Combination Chemotherapy and Ofatumumab in Treating Patients With Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma

• Sponsor: M.D. Anderson Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT01363128
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 72
• Location: 1
• Arm: 1
• Actual Duration (Months): 104.9
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

This phase II trial studies how well combination chemotherapy and ofatumumab work in treating patients with acute lymphoblastic leukemia or lymphoblastic lymphoma. Drugs used in chemotherapy, such as cyclophosphamide, vincristine sulfate, doxorubicin hydrochloride, and dexamethasone, 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. Immunotherapy with ofatumumab, may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Giving combination chemotherapy together with ofatumumab may be an effective treatment for acute lymphoblastic leukemia or lymphoblastic lymphoma.

Condition or Disease	Intervention/Treatment	Phase
Acute Lymphoblastic Leukemia; Adult Acute Lymphoblastic Leukemia in Complete Remission; Burkitt Leukemia; Burkitt Lymphoma; CD20 Positive; Childhood Acute Lymphoblastic Leukemia in Complete Remission; Lymphoblastic Lymphoma	Drug: Cyclophosphamide; Drug: Cytarabine; Drug: Dexamethasone; Drug: Doxorubicin Hydrochloride; Other: Laboratory Biomarker Analysis; Drug: Methotrexate; Biological: Ofatumumab; Drug: Vincristine Sulfate	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. To evaluate the clinical efficacy of the combination of hyper-CVAD (cyclophosphamide, vincristine sulfate, doxorubicin hydrochloride, and dexamethasone) + ofatumumab in patients with newly diagnosed acute lymphoblastic leukemia with any level of CD20 expression: event-free survival; overall response rate; overall survival.

SECONDARY OBJECTIVES:

1. To evaluate the safety of this combination.

OUTLINE:

COURSES 1, 3, 5, 7: Patients receive hyper-CVAD comprising cyclophosphamide intravenously (IV) over 3 hours every 12 hours on days 1-3; doxorubicin hydrochloride IV over 24 hours on day 4; vincristine sulfate IV over 15 minutes on days 4 and 11; and dexamethasone IV over 30 minutes or orally (PO) once daily (QD) on days 1-4 and 11-14. Patients also receive ofatumumab IV over 4-6 hours on days 1 and 11 of courses 1 and 3.

COURSES 2, 4, 6, 8: Patients receive high-dose methotrexate IV over 2 hours and then over 22 hours on day 1 and cytarabine IV over 2 hours every 12 hours on days 2-3. Patients also receive ofatumumab IV over 4-6 hours on days 1 and 8 of courses 2 and 4.

Treatment repeats every 21-28 days for 8 courses in the absence of disease progression or unacceptable toxicity. Patients may receive maintenance therapy for an additional 30 months.

After completion of study treatment, patients are followed up at 30 days and then every 3 months for 1 year.

Study Design

• Study Type: Interventional
• Actual Enrollment: 72 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 Combination With Ofatumumab as Frontline Therapy for Patients With CD-20 Positive Acute Lymphoblastic Leukemia
• Actual Study Start Date: Jul 12, 2011
• Actual Primary Completion Date: Apr 8, 2020
• Actual Study Completion Date: Apr 8, 2020

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Treatment (hyper-CVAD, ofatumumab) COURSES 1, 3, 5, 7: Patients receive hyper-CVAD comprising cyclophosphamide IV over 3 hours every 12 hours on days 1-3; doxorubicin hydrochloride IV over 24 hours on day 4; vincristine sulfate IV over 15 minutes on days 4 and 11; and dexamethasone IV over 30 minutes or PO QD on days 1-4 and 11-14. Patients also receive ofatumumab IV over 4-6 hours on days 1 and 11 of courses 1 and 3. COURSES 2, 4, 6, 8: Patients receive high-dose methotrexate IV over 2 hours and then over 22 hours on day 1 and cytarabine IV over 2 hours every 12 hours on days 2-3. Patients also receive ofatumumab IV over 4-6 hours on days 1 and 8 of courses 2 and 4. Treatment repeats every 21-28 days for 8 courses in the absence of disease progression or unacceptable toxicity. Patients may receive maintenance therapy for an additional 30 months.

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 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 ; Other: Laboratory Biomarker Analysis; Correlative studies; Drug: Methotrexate; Given IV; 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: Vincristine Sulfate; Given IV; Other Names: Kyocristine Leurocristine sulfate Leurocristine, sulfate Oncovin Vincasar Vincosid Vincrex Vincristine, sulfate

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Complete Remission (CR) [Up to 8 years]

   Complete Remission is Normalization of the peripheral blood and bone marrow with 5% or less blasts in marrow with a granulocyte count of 1 x 109/L or above and a platelet count of 100x 109/L or above. Complete resolution of all sites of extramedullary disease is required for CR.

