Phase II Study of Dose-Adjusted EPOCH-Rituximab in Adults With Untreated Burkitt Lymphoma and c-MYC+ Diffuse Large B-Cell Lymphoma

• ClinicalTrials.gov Identifier: NCT01092182
• Recruitment Status: Active, not recruiting
• First Posted: March 24, 2010
• Results First Posted: October 19, 2021
• Last Update Posted: November 9, 2022
• Sponsor: National Cancer Institute (NCI)
• Information provided by (Responsible Party): Mark Roschewski, M.D., National Cancer Institute (NCI)

• Study Type: Interventional
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Conditions: Burkitt Lymphoma; Diffuse Large B-cell Lymphoma, c-MYC Positive; Plasmablastic Lymphoma
• Interventions: Drug: EPOCH-R; Drug: EPOCH-RR
• Enrollment: 194

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Low-risk Burkitt Lymphoma (BL)	High-Risk Burkitt Lymphoma (BL)	High-Risk Diffuse Large B Cell Lymphoma (DLBCL)
Arm/Group Description	Burkitt lymphoma Low Risk Arm Etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH-R) every 21 days for 6 cycles	Burkitt lymphoma High Risk Arm Etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH-R) every 21 days for 6 cycles	High-Risk Diffuse Large B Cell Lymphoma Etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH-R) every 21 days for 6 cycles
Period Title: Overall Study
Started	15	98	81
Completed	14	80	53
Not Completed	1	18	28
Reason Not Completed
Death	0	5	3
participant safety	1	2	0
Physician Decision	0	6	0
Did not meet criteria	0	0	25
Non-compliance	0	3	0
Participant refused follow-up	0	2	0

Baseline Characteristics

Arm/Group Title		Group A - Low-risk Burkitt Lymphoma (BL)	Group B - High-Risk Burkitt Lymphoma (BL)	Group C - High-Risk Diffuse Large B Cell Lymphoma (DLBCL)	Total
Arm/Group Description		Burkitt lymphoma Low Risk Arm Etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH-R) every 21 days for 6 cycles	Burkitt lymphoma High Risk Arm Etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH-R) every 21 days for 6 cycles	Diffuse large B-cell lymphoma (DLBCL) high risk arm Etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH-R) every 21 days for 6 cycles	Total of all reporting groups
Overall Number of Baseline Participants		15	98	81	194
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	15 participants	98 participants	81 participants	194 participants
	<=18 years	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Between 18 and 65 years	13 86.7%	84 85.7%	55 67.9%	152 78.4%
	>=65 years	2 13.3%	14 14.3%	26 32.1%	42 21.6%
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	15 participants	98 participants	81 participants	194 participants
		51.47 (14.85)	46.35 (17.53)	57.47 (14)	51.39 (16.74)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	15 participants	98 participants	81 participants	194 participants
	Female	4 26.7%	20 20.4%	20 24.7%	44 22.7%
	Male	11 73.3%	78 79.6%	61 75.3%	150 77.3%
Race/Ethnicity, Customized; Measure Type: Count of Participants; Unit of measure: Participants	Number Analyzed	15 participants	98 participants	81 participants	194 participants
Black or African American		2 13.3%	16 16.3%	6 7.4%	24 12.4%
White		11 73.3%	65 66.3%	66 81.5%	142 73.2%
Indian or Alaska Native		1 6.7%	0 0.0%	0 0.0%	1 0.5%
Indian or Alaska Native + White		0 0.0%	1 1.0%	0 0.0%	1 0.5%
Asian		1 6.7%	5 5.1%	2 2.5%	8 4.1%
Race Unknown/Not Reported		0 0.0%	11 11.2%	7 8.6%	18 9.3%
Hispanic or Latino		1 6.7%	10 10.2%	4 4.9%	15 7.7%
Not Hispanic or Latino		14 93.3%	80 81.6%	72 88.9%	166 85.6%
Ethnicity Unknown/Not Reported		0 0.0%	8 8.2%	5 6.2%	13 6.7%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
United States	Number Analyzed	15 participants	98 participants	81 participants	194 participants
		15	98	81	194
Eastern Cooperative Oncology Group (ECOG) [1]; Measure Type: Count of Participants; Unit of measure: Participants	Number Analyzed	15 participants	98 participants	81 participants	194 participants
0		11 73.3%	39 39.8%	26 32.1%	76 39.2%
1		4 26.7%	38 38.8%	37 45.7%	79 40.7%
2		0 0.0%	14 14.3%	9 11.1%	23 11.9%
3		0 0.0%	4 4.1%	7 8.6%	11 5.7%
4		0 0.0%	3 3.1%	2 2.5%	5 2.6%
		[1] Measure Description: ECOG Criteria: 0 - Normal activity; - Symptoms, but ambulatory.; - In bed <50% of the time.; - In bed >50% of the time.; - 100% bedridden.
Baseline Risk Stratification [1]; Measure Type: Count of Participants; Unit of measure: Participants	Number Analyzed	15 participants	98 participants	81 participants	194 participants
Low Risk		15 100.0%	0 0.0%	0 0.0%	15 7.7%
High Risk		0 0.0%	98 100.0%	81 100.0%	179 92.3%
		[1] Measure Description: Low Risk disease High Risk disease
International Prognostic Index Score 0-5 [1]; Measure Type: Count of Participants; Unit of measure: Participants	Number Analyzed	15 participants	98 participants	81 participants	194 participants
0		12 80.0%	8 8.2%	7 8.6%	27 13.9%
1		3 20.0%	19 19.4%	7 8.6%	29 14.9%
2		0 0.0%	20 20.4%	28 34.6%	48 24.7%
3		0 0.0%	24 24.5%	30 37.0%	54 27.8%
4		0 0.0%	24 24.5%	5 6.2%	29 14.9%
5		0 0.0%	3 3.1%	4 4.9%	7 3.6%
		[1] Measure Description: International Prognostic Index Score 0 -1 is low risk 2 is low-intermediate risk 3 is high-intermediate risk 4 - 5 is high risk
Histology; Measure Type: Count of Participants; Unit of measure: Participants	Number Analyzed	15 participants	98 participants	81 participants	194 participants
High Grade B Cell Lymphoma Double-hit (HGBL DH)		NA [1]	NA [1]	24 29.6%	NA [2]
High Grade B Cell Lymphoma Not Otherwise Specified (HGBL NOS)		NA [1]	NA [1]	12 14.8%	NA [2]
Diffuse Large B-Cell Lymphoma (DLBCL)		NA [1]	NA [1]	44 54.3%	NA [2]
Plasmablastic		NA [1]	NA [1]	1 1.2%	NA [2]
		[1] This study specific measure is only applicable to Group C.; [2] Total not calculated because data are not available (NA) in one or more arms.

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Kaplan-Meier Curve Progression Free Survival (PFS) Constructed With an 95% Confidence Interval
Description	PFS is the time interval from start of treatment to documented evidence of disease progression. Disease progression was measured by the International Workshop Criteria (IWC). Progression is a positive positron emission tomography (PET) finding corresponding to the computed tomography (CT) abnormality (new lesion, increasing size of previous lesion), or a negative PET and a CT abnormality (new lesion, increasing size of previous lesion) of < 1.5 cm (< 1.0 cm in the lungs). Kaplan-Meier curves were constructed with an 95% confidence interval.
Time Frame	Time of progression or death at 4 years

Outcome Measure Data

Analysis Population Description

Those participants that were not analyzed for PFS were screen failures (did not have MYC+ Diffuse Large B-Cell Lymphoma (DLBCL).

