PrE0401: Phase II Randomized Trial Comparing GA101 and Rituximab in Untreated Low Tumor Burden Indolent Non-Hodgkin's Lymphoma

• Sponsor: PrECOG, LLC. (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01889797
• Collaborator: Genentech, Inc. (Industry)
• Enrollment: 32
• Locations: 28
• Arms: 2
• Duration (Months): 32
• Patients Per Site: 1.1
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

Patients with previously untreated low tumor burden indolent Non-Hodgkin's Lymphoma (NHL) will receive either rituximab or GA101 weekly for 4 weeks followed by re-staging to determine response.

Rituximab, an anti-CD20 chimeric antibody, was approved by the United States Food and Drug Administration in 1998 for the treatment of patients with relapsed low-grade B-cell lymphomas. Clinically, four weekly doses of rituximab have proven to be well tolerated and effective in previously untreated as well as relapsed patients with low-grade lymphoma.

GA101 is an anti-CD20 humanized and glyco-engineered monoclonal antibody. GA101 has been shown to have increased antibody-dependent cellular cytotoxicity (ADCC) and direct cell-death induction compared to Rituximab. It is possible that GA101 may have greater efficacy than rituximab.

PrE0401 Sub-Study Evaluation of Corrected QT (QTc) Interval and Pharmacokinetic Parameters in Patients Participating in GA101 (Obinutuzumab)

Approximately twenty-five patients randomized to GA101 may participate in the sub-study. Electrocardiograms and blood samples will be obtained.

Condition or Disease	Intervention/Treatment	Phase
Indolent Non-Hodgkin's Lymphoma	Biological: Arm A: Rituximab; Biological: Arm B: GA101	Phase 2

Detailed Description

According to the American Cancer Society, it is estimated that approximately 70,800 individuals will be diagnosed with non-Hodgkin's lymphoma (NHL) and over 18,990 men and women will die of the disease in 2014. The survival rates for patients with indolent NHL remained unchanged from the 1950s through the early 1990s, but recent evidence suggests that outcomes are improving. Indolent NHL is a particular challenge because it is an incurable disease requiring multiple treatments; yet relatively long survivals elevate the importance of quality of life associated with treatment.

Agents such as rituximab are active in patients with a low burden of disease and result in high response rates and durable remissions for most patients. However, the optimal therapeutic approach to patients with low-grade lymphoma with a low disease burden is controversial as conventional chemotherapy also results in high rates of response. Regardless of whether patients receive immunotherapy, chemotherapy, or a combination thereof, they unfortunately exhibit a continuing pattern of disease relapse and the median survival for newly diagnosed patients is between 7-10 years.

Rituximab and GA101 both target the CD20 antigen. The CD20 antigen is located on the surface of normal and malignant B-cell lymphocytes. An attractive feature of this target is that CD20 is not on hematopoietic stem cells, nor is it expressed in any great extent on other normal body tissues.

Studies in vitro have shown that rituximab predominantly induces antibody dependent cellular cytotoxicity (ADCC), but also binds complement and directly induces apoptosis in lymphoma cells.

GA101 shows increased ADCC related to an improved binding of the GA101 to the different allotypes expressed by natural killer cells and monocytes. It also has increased direct cell-death related to an elbow hinge amino acid exchange and Type II binding of the CD20 epitope. The safety of GA101 in NHL so far appears to be similar to that observed with rituximab in patients with NHL, except for a higher incidence of infusion-related reactions.

Depletion of malignant B-cells using anti-CD20 monoclonal antibodies has an acceptable safety profile, particularly in patients with low-grade B-cell lymphomas with a low disease burden. To determine whether treatment with GA101 results in better outcomes than that seen with rituximab and to determine which anti-CD20 antibody to utilize in future studies, we will conduct a randomized Phase II trial of rituximab and GA101 in patients with previously untreated low-grade lymphoma. Patients will receive either rituximab or GA101 weekly for 4 weeks followed by re-staging. The endpoints of the study will be the Complete Response (CR), Overall Response Rate (ORR), time to next treatment, progression free survival (PFS), and safety of each treatment arm.

PrE0401 Sub-Study Evaluation of Corrected QT (QTc) Interval and Pharmacokinetic Parameters in Patients Participating in GA101 (Obinutuzumab)

Patients randomized to GA101 and who consent to the sub-study will have electrocardiograms obtained pre and post Week 1 and Week 4 to investigate the effect of GA101 on QTc interval. Pharmacokinetic blood samples will also be done to evaluate serum concentrations of GA101 at the same time-points.