2. 4-Year Overall Survival [Up to 4 years]

   Overall Survival is defined as time from date of treatment start until date of death due to any cause or last Follow-up. For continuous data, summary statistics including n, mean, standard deviation, median, minimum and maximum will be computed. The posterior median time to event and it 95% credible interval will be estimated. Kaplan-Meier method, Log rank test and Cox proportional hazards regression modeling will be utilized to analyze survival at 4 years.

3. 4-year Event Free Survival [Up to 4 years]

   Event Free Survival defined as the time from the start of therapy to time of primary refractory disease, relapse from CR, death from any cause or last follow-up. Kaplan-Meier method will be utilized to analyze event free survival for the 4 year percent alive and in CR.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients of all ages with newly diagnosed, previously untreated CD-20+ acute lymphoblastic leukemia (ALL), or lymphoblastic lymphoma, Burkitt leukemia/lymphoma or having achieved complete remission (CR) with one course of induction chemotherapy

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

• Performance status of 0, 1, or 2

• Creatinine less than or equal to 3.0 mg/dL (unless considered tumor related)

• Bilirubin less than or equal to 3.0 mg/dL (unless considered tumor related)

• Adequate cardiac function defined as no clinically significant history of arrhythmia as determined by the principal investigator (PI) and/or the treating physician, history of myocardial infarction (MI) or clinically significant abnormal electrocardiogram (EKG), as determined by the PI and/or the treating physician, within 3 months prior to study enrollment; cardiac function will be assessed by history and physical examination

• No active or co-existing malignancy (other than ALL or lymphoblastic lymphoma) with life expectancy less than 12 months due to that malignancy

Exclusion Criteria:

• Pregnant or nursing women

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

• Philadelphia chromosome (Ph)+ 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 metastases or stable chronic liver disease per investigator assessment)

• Treatment with any known non-marketed drug substance or experimental therapy within 5 terminal half-lives (calculated by multiplying the reported terminal half-life by 5) or 4 weeks prior to enrollment, whichever is longer, or currently participating in any other interventional clinical study

• History of significant cerebrovascular disease in the past 6 months or ongoing event with active symptoms or sequelae

• Positive serology for hepatitis B (HB) defined as a positive test for hepatitis B surface antigen (HBsAg); in addition, if negative for HBsAg but hepatitis B core antibody (HBcAb) positive (regardless of HBsAb status), a HB deoxyribonucleic acid (DNA) test will be performed and if positive the subject will be excluded; consult with a physician experienced in care & management of subjects with hepatitis B to manage/treat subjects who are anti-HBc positive

• Positive serology for hepatitis C (HC) defined as a positive test for hepatitis C antibody (HCAb), in which case reflexively perform a HC radioimmunoblotting assay (RIBA) immunoblot assay on the same sample to confirm the result

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 - Nov 5, 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: NCT01363128
• Other Study ID Numbers: 2010-0708; NCI-2011-01061; 2010-0708
• First Posted: Jun 1, 2011
• Last Update Posted: May 3, 2021
• Last Verified: Apr 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Burkitt Lymphoma; Lymphoma; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Cytarabine; Dexamethasone; Dexamethasone acetate; Cyclophosphamide; Doxorubicin; Liposomal doxorubicin; Methotrexate; Vincristine; Ofatumumab; Antibodies, Monoclonal; BB 1101