Arm/Group Title	Group A - Low-risk Burkitt Lymphoma (BL)	Group B - High-Risk Burkitt Lymphoma (BL)	Group C - High-Risk Diffuse Large B Cell Lymphoma (DLBCL)
Arm/Group Description:	Burkitt lymphoma Low Risk Arm Etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH-R) every 21 days for 6 cycles	Burkitt lymphoma High Risk Arm Etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH-R) every 21 days for 6 cycles	Diffuse large B-cell lymphoma (DLBCL) high risk arm Etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH-R) every 21 days for 6 cycles
Overall Number of Participants Analyzed	15	98	53
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	100; (1 to 100)	82.1; (72.7 to 88.5)	71.0; (56.5 to 81.4)

2. Primary Outcome

Title	Percentage of Participants With Kaplan-Meier Curve Event Free Survival (EFS) Constructed With an 95% Confidence Interval
Description	EFS was determined from the date of enrolment in the study until the date of progression, last documentation of disease at or after the last treatment cycle, death, or last follow-up (whichever occurred first). Disease progression was measured by the International Workshop Criteria (IWC). Progression is a positive positron emission tomography (PET) finding corresponding to the computed tomography (CT) abnormality (new lesion, increasing size of previous lesion), or a negative PET and a CT abnormality (new lesion, increasing size of previous lesion) of < 1.5 cm (< 1.0 cm in the lungs). Kaplan-Meier curves were constructed with an 95% confidence interval.
Time Frame	At 4 years

Outcome Measure Data

Analysis Population Description

Those participants that were not analyzed for EFS were screen failures (did not have MYC+ Diffuse Large B-Cell Lymphoma (DLBCL).

Arm/Group Title	Group A - Low-risk Burkitt Lymphoma (BL)	Group B - High-Risk Burkitt Lymphoma (BL)	Group C - High-Risk Diffuse Large B Cell Lymphoma (DLBCL)
Arm/Group Description:	Burkitt lymphoma Low Risk Arm Etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH-R) every 21 days for 6 cycles	Burkitt lymphoma High Risk Arm Etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH-R) every 21 days for 6 cycles	Diffuse large B-cell lymphoma (DLBCL) high risk arm Etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH-R) every 21 days for 6 cycles
Overall Number of Participants Analyzed	15	98	53
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	100; (1 to 100)	82.1; (72.7 to 88.5)	71.0; (58.5 to 81.4)

3. Primary Outcome

Title	Percentage of Participants Kaplan-Meier Curve Overall Survival (OS) Constructed With an 95% Confidence Interval
Description	OS was calculated from the enrolment date until date of death or last follow-up using the Kaplan Meier. Kaplan-Meier curves were constructed with an 95% confidence interval.
Time Frame	At 4 years

Outcome Measure Data

Analysis Population Description

Those participants that were not analyzed for OS were screen failures (did not have MYC+ Diffuse Large B-Cell Lymphoma (DLBCL).

Arm/Group Title	Group A - Low-risk Burkitt Lymphoma (BL)	Group B - High-Risk Burkitt Lymphoma (BL)	Group C - High-Risk Diffuse Large B Cell Lymphoma (DLBCL)
Arm/Group Description:	Burkitt lymphoma Low Risk Arm Etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH-R) every 21 days for 6 cycles	Burkitt lymphoma High Risk Arm Etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH-R) every 21 days for 6 cycles	Diffuse large B-cell lymphoma (DLBCL) high risk arm Etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH-R) every 21 days for 6 cycles
Overall Number of Participants Analyzed	15	98	53
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	100; (1 to 100)	84.9; (75.8 to 90.8)	76.7; (62.6 to 86.1)

4. Secondary Outcome

Title	Kaplan-Meier Progression Free Survival (PFS) Constructed With an 95% Confidence Interval in Participants Who Underwent Fluorodeoxyglucose (FDG)-Positron Emission Tomography (PET) and/or Computed Tomography (CT) Scans After Cycle 2
Description	The predictive value of early FDG-PET/CT scans on PFS was assessed after cycle 2. PFS is the time interval from start of treatment to documented evidence of disease progression, assessed by the International Workshop Criteria (IWC). Progression is a positive positron emission tomography (PET) finding corresponding to the computed tomography (CT) abnormality (new lesion, increasing size of previous lesion), or a negative PET and a CT abnormality (new lesion, increasing size of previous lesion) of < 1.5 cm (< 1.0 cm in the lungs). Kaplan-Meier curves were constructed with an 95% confidence interval.
Time Frame	After 2 cycles of therapy and prior to cycle 3

Outcome Measure Data

Analysis Population Description

51/98 participants and 34/81 participants did not receive a PET scan.

Arm/Group Title	Group A - Low-risk Burkitt Lymphoma (BL)	Group B - High-Risk Burkitt Lymphoma (BL)	Group C - High-Risk Diffuse Large B Cell Lymphoma (DLBCL)
Arm/Group Description:	Burkitt lymphoma Low Risk Arm Etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH-R) every 21 days for 6 cycles	Burkitt lymphoma High Risk Arm Etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH-R) every 21 days for 6 cycles	Diffuse large B-cell lymphoma (DLBCL) high risk arm Etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH-R) every 21 days for 6 cycles
Overall Number of Participants Analyzed	15	51	34
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	100; (1 to 100)	90.0; (77.7 to 95.7)	78.7; (60.5 to 89.2)

5. Other Pre-specified Outcome

Title	Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0)
Description	Here is the number of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.
Time Frame	Date treatment consent signed to date off study, approximately 102 months and 25 days for Group A, 125 months and 28 days for Group B and 117 months and 29 days for group C.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Group A - Low-risk Burkitt Lymphoma (BL)	Group B - High-Risk Burkitt Lymphoma (BL)	Group C - High-Risk Diffuse Large B Cell Lymphoma (DLBCL)
Arm/Group Description:	Burkitt lymphoma Low Risk Arm Etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH-R) every 21 days for 6 cycles	Burkitt lymphoma High Risk Arm Etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH-R) every 21 days for 6 cycles	Diffuse large B-cell lymphoma (DLBCL) high risk arm Etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH-R) every 21 days for 6 cycles
Overall Number of Participants Analyzed	15	98	81
Measure Type: Count of Participants; Unit of Measure: Participants
	13 86.7%	87 88.8%	72 88.9%

