Bradycardia	2/4 (50%)	2
Eye disorders
Blurred Vision	1/4 (25%)	1
Gastrointestinal disorders
Abdominal Pain	2/4 (50%)	2
Anorexia	1/4 (25%)	1
Constipation	2/4 (50%)	2
Diarrhea	1/4 (25%)	1
Nausea	2/4 (50%)	2
Oral Mucositis	3/4 (75%)	4
Vomiting	2/4 (50%)	2
General disorders
Edema Limbs	1/4 (25%)	1
Fatigue	1/4 (25%)	1
Infusion Related Reaction	2/4 (50%)	2
Non-Cardiac Chest Pain	2/4 (50%)	2
Pain	1/4 (25%)	2
Gait Disturbance	1/4 (25%)	1
Immune system disorders
Allergic Reaction	2/4 (50%)	2
Investigations
Alanine Aminotransferase Increased	2/4 (50%)	3
Neutropenia	3/4 (75%)	3
Thrombocytopenia	3/4 (75%)	3
Metabolism and nutrition disorders
Hypokalemia	1/4 (25%)	1
Hyponatremia	1/4 (25%)	1
Nervous system disorders
Headache	3/4 (75%)	3
Peripheral Sensory Neuropathy	4/4 (100%)	4
Arachnoiditis	1/4 (25%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnea	1/4 (25%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.