Study Results

Participant Flow

Recruitment Details	Recruitment Period: August 2011 to May 2017

Arm/Group Title	Treatment (Hyper-CVAD, Ofatumumab)
Arm/Group Description	COURSES 1, 3, 5, 7: Patients receive hyper-CVAD comprising cyclophosphamide IV over 3 hours every 12 hours on days 1-3; doxorubicin hydrochloride IV over 24 hours on day 4; vincristine sulfate IV over 15 minutes on days 4 and 11; and dexamethasone IV over 30 minutes or PO QD on days 1-4 and 11-14. Patients also receive ofatumumab IV over 4-6 hours on days 1 and 11 of courses 1 and 3. COURSES 2, 4, 6, 8: Patients receive high-dose methotrexate IV over 2 hours and then over 22 hours on day 1 and cytarabine IV over 2 hours every 12 hours on days 2-3. Patients also receive ofatumumab IV over 4-6 hours on days 1 and 8 of courses 2 and 4. Treatment repeats every 21-28 days for 8 courses in the absence of disease progression or unacceptable toxicity. Patients may receive maintenance therapy for an additional 30 months. Cyclophosphamide: Given IV Cytarabine: Given IV Dexamethasone: Given IV or PO Doxorubicin Hydrochloride: Given IV Laboratory Biomarker Analysis: Correlative studies Methotrexate: Given IV Ofatumumab: Given IV Vincristine Sulfate: Given IV
Period Title: Overall Study
STARTED	69
COMPLETED	69
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Treatment (Hyper-CVAD, Ofatumumab)
Arm/Group Description	COURSES 1, 3, 5, 7: Patients receive hyper-CVAD comprising cyclophosphamide IV over 3 hours every 12 hours on days 1-3; doxorubicin hydrochloride IV over 24 hours on day 4; vincristine sulfate IV over 15 minutes on days 4 and 11; and dexamethasone IV over 30 minutes or PO QD on days 1-4 and 11-14. Patients also receive ofatumumab IV over 4-6 hours on days 1 and 11 of courses 1 and 3. COURSES 2, 4, 6, 8: Patients receive high-dose methotrexate IV over 2 hours and then over 22 hours on day 1 and cytarabine IV over 2 hours every 12 hours on days 2-3. Patients also receive ofatumumab IV over 4-6 hours on days 1 and 8 of courses 2 and 4. Treatment repeats every 21-28 days for 8 courses in the absence of disease progression or unacceptable toxicity. Patients may receive maintenance therapy for an additional 30 months. Cyclophosphamide: Given IV Cytarabine: Given IV Dexamethasone: Given IV or PO Doxorubicin Hydrochloride: Given IV Laboratory Biomarker Analysis: Correlative studies Methotrexate: Given IV Ofatumumab: Given IV Vincristine Sulfate: Given IV
Overall Participants	69
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	68 98.6%
>=65 years	1 1.4%
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	41
Sex: Female, Male (Count of Participants)
Female	29 42%
Male	40 58%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	3 4.3%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	3 4.3%
White	53 76.8%
More than one race	0 0%
Unknown or Not Reported	10 14.5%
Region of Enrollment (participants) [Number]
United States	69 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Complete Remission (CR)
Description	Complete Remission is Normalization of the peripheral blood and bone marrow with 5% or less blasts in marrow with a granulocyte count of 1 x 109/L or above and a platelet count of 100x 109/L or above. Complete resolution of all sites of extramedullary disease is required for CR.
Time Frame	Up to 8 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Hyper-CVAD, Ofatumumab)
Arm/Group Description	COURSES 1, 3, 5, 7: Patients receive hyper-CVAD comprising cyclophosphamide IV over 3 hours every 12 hours on days 1-3; doxorubicin hydrochloride IV over 24 hours on day 4; vincristine sulfate IV over 15 minutes on days 4 and 11; and dexamethasone IV over 30 minutes or PO QD on days 1-4 and 11-14. Patients also receive ofatumumab IV over 4-6 hours on days 1 and 11 of courses 1 and 3. COURSES 2, 4, 6, 8: Patients receive high-dose methotrexate IV over 2 hours and then over 22 hours on day 1 and cytarabine IV over 2 hours every 12 hours on days 2-3. Patients also receive ofatumumab IV over 4-6 hours on days 1 and 8 of courses 2 and 4. Treatment repeats every 21-28 days for 8 courses in the absence of disease progression or unacceptable toxicity. Patients may receive maintenance therapy for an additional 30 months. Cyclophosphamide: Given IV Cytarabine: Given IV Dexamethasone: Given IV or PO Doxorubicin Hydrochloride: Given IV Laboratory Biomarker Analysis: Correlative studies Methotrexate: Given IV Ofatumumab: Given IV Vincristine Sulfate: Given IV
Measure Participants	69
Count of Participants [Participants]	68 98.6%