Adverse Events

Time Frame	Date treatment consent signed to date off study, approximately 102 months and 25 days for Group A, 125 months and 28 days for Group B and 117 months and 29 days for group C.
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Group A - Low-risk Burkitt Lymphoma (BL)		Group B - High-Risk Burkitt Lymphoma (BL)		Group C - High-Risk Diffuse Large B Cell Lymphoma (DLBCL)
Arm/Group Description	Burkitt lymphoma Low Risk Arm Etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH-R) every 21 days for 6 cycles		Burkitt lymphoma High Risk Arm Etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH-R) every 21 days for 6 cycles		Diffuse large B-cell lymphoma (DLBCL) high risk arm Etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH-R) every 21 days for 6 cycles
All-Cause Mortality
	Group A - Low-risk Burkitt Lymphoma (BL)		Group B - High-Risk Burkitt Lymphoma (BL)		Group C - High-Risk Diffuse Large B Cell Lymphoma (DLBCL)
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	0/15 (0.00%)		16/98 (16.33%)		3/81 (3.70%)
Serious Adverse Events
	Group A - Low-risk Burkitt Lymphoma (BL)		Group B - High-Risk Burkitt Lymphoma (BL)		Group C - High-Risk Diffuse Large B Cell Lymphoma (DLBCL)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/15 (20.00%)		58/98 (59.18%)		33/81 (40.74%)
Blood and lymphatic system disorders
Anemia † 1	1/15 (6.67%)	2	12/98 (12.24%)	21	4/81 (4.94%)	5
Febrile neutropenia † 1	0/15 (0.00%)	0	27/98 (27.55%)	48	11/81 (13.58%)	16
Cardiac disorders
Atrial fibrillation † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	1/81 (1.23%)	1
Cardiac arrest † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	0/81 (0.00%)	0
Cardiac disorders - Other, hypotension † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	0/81 (0.00%)	0
Chest pain - cardiac † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	0/81 (0.00%)	0
Myocardial infarction † 1	0/15 (0.00%)	0	0/98 (0.00%)	0	1/81 (1.23%)	1
Restrictive cardiomyopathy † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	0/81 (0.00%)	0
Gastrointestinal disorders
Abdominal distension † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	0/81 (0.00%)	0
Abdominal pain † 1	0/15 (0.00%)	0	2/98 (2.04%)	3	1/81 (1.23%)	1
Colitis † 1	0/15 (0.00%)	0	2/98 (2.04%)	2	1/81 (1.23%)	1
Diarrhea † 1	0/15 (0.00%)	0	0/98 (0.00%)	0	2/81 (2.47%)	3
Gastric perforation † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	0/81 (0.00%)	0
Gastrointestinal disorders - Other, bleeding † 1	0/15 (0.00%)	0	2/98 (2.04%)	2	1/81 (1.23%)	1
Ileus † 1	0/15 (0.00%)	0	0/98 (0.00%)	0	1/81 (1.23%)	1
Jejunal perforation † 1	0/15 (0.00%)	0	0/98 (0.00%)	0	1/81 (1.23%)	1
Lower gastrointestinal hemorrhage † 1	0/15 (0.00%)	0	2/98 (2.04%)	2	1/81 (1.23%)	1
Mucositis oral † 1	0/15 (0.00%)	0	8/98 (8.16%)	11	0/81 (0.00%)	0
Nausea † 1	0/15 (0.00%)	0	2/98 (2.04%)	2	2/81 (2.47%)	3
Oral pain † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	0/81 (0.00%)	0
Pancreatitis † 1	0/15 (0.00%)	0	0/98 (0.00%)	0	1/81 (1.23%)	1
Small intestinal obstruction † 1	0/15 (0.00%)	0	1/98 (1.02%)	2	0/81 (0.00%)	0
Vomiting † 1	0/15 (0.00%)	0	3/98 (3.06%)	3	2/81 (2.47%)	3
Gastrointestinal disorders - Other, heme positive stool † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	0/81 (0.00%)	0
Gastrointestinal disorders - Other, odynohagia † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	0/81 (0.00%)	0
General disorders
Death NOS † 1	0/15 (0.00%)	0	10/98 (10.20%)	10	9/81 (11.11%)	9
Edema limbs † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	0/81 (0.00%)	0
Fatigue † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	0/81 (0.00%)	0
Fever † 1	0/15 (0.00%)	0	6/98 (6.12%)	7	1/81 (1.23%)	1
General disorders and administration site conditions - Other, specify † 1 [1]	0/15 (0.00%)	0	1/98 (1.02%)	1	0/81 (0.00%)	0
Infusion related reaction † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	0/81 (0.00%)	0
Multi-organ failure † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	2/81 (2.47%)	2
Pain † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	0/81 (0.00%)	0
Infections and infestations
Catheter related infection † 1	1/15 (6.67%)	1	0/98 (0.00%)	0	0/81 (0.00%)	0
Device related infection † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	0/81 (0.00%)	0
Infections and infestations - Other, cellulitis † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	0/81 (0.00%)	0
Lung infection † 1	0/15 (0.00%)	0	3/98 (3.06%)	3	1/81 (1.23%)	1
Phlebitis infective † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	0/81 (0.00%)	0
Sepsis † 1	0/15 (0.00%)	0	6/98 (6.12%)	6	4/81 (4.94%)	6
Sinusitis † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	0/81 (0.00%)	0
Skin infection † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	0/81 (0.00%)	0
Infections and infestations - Other, clostridium difficile † 1	1/15 (6.67%)	1	0/98 (0.00%)	0	0/81 (0.00%)	0
Infections and infestations - Other, influenza A/H1N1 † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	0/81 (0.00%)	0
Infections and infestations - Other, Infected Cholecystostomy tube in setting of neutropenia? † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	0/81 (0.00%)	0
Infections and infestations - Other, neutropenic fever † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	0/81 (0.00%)	0
Infections and infestations - Other, liver infection † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	0/81 (0.00%)	0
Injury, poisoning and procedural complications
Vascular access complication † 1	0/15 (0.00%)	0	2/98 (2.04%)	2	0/81 (0.00%)	0
Investigations
Alanine aminotransferase increased † 1	0/15 (0.00%)	0	0/98 (0.00%)	0	1/81 (1.23%)	1
Aspartate aminotransferase increased † 1	0/15 (0.00%)	0	0/98 (0.00%)	0	1/81 (1.23%)	1
Ejection fraction decreased † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	1/81 (1.23%)	1
Lymphocyte count decreased † 1	1/15 (6.67%)	1	7/98 (7.14%)	14	3/81 (3.70%)	7
Neutrophil count decreased † 1	1/15 (6.67%)	1	11/98 (11.22%)	26	5/81 (6.17%)	8
Platelet count decreased † 1	0/15 (0.00%)	0	6/98 (6.12%)	12	4/81 (4.94%)	6
White blood cell decreased † 1	0/15 (0.00%)	0	15/98 (15.31%)	38	5/81 (6.17%)	7
Metabolism and nutrition disorders
Dehydration † 1	0/15 (0.00%)	0	3/98 (3.06%)	3	2/81 (2.47%)	2
Hyperglycemia † 1	0/15 (0.00%)	0	2/98 (2.04%)	2	2/81 (2.47%)	2
Hypoalbuminemia † 1	0/15 (0.00%)	0	0/98 (0.00%)	0	2/81 (2.47%)	3
Hypocalcemia † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	0/81 (0.00%)	0