2. Primary Outcome

Title	4-Year Overall Survival
Description	Overall Survival is defined as time from date of treatment start until date of death due to any cause or last Follow-up. For continuous data, summary statistics including n, mean, standard deviation, median, minimum and maximum will be computed. The posterior median time to event and it 95% credible interval will be estimated. Kaplan-Meier method, Log rank test and Cox proportional hazards regression modeling will be utilized to analyze survival at 4 years.
Time Frame	Up to 4 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Hyper-CVAD, Ofatumumab)
Arm/Group Description	COURSES 1, 3, 5, 7: Patients receive hyper-CVAD comprising cyclophosphamide IV over 3 hours every 12 hours on days 1-3; doxorubicin hydrochloride IV over 24 hours on day 4; vincristine sulfate IV over 15 minutes on days 4 and 11; and dexamethasone IV over 30 minutes or PO QD on days 1-4 and 11-14. Patients also receive ofatumumab IV over 4-6 hours on days 1 and 11 of courses 1 and 3. COURSES 2, 4, 6, 8: Patients receive high-dose methotrexate IV over 2 hours and then over 22 hours on day 1 and cytarabine IV over 2 hours every 12 hours on days 2-3. Patients also receive ofatumumab IV over 4-6 hours on days 1 and 8 of courses 2 and 4. Treatment repeats every 21-28 days for 8 courses in the absence of disease progression or unacceptable toxicity. Patients may receive maintenance therapy for an additional 30 months. Cyclophosphamide: Given IV Cytarabine: Given IV Dexamethasone: Given IV or PO Doxorubicin Hydrochloride: Given IV Laboratory Biomarker Analysis: Correlative studies Methotrexate: Given IV Ofatumumab: Given IV Vincristine Sulfate: Given IV
Measure Participants	69
Count of Participants [Participants]	47 68.1%

3. Primary Outcome

Title	4-year Event Free Survival
Description	Event Free Survival defined as the time from the start of therapy to time of primary refractory disease, relapse from CR, death from any cause or last follow-up. Kaplan-Meier method will be utilized to analyze event free survival for the 4 year percent alive and in CR.
Time Frame	Up to 4 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Hyper-CVAD, Ofatumumab)
Arm/Group Description	COURSES 1, 3, 5, 7: Patients receive hyper-CVAD comprising cyclophosphamide IV over 3 hours every 12 hours on days 1-3; doxorubicin hydrochloride IV over 24 hours on day 4; vincristine sulfate IV over 15 minutes on days 4 and 11; and dexamethasone IV over 30 minutes or PO QD on days 1-4 and 11-14. Patients also receive ofatumumab IV over 4-6 hours on days 1 and 11 of courses 1 and 3. COURSES 2, 4, 6, 8: Patients receive high-dose methotrexate IV over 2 hours and then over 22 hours on day 1 and cytarabine IV over 2 hours every 12 hours on days 2-3. Patients also receive ofatumumab IV over 4-6 hours on days 1 and 8 of courses 2 and 4. Treatment repeats every 21-28 days for 8 courses in the absence of disease progression or unacceptable toxicity. Patients may receive maintenance therapy for an additional 30 months. Cyclophosphamide: Given IV Cytarabine: Given IV Dexamethasone: Given IV or PO Doxorubicin Hydrochloride: Given IV Laboratory Biomarker Analysis: Correlative studies Methotrexate: Given IV Ofatumumab: Given IV Vincristine Sulfate: Given IV
Measure Participants	69
Count of Participants [Participants]	41 59.4%