Hypokalemia † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	0/81 (0.00%)	0
Hyponatremia † 1	1/15 (6.67%)	1	3/98 (3.06%)	3	2/81 (2.47%)	2
Hypophosphatemia † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	0/81 (0.00%)	0
Tumor lysis syndrome † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	1/81 (1.23%)	1
Musculoskeletal and connective tissue disorders
Bone pain † 1	0/15 (0.00%)	0	0/98 (0.00%)	0	1/81 (1.23%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Myelodysplastic syndrome † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	0/81 (0.00%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify † 1 [2]	0/15 (0.00%)	0	1/98 (1.02%)	1	0/81 (0.00%)	0
Treatment related secondary malignancy † 1	0/15 (0.00%)	0	0/98 (0.00%)	0	1/81 (1.23%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify † 1 [3]	0/15 (0.00%)	0	1/98 (1.02%)	1	1/81 (1.23%)	1
Nervous system disorders
Cerebrospinal fluid leakage † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	0/81 (0.00%)	0
Dizziness † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	1/81 (1.23%)	1
Headache † 1	0/15 (0.00%)	0	0/98 (0.00%)	0	1/81 (1.23%)	1
Intracranial hemorrhage † 1	0/15 (0.00%)	0	2/98 (2.04%)	2	0/81 (0.00%)	0
Syncope † 1	0/15 (0.00%)	0	0/98 (0.00%)	0	4/81 (4.94%)	4
Vasovagal reaction † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	0/81 (0.00%)	0
Psychiatric disorders
Hallucinations † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	0/81 (0.00%)	0
Renal and urinary disorders
Acute kidney injury † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	3/81 (3.70%)	4
Hematuria † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	0/81 (0.00%)	0
Proteinuria † 1	0/15 (0.00%)	0	0/98 (0.00%)	0	1/81 (1.23%)	1
Renal and urinary disorders - Other, acute kidney injury † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	0/81 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Aspiration † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	0/81 (0.00%)	0
Bronchopulmonary hemorrhage † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	0/81 (0.00%)	0
Hypoxia † 1	0/15 (0.00%)	0	2/98 (2.04%)	2	0/81 (0.00%)	0
Pneumonitis † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	1/81 (1.23%)	1
Respiratory failure † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	3/81 (3.70%)	3
Respiratory, thoracic and mediastinal disorders - Other, specify † 1 [4]	0/15 (0.00%)	0	1/98 (1.02%)	1	0/81 (0.00%)	0
Skin and subcutaneous tissue disorders
Toxic epidermal necrolysis † 1	0/15 (0.00%)	0	0/98 (0.00%)	0	1/81 (1.23%)	1
Vascular disorders
Hematoma † 1	0/15 (0.00%)	0	0/98 (0.00%)	0	1/81 (1.23%)	1
Hypertension † 1	0/15 (0.00%)	0	0/98 (0.00%)	0	1/81 (1.23%)	1
Hypotension † 1	0/15 (0.00%)	0	4/98 (4.08%)	5	2/81 (2.47%)	2
Thromboembolic event † 1	0/15 (0.00%)	0	3/98 (3.06%)	3	1/81 (1.23%)	1
1 Term from vocabulary, CTCAE (4.0); † Indicates events were collected by systematic assessment; [1] Weakness, difficulty swallowing, esophagitis; [2] Cholangiocarcinoma of liver; [3] Progressive disease; [4] Pharyngeal pain
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Group A - Low-risk Burkitt Lymphoma (BL)		Group B - High-Risk Burkitt Lymphoma (BL)		Group C - High-Risk Diffuse Large B Cell Lymphoma (DLBCL)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	13/15 (86.67%)		88/98 (89.80%)		71/81 (87.65%)
Blood and lymphatic system disorders
Anemia † 1	6/15 (40.00%)	9	62/98 (63.27%)	216	53/81 (65.43%)	181
Blood and lymphatic system disorders - Other, DVT † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	0/81 (0.00%)	0
Febrile neutropenia † 1	1/15 (6.67%)	1	29/98 (29.59%)	42	22/81 (27.16%)	35
Leukocytosis † 1	0/15 (0.00%)	0	3/98 (3.06%)	3	2/81 (2.47%)	2
Blood and lymphatic system disorders - Other, leukopenia † 1	0/15 (0.00%)	0	2/98 (2.04%)	4	0/81 (0.00%)	0
Blood and lymphatic system disorders - Other, low ANC † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	0/81 (0.00%)	0
Blood and lymphatic system disorders - Other, low platelet count † 1	0/15 (0.00%)	0	2/98 (2.04%)	2	0/81 (0.00%)	0
Blood and lymphatic system disorders - Other, T bili † 1	0/15 (0.00%)	0	0/98 (0.00%)	0	2/81 (2.47%)	2
Blood and lymphatic system disorders - Other, thrombosis/embolism † 1	0/15 (0.00%)	0	0/98 (0.00%)	0	1/81 (1.23%)	1
Cardiac disorders
Acute coronary syndrome † 1	0/15 (0.00%)	0	0/98 (0.00%)	0	1/81 (1.23%)	1
Atrial fibrillation † 1	0/15 (0.00%)	0	5/98 (5.10%)	6	2/81 (2.47%)	2
Atrial flutter † 1	0/15 (0.00%)	0	0/98 (0.00%)	0	1/81 (1.23%)	1
Cardiac disorders - Other, 23% decreased EF † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	0/81 (0.00%)	0
Chest pain - cardiac † 1	1/15 (6.67%)	1	1/98 (1.02%)	1	0/81 (0.00%)	0
Palpitations † 1	0/15 (0.00%)	0	0/98 (0.00%)	0	1/81 (1.23%)	1
Sinus bradycardia † 1	1/15 (6.67%)	1	2/98 (2.04%)	2	0/81 (0.00%)	0
Sinus tachycardia † 1	0/15 (0.00%)	0	4/98 (4.08%)	4	4/81 (4.94%)	5
Supraventricular tachycardia † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	0/81 (0.00%)	0
Ear and labyrinth disorders
Ear pain † 1	0/15 (0.00%)	0	0/98 (0.00%)	0	2/81 (2.47%)	2
Tinnitus † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	1/81 (1.23%)	1
Vertigo † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	0/81 (0.00%)	0
Endocrine disorders
Adrenal insufficiency † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	0/81 (0.00%)	0
Eye disorders
Blurred vision † 1	0/15 (0.00%)	0	3/98 (3.06%)	3	2/81 (2.47%)	2
Eyelid function disorder † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	0/81 (0.00%)	0
Floaters † 1	0/15 (0.00%)	0	0/98 (0.00%)	0	1/81 (1.23%)	1
Photophobia † 1	0/15 (0.00%)	0	0/98 (0.00%)	0	1/81 (1.23%)	1
Retinal detachment † 1	0/15 (0.00%)	0	0/98 (0.00%)	0	1/81 (1.23%)	1
Watering eyes † 1	0/15 (0.00%)	0	0/98 (0.00%)	0	2/81 (2.47%)	2
Gastrointestinal disorders
Abdominal distension † 1	0/15 (0.00%)	0	3/98 (3.06%)	3	0/81 (0.00%)	0
Abdominal infection † 1	0/15 (0.00%)	0	2/98 (2.04%)	2	0/81 (0.00%)	0
Abdominal pain † 1	2/15 (13.33%)	2	8/98 (8.16%)	11	5/81 (6.17%)	5
Anal fistula † 1	0/15 (0.00%)	0	0/98 (0.00%)	0	1/81 (1.23%)	1
Ascites † 1	0/15 (0.00%)	0	0/98 (0.00%)	0	1/81 (1.23%)	1
Bloating † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	0/81 (0.00%)	0
Colitis † 1	0/15 (0.00%)	0	0/98 (0.00%)	0	1/81 (1.23%)	1
Constipation † 1	6/15 (40.00%)	6	20/98 (20.41%)	23	22/81 (27.16%)	37
Diarrhea † 1	0/15 (0.00%)	0	18/98 (18.37%)	20	17/81 (20.99%)	22
Dry mouth † 1	0/15 (0.00%)	0	0/98 (0.00%)	0	2/81 (2.47%)	2
Dyspepsia † 1	0/15 (0.00%)	0	2/98 (2.04%)	3	3/81 (3.70%)	3