Adverse Events

Time Frame	Up to 8 years 9 months
Arm/Group Title	Treatment (Hyper-CVAD, Ofatumumab)
Arm/Group Description	COURSES 1, 3, 5, 7: Patients receive hyper-CVAD comprising cyclophosphamide IV over 3 hours every 12 hours on days 1-3; doxorubicin hydrochloride IV over 24 hours on day 4; vincristine sulfate IV over 15 minutes on days 4 and 11; and dexamethasone IV over 30 minutes or PO QD on days 1-4 and 11-14. Patients also receive ofatumumab IV over 4-6 hours on days 1 and 11 of courses 1 and 3. COURSES 2, 4, 6, 8: Patients receive high-dose methotrexate IV over 2 hours and then over 22 hours on day 1 and cytarabine IV over 2 hours every 12 hours on days 2-3. Patients also receive ofatumumab IV over 4-6 hours on days 1 and 8 of courses 2 and 4. Treatment repeats every 21-28 days for 8 courses in the absence of disease progression or unacceptable toxicity. Patients may receive maintenance therapy for an additional 30 months. Cyclophosphamide: Given IV Cytarabine: Given IV Dexamethasone: Given IV or PO Doxorubicin Hydrochloride: Given IV Laboratory Biomarker Analysis: Correlative studies Methotrexate: Given IV Ofatumumab: Given IV Vincristine Sulfate: Given IV
All Cause Mortality
	Treatment (Hyper-CVAD, Ofatumumab)
	Affected / at Risk (%)	# Events
Total	1/69 (1.4%)
Serious Adverse Events
	Treatment (Hyper-CVAD, Ofatumumab)
	Affected / at Risk (%)	# Events
Total	46/69 (66.7%)
Blood and lymphatic system disorders
Anemia	1/69 (1.4%)	1
Neutropenic Fever	10/69 (14.5%)	13
Cardiac disorders
Sinus Tachycardia	2/69 (2.9%)	2
Ear and labyrinth disorders
Ear Other	1/69 (1.4%)	1
Eye disorders
Eye Disorders	1/69 (1.4%)	1
Gastrointestinal disorders
Colitis	1/69 (1.4%)	1
Constipation	3/69 (4.3%)	3
Dehydration	1/69 (1.4%)	1
Diarrhea	1/69 (1.4%)	1
Gastric Hemorrhage	1/69 (1.4%)	1
Gastrointestinal Disorder	3/69 (4.3%)	4
Ileus	1/69 (1.4%)	1
Nausea	1/69 (1.4%)	1
Oral Hemorrhage	1/69 (1.4%)	1
Pancreatitis	1/69 (1.4%)	1
Rectal Hemorrhage	1/69 (1.4%)	1
Vomiting	2/69 (2.9%)	2
General disorders
Fever	7/69 (10.1%)	8
Headache	2/69 (2.9%)	2
Infusion Related Reaction	1/69 (1.4%)	1
Pain	5/69 (7.2%)	5
Hepatobiliary disorders
Cholecyisitis	1/69 (1.4%)	1
Infections and infestations
Appendicitis	1/69 (1.4%)	1
Cellulitis	1/69 (1.4%)	1
Infection	30/69 (43.5%)	59
Lung Infection	15/69 (21.7%)	26
Meningitis	1/69 (1.4%)	1
Sepsis	9/69 (13%)	11
Sinusitis	3/69 (4.3%)	4
Injury, poisoning and procedural complications
Fall	1/69 (1.4%)	1
Fracture	1/69 (1.4%)	1
Postoperative Hemorrhage	1/69 (1.4%)	1
Investigations
Alanine Aminotransferase Increased	2/69 (2.9%)	2
Metabolism and nutrition disorders
Muscle Weakness	1/69 (1.4%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasm benign, malignant	1/69 (1.4%)	1
Treatment Related Secondary Malignancy	1/69 (1.4%)	1
Nervous system disorders
Nervous System Disorder	1/69 (1.4%)	2
Syncope	1/69 (1.4%)	1
Renal and urinary disorders
Renal and Urinary Disorders	1/69 (1.4%)	1
Reproductive system and breast disorders
Reproductive System and Breast Disorders	1/69 (1.4%)	1
Respiratory, thoracic and mediastinal disorders
Dyspena	1/69 (1.4%)	1
Epistaxis	1/69 (1.4%)	1
Skin and subcutaneous tissue disorders
Erythema Multiforme	1/69 (1.4%)	1
Skin Lesion	1/69 (1.4%)	1
Vascular disorders
Hypotension	3/69 (4.3%)	3
Peripheral Ischemia	1/69 (1.4%)	1
Thromboembolic Event	1/69 (1.4%)	1
Other (Not Including Serious) Adverse Events
	Treatment (Hyper-CVAD, Ofatumumab)
	Affected / at Risk (%)	# Events
Total	48/69 (69.6%)
Blood and lymphatic system disorders
Anemia	11/69 (15.9%)	21
Gastrointestinal disorders
Constipation	5/69 (7.2%)	5
Diarrhea	6/69 (8.7%)	7
Oral Mucositis	6/69 (8.7%)	7
Nausea	13/69 (18.8%)	17
Vomiting	8/69 (11.6%)	10
General disorders
Fever	7/69 (10.1%)	7
Headache	7/69 (10.1%)	8
Pain in Extremity	4/69 (5.8%)	9
Infections and infestations
Catheter Related Infection	4/69 (5.8%)	5
Neutropenic Fever	10/69 (14.5%)	10
Infection	8/69 (11.6%)	10
Sepsis	4/69 (5.8%)	4
Skin Infection	4/69 (5.8%)	4
Upper Respiratory Infection	5/69 (7.2%)	7
Investigations
Alanine Aminotransferase Increased	14/69 (20.3%)	22
Aspartate Aminotransferase Increased	5/69 (7.2%)	5
Blood Bilirubin Increased	4/69 (5.8%)	4
Infusion Related Reaction	12/69 (17.4%)	13
Neutropenia	19/69 (27.5%)	57
Thrombocytopenia	17/69 (24.6%)	45
Metabolism and nutrition disorders
Hyperglycemia	12/69 (17.4%)	21
Nervous system disorders
Insomnia	4/69 (5.8%)	4
Peripheral Sensory Neuropathy	4/69 (5.8%)	7
Skin and subcutaneous tissue disorders
Alopecia	4/69 (5.8%)	4

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.