Dysphagia † 1	0/15 (0.00%)	0	4/98 (4.08%)	4	2/81 (2.47%)	2
Enterocolitis † 1	0/15 (0.00%)	0	2/98 (2.04%)	2	0/81 (0.00%)	0
Esophageal hemorrhage † 1	0/15 (0.00%)	0	0/98 (0.00%)	0	1/81 (1.23%)	1
Esophagitis † 1	0/15 (0.00%)	0	2/98 (2.04%)	2	0/81 (0.00%)	0
Fecal incontinence † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	0/81 (0.00%)	0
Flatulence † 1	1/15 (6.67%)	1	0/98 (0.00%)	0	2/81 (2.47%)	2
Gastritis † 1	1/15 (6.67%)	1	1/98 (1.02%)	1	2/81 (2.47%)	2
Gastroesophageal reflux disease † 1	0/15 (0.00%)	0	2/98 (2.04%)	2	2/81 (2.47%)	2
Gastrointestinal disorders - Other, epigastric pain † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	0/81 (0.00%)	0
Hemorrhoids † 1	0/15 (0.00%)	0	3/98 (3.06%)	3	1/81 (1.23%)	2
Ileus † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	3/81 (3.70%)	4
Mucositis oral † 1	1/15 (6.67%)	1	23/98 (23.47%)	47	20/81 (24.69%)	31
Nausea † 1	1/15 (6.67%)	3	18/98 (18.37%)	25	11/81 (13.58%)	16
Oral hemorrhage † 1	1/15 (6.67%)	1	0/98 (0.00%)	0	0/81 (0.00%)	0
Oral pain † 1	1/15 (6.67%)	1	1/98 (1.02%)	1	1/81 (1.23%)	5
Rectal hemorrhage † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	1/81 (1.23%)	1
Stomach pain † 1	0/15 (0.00%)	0	0/98 (0.00%)	0	1/81 (1.23%)	1
Toothache † 1	1/15 (6.67%)	1	2/98 (2.04%)	2	0/81 (0.00%)	0
Typhlitis † 1	0/15 (0.00%)	0	2/98 (2.04%)	2	0/81 (0.00%)	0
Vomiting † 1	0/15 (0.00%)	0	9/98 (9.18%)	14	7/81 (8.64%)	8
General disorders
Chills † 1	1/15 (6.67%)	1	5/98 (5.10%)	6	2/81 (2.47%)	2
Death NOS † 1	0/15 (0.00%)	0	2/98 (2.04%)	2	1/81 (1.23%)	1
Edema limbs † 1	0/15 (0.00%)	0	3/98 (3.06%)	3	11/81 (13.58%)	12
Fatigue † 1	4/15 (26.67%)	7	22/98 (22.45%)	28	22/81 (27.16%)	35
Fever † 1	1/15 (6.67%)	1	13/98 (13.27%)	16	8/81 (9.88%)	10
Flu like symptoms † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	2/81 (2.47%)	2
Gait disturbance † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	0/81 (0.00%)	0
General disorders and administration site conditions - Other, cerebellar infarct † 1	0/15 (0.00%)	0	2/98 (2.04%)	3	0/81 (0.00%)	0
Infusion related reaction † 1	0/15 (0.00%)	0	2/98 (2.04%)	2	3/81 (3.70%)	3
Neck edema † 1	0/15 (0.00%)	0	2/98 (2.04%)	2	0/81 (0.00%)	0
Pain † 1	1/15 (6.67%)	1	10/98 (10.20%)	14	6/81 (7.41%)	7
General disorders and administration site conditions - Other, sacral pressure ulcer † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	0/81 (0.00%)	0
General disorders and administration site conditions - Other, thalmic infarct † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	0/81 (0.00%)	0
Hepatobiliary disorders
Hepatic failure † 1	0/15 (0.00%)	0	0/98 (0.00%)	0	1/81 (1.23%)	1
Immune system disorders
Allergic reaction † 1	0/15 (0.00%)	0	3/98 (3.06%)	3	2/81 (2.47%)	2
Infections and infestations
Anorectal infection † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	1/81 (1.23%)	1
Bladder infection † 1	0/15 (0.00%)	0	0/98 (0.00%)	0	1/81 (1.23%)	1
Bronchial infection † 1	0/15 (0.00%)	0	0/98 (0.00%)	0	1/81 (1.23%)	1
Catheter related infection † 1	0/15 (0.00%)	0	0/98 (0.00%)	0	1/81 (1.23%)	1
Enterocolitis infectious † 1	0/15 (0.00%)	0	2/98 (2.04%)	2	4/81 (4.94%)	4
Esophageal infection † 1	0/15 (0.00%)	0	0/98 (0.00%)	0	1/81 (1.23%)	1
Eye infection † 1	0/15 (0.00%)	0	0/98 (0.00%)	0	1/81 (1.23%)	1
Infections and infestations - Other, bacteremia † 1	1/15 (6.67%)	1	0/98 (0.00%)	0	0/81 (0.00%)	0
Lung infection † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	1/81 (1.23%)	1
Mucosal infection † 1	0/15 (0.00%)	0	8/98 (8.16%)	12	4/81 (4.94%)	5
Peritoneal infection † 1	0/15 (0.00%)	0	0/98 (0.00%)	0	1/81 (1.23%)	1
Rhinitis infective † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	0/81 (0.00%)	0
Sepsis † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	2/81 (2.47%)	2
Sinusitis † 1	0/15 (0.00%)	0	0/98 (0.00%)	0	1/81 (1.23%)	1
Skin infection † 1	0/15 (0.00%)	0	2/98 (2.04%)	2	0/81 (0.00%)	0
Upper respiratory infection † 1	1/15 (6.67%)	1	0/98 (0.00%)	0	1/81 (1.23%)	1
Urethral infection † 1	0/15 (0.00%)	0	0/98 (0.00%)	0	1/81 (1.23%)	1
Urinary tract infection † 1	0/15 (0.00%)	0	8/98 (8.16%)	9	8/81 (9.88%)	11
Wound infection † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	1/81 (1.23%)	1
Infections and infestations - Other, Blood † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	0/81 (0.00%)	0
Infections and infestations - Other, blood infection † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	0/81 (0.00%)	0
Infections and infestations - Other, blood, E. coli † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	0/81 (0.00%)	0
Infections and infestations - Other, bacteremia, Klebsiella infection † 1	0/15 (0.00%)	0	0/98 (0.00%)	0	1/81 (1.23%)	1
Infections and infestations - Other, candida oral infection † 1	0/15 (0.00%)	0	1/98 (1.02%)	2	0/81 (0.00%)	0
Infections and infestations - Other, clostridium difficile † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	0/81 (0.00%)	0
Infections and infestations - Other, CMV reactivation † 1	0/15 (0.00%)	0	0/98 (0.00%)	0	1/81 (1.23%)	1
Infections and infestations - Other, encephalitis, persistent † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	0/81 (0.00%)	0
Infections and infestations - Other, gastrointestinal tract † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	0/81 (0.00%)	0
Infections and infestations - Other, infection † 1	0/15 (0.00%)	0	0/98 (0.00%)	0	1/81 (1.23%)	1
Infections and infestations - Other, infection-oral † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	0/81 (0.00%)	0
Infections and infestations - Other, L posterior lung † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	0/81 (0.00%)	0
Infections and infestations - Other, left orbital cellulitis † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	0/81 (0.00%)	0
Infections and infestations - Other, MRSA † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	0/81 (0.00%)	0
Infections and infestations - Other, oral cavity † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	0/81 (0.00%)	0
Infections and infestations - Other, parasitic infection † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	0/81 (0.00%)	0
Infections and infestations - Other, PICC line infection † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	0/81 (0.00%)	0
Infections and infestations - Other, polymicrobial bacteremia † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	0/81 (0.00%)	0
Infections and infestations - Other, throat † 1	0/15 (0.00%)	0	0/98 (0.00%)	0	1/81 (1.23%)	1
Infections and infestations - Other, thrush † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	0/81 (0.00%)	0
Infections and infestations - Other, VRE † 1	0/15 (0.00%)	0	0/98 (0.00%)	0	1/81 (1.23%)	1
Infections and infestations - Other, VRE-blood stream † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	0/81 (0.00%)	0
Infections and infestations - Other, blood, candida glabrata † 1	0/15 (0.00%)	0	0/98 (0.00%)	0	1/81 (1.23%)	1
Infections and infestations - Other, herpes simplex oral ulcer † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	0/81 (0.00%)	0
Infections and infestations - Other, oral thrush † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	1/81 (1.23%)	1
Injury, poisoning and procedural complications
Bruising † 1	0/15 (0.00%)	0	0/98 (0.00%)	0	1/81 (1.23%)	1
Fall † 1	0/15 (0.00%)	0	2/98 (2.04%)	2	1/81 (1.23%)	1
Investigations
Activated partial thromboplastin time prolonged † 1	0/15 (0.00%)	0	0/98 (0.00%)	0	2/81 (2.47%)	2
Alanine aminotransferase increased † 1	2/15 (13.33%)	2	15/98 (15.31%)	23	7/81 (8.64%)	14
Alkaline phosphatase increased † 1	0/15 (0.00%)	0	7/98 (7.14%)	10	12/81 (14.81%)	21
Aspartate aminotransferase increased † 1	1/15 (6.67%)	1	13/98 (13.27%)	18	7/81 (8.64%)	12
Blood bilirubin increased † 1	2/15 (13.33%)	2	9/98 (9.18%)	13	5/81 (6.17%)	9
CD4 lymphocytes decreased † 1	0/15 (0.00%)	0	0/98 (0.00%)	0	1/81 (1.23%)	1
Cardiac troponin I increased † 1	0/15 (0.00%)	0	0/98 (0.00%)	0	1/81 (1.23%)	1
Cardiac troponin T increased † 1	0/15 (0.00%)	0	0/98 (0.00%)	0	1/81 (1.23%)	1
Creatinine increased † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	1/81 (1.23%)	1
Elevated LFT's † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	0/81 (0.00%)	0
Elevated bilirubin † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	0/81 (0.00%)	0
GGT increased † 1	0/15 (0.00%)	0	0/98 (0.00%)	0	1/81 (1.23%)	1
Investigations - Other, disease progression † 1	0/15 (0.00%)	0	0/98 (0.00%)	0	1/81 (1.23%)	1
Lipase increased † 1	0/15 (0.00%)	0	0/98 (0.00%)	0	1/81 (1.23%)	1
Lymphocyte count decreased † 1	5/15 (33.33%)	11	54/98 (55.10%)	277	49/81 (60.49%)	239
Lymphocyte count increased † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	3/81 (3.70%)	3
Neutrophil count decreased † 1	5/15 (33.33%)	6	55/98 (56.12%)	201	49/81 (60.49%)	178
Pancreatic enzymes decreased † 1	0/15 (0.00%)	0	0/98 (0.00%)	0	1/81 (1.23%)	1
Platelet count decreased † 1	3/15 (20.00%)	3	52/98 (53.06%)	161	43/81 (53.09%)	159
Urine output decreased † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	0/81 (0.00%)	0
Weight gain † 1	0/15 (0.00%)	0	3/98 (3.06%)	5	1/81 (1.23%)	1
Weight loss † 1	0/15 (0.00%)	0	2/98 (2.04%)	2	5/81 (6.17%)	8
White blood cell decreased † 1	7/15 (46.67%)	10	47/98 (47.96%)	212	52/81 (64.20%)	218
Investigations - Other, heartburn † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	0/81 (0.00%)	0
Investigations - Other, night sweats † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	0/81 (0.00%)	0
Investigations - Other, fluid overload † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	0/81 (0.00%)	0
Metabolism and nutrition disorders
Alkalosis † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	0/81 (0.00%)	0
Anorexia † 1	1/15 (6.67%)	1	9/98 (9.18%)	10	6/81 (7.41%)	7
Dehydration † 1	0/15 (0.00%)	0	7/98 (7.14%)	11	2/81 (2.47%)	3
Glucose intolerance † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	0/81 (0.00%)	0
Hypercalcemia † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	3/81 (3.70%)	3
Hyperglycemia † 1	0/15 (0.00%)	0	16/98 (16.33%)	42	15/81 (18.52%)	37
Hyperkalemia † 1	0/15 (0.00%)	0	3/98 (3.06%)	3	3/81 (3.70%)	3
Hypermagnesemia † 1	1/15 (6.67%)	1	2/98 (2.04%)	2	3/81 (3.70%)	4
Hypernatremia † 1	0/15 (0.00%)	0	4/98 (4.08%)	5	8/81 (9.88%)	17
Hypertriglyceridemia † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	0/81 (0.00%)	0
Hyperuricemia † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	2/81 (2.47%)	2
Hypoalbuminemia † 1	0/15 (0.00%)	0	18/98 (18.37%)	32	15/81 (18.52%)	27
Hypocalcemia † 1	0/15 (0.00%)	0	17/98 (17.35%)	32	17/81 (20.99%)	28
Hypoglycemia † 1	0/15 (0.00%)	0	4/98 (4.08%)	7	3/81 (3.70%)	3
Hypokalemia † 1	1/15 (6.67%)	1	21/98 (21.43%)	32	18/81 (22.22%)	36
Hypomagnesemia † 1	0/15 (0.00%)	0	7/98 (7.14%)	13	6/81 (7.41%)	16
Hyponatremia † 1	1/15 (6.67%)	1	14/98 (14.29%)	19	6/81 (7.41%)	8
Hypophosphatemia † 1	2/15 (13.33%)	2	22/98 (22.45%)	36	20/81 (24.69%)	29
Metabolism and nutrition disorders - Other, elevated LDH † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	0/81 (0.00%)	0
Tumor lysis syndrome † 1	0/15 (0.00%)	0	4/98 (4.08%)	4	0/81 (0.00%)	0
Metabolism and nutrition disorders - Other, malnutrition † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	0/81 (0.00%)	0
Musculoskeletal and connective tissue disorders
Arthralgia † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	0/81 (0.00%)	0
Back pain † 1	1/15 (6.67%)	1	7/98 (7.14%)	10	7/81 (8.64%)	7
Bone pain † 1	2/15 (13.33%)	3	9/98 (9.18%)	13	7/81 (8.64%)	10
Chest wall pain † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	0/81 (0.00%)	0
Flank pain † 1	0/15 (0.00%)	0	0/98 (0.00%)	0	1/81 (1.23%)	1
Generalized muscle weakness † 1	1/15 (6.67%)	1	4/98 (4.08%)	7	5/81 (6.17%)	6
Joint effusion † 1	0/15 (0.00%)	0	0/98 (0.00%)	0	1/81 (1.23%)	1
Muscle weakness lower limb † 1	0/15 (0.00%)	0	1/98 (1.02%)	2	0/81 (0.00%)	0
Muscle weakness trunk † 1	0/15 (0.00%)	0	0/98 (0.00%)	0	2/81 (2.47%)	2
Musculoskeletal and connective tissue disorder - Other, specify † 1 [1]	0/15 (0.00%)	0	1/98 (1.02%)	1	1/81 (1.23%)	1
Myalgia † 1	1/15 (6.67%)	1	0/98 (0.00%)	0	1/81 (1.23%)	2
Neck pain † 1	1/15 (6.67%)	1	3/98 (3.06%)	3	1/81 (1.23%)	1
Non-cardiac chest pain † 1	0/15 (0.00%)	0	2/98 (2.04%)	2	0/81 (0.00%)	0
Pain in extremity † 1	0/15 (0.00%)	0	2/98 (2.04%)	3	3/81 (3.70%)	4
Musculoskeletal and connective tissue disorder - Other, shin pain with numbness † 1	0/15 (0.00%)	0	0/98 (0.00%)	0	1/81 (1.23%)	1
Nervous system disorders
Cerebrospinal fluid leakage † 1	0/15 (0.00%)	0	2/98 (2.04%)	3	0/81 (0.00%)	0
Cognitive disturbance † 1	0/15 (0.00%)	0	1/98 (1.02%)	2	0/81 (0.00%)	0
Depressed level of consciousness † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	0/81 (0.00%)	0
Dizziness † 1	0/15 (0.00%)	0	7/98 (7.14%)	9	3/81 (3.70%)	5
Dysgeusia † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	5/81 (6.17%)	6
Dysphasia † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	0/81 (0.00%)	0
Facial nerve disorder † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	0/81 (0.00%)	0
Headache † 1	1/15 (6.67%)	2	25/98 (25.51%)	31	11/81 (13.58%)	13
Memory impairment † 1	0/15 (0.00%)	0	2/98 (2.04%)	5	1/81 (1.23%)	1
Movements involuntary † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	0/81 (0.00%)	0
Nervous system disorders - Other, numbness in left arm † 1	1/15 (6.67%)	3	0/98 (0.00%)	0	2/81 (2.47%)	6
Paresthesia † 1	0/15 (0.00%)	0	5/98 (5.10%)	5	3/81 (3.70%)	10
Peripheral motor neuropathy † 1	0/15 (0.00%)	0	8/98 (8.16%)	9	8/81 (9.88%)	9
Peripheral sensory neuropathy † 1	5/15 (33.33%)	5	26/98 (26.53%)	33	22/81 (27.16%)	25
Presyncope † 1	0/15 (0.00%)	0	2/98 (2.04%)	4	2/81 (2.47%)	2
Seizure † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	0/81 (0.00%)	0
Somnolence † 1	0/15 (0.00%)	0	0/98 (0.00%)	0	1/81 (1.23%)	1
Syncope † 1	0/15 (0.00%)	0	5/98 (5.10%)	7	2/81 (2.47%)	2
Tremor † 1	0/15 (0.00%)	0	2/98 (2.04%)	2	0/81 (0.00%)	0
Nervous system disorders - Other, neuropathy † 1	1/15 (6.67%)	1	0/98 (0.00%)	0	1/81 (1.23%)	5
Nervous system disorders - Other, neuropathy, upper bilateral extremities † 1	2/15 (13.33%)	2	0/98 (0.00%)	0	0/81 (0.00%)	0
Psychiatric disorders
Agitation † 1	0/15 (0.00%)	0	2/98 (2.04%)	2	1/81 (1.23%)	1
Anxiety † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	2/81 (2.47%)	2
Confusion † 1	0/15 (0.00%)	0	3/98 (3.06%)	3	2/81 (2.47%)	2
Delirium † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	1/81 (1.23%)	1
Delusions † 1	0/15 (0.00%)	0	0/98 (0.00%)	0	1/81 (1.23%)	1
Depression † 1	0/15 (0.00%)	0	3/98 (3.06%)	3	1/81 (1.23%)	1
Insomnia † 1	1/15 (6.67%)	1	10/98 (10.20%)	12	6/81 (7.41%)	6
Personality change † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	0/81 (0.00%)	0
Psychiatric disorders - Other, non verbal † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	0/81 (0.00%)	0
Renal and urinary disorders
Acute kidney injury † 1	0/15 (0.00%)	0	0/98 (0.00%)	0	2/81 (2.47%)	2
Hematuria † 1	0/15 (0.00%)	0	2/98 (2.04%)	2	0/81 (0.00%)	0
Renal and urinary disorders - Other, dysuria † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	0/81 (0.00%)	0
Urinary frequency † 1	0/15 (0.00%)	0	0/98 (0.00%)	0	2/81 (2.47%)	2
Urinary tract pain † 1	1/15 (6.67%)	1	1/98 (1.02%)	1	2/81 (2.47%)	2
Urinary urgency † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	0/81 (0.00%)	0
Reproductive system and breast disorders
Scrotal pain † 1	0/15 (0.00%)	0	0/98 (0.00%)	0	1/81 (1.23%)	1
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	2/81 (2.47%)	2
Aspiration † 1	0/15 (0.00%)	0	0/98 (0.00%)	0	3/81 (3.70%)	3
Cough † 1	0/15 (0.00%)	0	6/98 (6.12%)	6	1/81 (1.23%)	1
Dyspnea † 1	1/15 (6.67%)	1	8/98 (8.16%)	9	7/81 (8.64%)	9
Epistaxis † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	0/81 (0.00%)	0
Hiccups † 1	0/15 (0.00%)	0	3/98 (3.06%)	3	0/81 (0.00%)	0
Hoarseness † 1	0/15 (0.00%)	0	2/98 (2.04%)	2	1/81 (1.23%)	1
Hypoxia † 1	0/15 (0.00%)	0	0/98 (0.00%)	0	2/81 (2.47%)	2
Laryngeal inflammation † 1	0/15 (0.00%)	0	0/98 (0.00%)	0	1/81 (1.23%)	1
Laryngeal mucositis † 1	0/15 (0.00%)	0	2/98 (2.04%)	2	0/81 (0.00%)	0
Nasal congestion † 1	0/15 (0.00%)	0	0/98 (0.00%)	0	1/81 (1.23%)	1
Pharyngeal mucositis † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	1/81 (1.23%)	1
Pharyngolaryngeal pain † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	0/81 (0.00%)	0
Pleural effusion † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	2/81 (2.47%)	2
Pneumonitis † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	0/81 (0.00%)	0
Postnasal drip † 1	0/15 (0.00%)	0	0/98 (0.00%)	0	1/81 (1.23%)	1
Productive cough † 1	0/15 (0.00%)	0	0/98 (0.00%)	0	2/81 (2.47%)	2
Pulmonary edema † 1	0/15 (0.00%)	0	0/98 (0.00%)	0	1/81 (1.23%)	1
Respiratory failure † 1	0/15 (0.00%)	0	0/98 (0.00%)	0	2/81 (2.47%)	2
Sleep apnea † 1	1/15 (6.67%)	3	1/98 (1.02%)	1	0/81 (0.00%)	0
Sore throat † 1	0/15 (0.00%)	0	4/98 (4.08%)	5	1/81 (1.23%)	1
Tracheal fistula † 1	0/15 (0.00%)	0	0/98 (0.00%)	0	1/81 (1.23%)	1
Skin and subcutaneous tissue disorders
Alopecia † 1	4/15 (26.67%)	6	9/98 (9.18%)	14	6/81 (7.41%)	6
Dry skin † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	0/81 (0.00%)	0
Hyperhidrosis † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	0/81 (0.00%)	0
Nail discoloration † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	0/81 (0.00%)	0
Nail loss † 1	0/15 (0.00%)	0	2/98 (2.04%)	2	0/81 (0.00%)	0
Pain of skin † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	0/81 (0.00%)	0
Papulopustular rash † 1	0/15 (0.00%)	0	2/98 (2.04%)	2	0/81 (0.00%)	0
Pruritus † 1	0/15 (0.00%)	0	3/98 (3.06%)	3	1/81 (1.23%)	1
Rash acneiform † 1	0/15 (0.00%)	0	0/98 (0.00%)	0	3/81 (3.70%)	3
Rash maculo-papular † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	1/81 (1.23%)	1
Rash pustular † 1	0/15 (0.00%)	0	0/98 (0.00%)	0	1/81 (1.23%)	1
Skin and subcutaneous tissue disorders - Other, abdominal abscess † 1	2/15 (13.33%)	2	4/98 (4.08%)	5	1/81 (1.23%)	1
Skin hyperpigmentation † 1	0/15 (0.00%)	0	2/98 (2.04%)	2	0/81 (0.00%)	0
Skin ulceration † 1	0/15 (0.00%)	0	0/98 (0.00%)	0	1/81 (1.23%)	1
Urticaria † 1	0/15 (0.00%)	0	0/98 (0.00%)	0	2/81 (2.47%)	2
Skin and subcutaneous tissue disorders - Other, blister ball of R foot † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	0/81 (0.00%)	0
Skin and subcutaneous tissue disorders - Other, dermatitis † 1	0/15 (0.00%)	0	0/98 (0.00%)	0	1/81 (1.23%)	1
Skin and subcutaneous tissue disorders - Other, forehead itching † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	0/81 (0.00%)	0
Skin and subcutaneous tissue disorders - Other, skin darkening † 1	1/15 (6.67%)	1	0/98 (0.00%)	0	0/81 (0.00%)	0
Skin and subcutaneous tissue disorders - Other, vitiligo † 1	1/15 (6.67%)	1	0/98 (0.00%)	0	0/81 (0.00%)	0
Skin and subcutaneous tissue disorders - Other, pressure ulcer † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	0/81 (0.00%)	0
Skin and subcutaneous tissue disorders - Other, scalp wound † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	0/81 (0.00%)	0
Vascular disorders
Hematoma † 1	0/15 (0.00%)	0	3/98 (3.06%)	4	0/81 (0.00%)	0
Hot flashes † 1	0/15 (0.00%)	0	1/98 (1.02%)	1	0/81 (0.00%)	0
Hypertension † 1	1/15 (6.67%)	1	5/98 (5.10%)	9	6/81 (7.41%)	12
Hypotension † 1	0/15 (0.00%)	0	8/98 (8.16%)	9	6/81 (7.41%)	8
Superficial thrombophlebitis † 1	0/15 (0.00%)	0	2/98 (2.04%)	2	0/81 (0.00%)	0
Thromboembolic event † 1	0/15 (0.00%)	0	6/98 (6.12%)	6	5/81 (6.17%)	5
1 Term from vocabulary, CTCAE (4.0); † Indicates events were collected by systematic assessment; [1] PICC line-associated shoulder pain

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT 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.

Results Point of Contact

• Name/Title: Dr. Mark J. Roschewski
• Organization: National Cancer Institute
• Phone: 240-760-6183
• EMail: roschewskimj@nih.gov

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Roschewski M, Dunleavy K, Abramson JS, Powell BL, Link BK, Patel P, Bierman PJ, Jagadeesh D, Mitsuyasu RT, Peace D, Watson PR, Hanna WT, Melani C, Lucas AN, Steinberg SM, Pittaluga S, Jaffe ES, Friedberg JW, Kahl BS, Little RF, Bartlett NL, Fanale MA, Noy A, Wilson WH. Multicenter Study of Risk-Adapted Therapy With Dose-Adjusted EPOCH-R in Adults With Untreated Burkitt Lymphoma. J Clin Oncol. 2020 Aug 1;38(22):2519-2529. doi: 10.1200/JCO.20.00303. Epub 2020 May 26.

Dunleavy K, Fanale MA, Abramson JS, Noy A, Caimi PF, Pittaluga S, Parekh S, Lacasce A, Hayslip JW, Jagadeesh D, Nagpal S, Lechowicz MJ, Gaur R, Lucas A, Melani C, Roschewski M, Steinberg SM, Jaffe ES, Kahl B, Friedberg JW, Little RF, Bartlett NL, Wilson WH. Dose-adjusted EPOCH-R (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab) in untreated aggressive diffuse large B-cell lymphoma with MYC rearrangement: a prospective, multicentre, single-arm phase 2 study. Lancet Haematol. 2018 Dec;5(12):e609-e617. doi: 10.1016/S2352-3026(18)30177-7.

• Responsible Party: Mark Roschewski, M.D., National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT01092182
• Other Study ID Numbers: 100052; 10-C-0052
• First Submitted: March 23, 2010
• First Posted: March 24, 2010
• Results First Submitted: September 29, 2021
• Results First Posted: October 19, 2021
• Last Update Posted: November 9, 2022