Study Design

• Study Type: Interventional
• Actual Enrollment: 32 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Randomized Trial Comparing GA101 (Obinutuzumab) and Rituximab in Patients With Previously Untreated Low Tumor Burden Indolent Non-Hodgkin's Lymphoma
• Study Start Date: Dec 1, 2013
• Actual Primary Completion Date: Apr 1, 2016
• Actual Study Completion Date: Aug 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Arm A: Rituximab Rituximab 375 mg/m² IV weekly for 4 weeks.	Biological: Arm A: Rituximab; Rituximab 375 mg/m² IV x 4 weekly doses.; Other Names: IDEC-C2B8 Chimeric anti-CD20 monoclonal antibody Rituxan NSC# 687451
Experimental: Arm B: GA101 GA101 1,000 mg IV weekly for 4 weeks.	Biological: Arm B: GA101; GA101 1,000 mg (flat dose) IV x 4 weekly doses.; Other Names: Obinutuzumab RO5072759 huMAB<CD20>

Outcome Measures

Primary Outcome Measures

1. Complete Response (CR) Rate [Re-staging (week 12, 13 or 14) and during follow-up if physician feels patient is subsequently in CR for up to 4 years]

   Positron Emission Tomography (PET)-documented CR rates after induction therapy (weekly treatment x 4 weeks with GA101 or rituximab) Definitions for clinical response are modified from the Revised Response Criteria for Malignant Lymphoma (Cheson BD, et al. Revised Response Criteria for Malignant Lymphoma. J Clin Oncol 2007; 25(5): 579-86). Lymph node measurements were taken from CT, CT portion of the PET/CT, or MRI scans where applicable. CR is defined as complete disappearance of all evidence of disease; PR as a >50% decrease in the sum of the products of the maximal perpendicular diameters of measured lesions (SPD) and no new sites; SD as failure to attain CR/PR or PD; and PD as any new lesion >1.5cm in any axis or ≥50% increase in previously involved sites.

Secondary Outcome Measures

1. PET Response Rate [Re-staging (week 12, 13 or 14)]

   PET response rate [PET-documented CR + Partial Response (PR)] based on PET scan results. Patients with unevaluable disease were included in the denominator.

2. Overall Response Rate [Baseline and Re-staging (week 12, 13 or 14)]

   Overall response rate (CR + PR by Cheson criteria) at re-staging (including bone marrow biopsy if CR suspected) by PET and Neck, Chest, Abdomen and Pelvic Computed Tomography (CT) scan. Patients with unevaluable disease were included in the denominator.

3. Progression Free Survival (PFS) [Percent of participants alive and progression-free at 1 year]

   CT scan every 3 months for 2 years, then every 6 months until progression. Compare PFS in each treatment arm. Progressive disease (PD) was defined using Cheson criteria as described in the Primary Outcome section above. Progression-free survival (PFS) was defined as the time from start of treatment to the documentation of PD or death, whichever occurs first. Patients alive and without PD were censored at the date of last disease assessment.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

Registration: Patients having both diffuse and follicular architectural elements will be considered eligible if the histology is predominantly follicular (≥ 50% of the cross-sectional area), and there is no evidence of transformation to a large cell histology.

• Biopsy-proven diagnosis of Grade 1 or 2 follicular non-Hodgkin's lymphoma with no evidence of transformation to large cell histology.

• Meet criteria for Low Tumor Burden:

• No nodal or extra nodal mass ≥ 7 centimeter (cm)

• <3 nodal masses >3 cm in diameter

• No systemic symptoms or B symptoms

• No splenomegaly >16 cm by CT scan

• No risk of compression of a vital organ.

• No leukemic phase with >5000/mm³ circulating lymphocytes.

• No cytopenias defined as:

• Platelets <100,000/mm³

• Hemoglobin (Hgb) <10 g/dL

• Absolute Neutrophil Count (ANC) <1500/mm³

• Must have Stage III or Stage IV disease.

• Baseline measurements/evaluations obtained within 6 weeks of registration. Patient must have at least one objective measurable disease parameter.

• Age ≥ 18 years.

• Eastern Oncology Cooperative Group Performance Status 0-1.

• Must not have received investigational agents within 30 days of registration.

• Signed Institutional Review Board (IRB)-approved informed consent.

• Willing to provide blood samples for research purposes.

• Women must not be pregnant or breastfeeding.

• Women of childbearing potential and sexually active males must use an accepted and effective method of contraception.

• No prior chemotherapy, radiotherapy or immunotherapy for lymphoma.

• No prior treatment with cytotoxic drugs or rituximab for a previous cancer or another condition (e.g. rheumatoid arthritis) or prior use of an anti-CD20 antibody.

• No prior use of any monoclonal antibody within 3 months of randomization.

• No history of severe allergic/anaphylactic reactions to humanized/murine monoclonal antibodies or known sensitivity/allergy to murine products.

• No history of prior malignancy except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the patient has been disease-free for at least 2 years and did not require treatment with cytotoxic drugs or rituximab.

• No major surgery within 4 weeks prior to randomization, other than for diagnosis.

• Must be Human Immunodeficiency Virus (HIV) negative.

• Have adequate organ function without growth factor and/or transfusion support within ≤ 2 weeks prior to registration:

• ANC ≥ 1500/mm³

• Hgb ≥ 10 g/dL

• Platelets ≥ 100,000/mm³

• Serum Creatinine ≤ 2x Upper Limit Normal (ULN)

• Total Bilirubin ≤ 2x ULN

• AST (aspartate aminotransferase)/ALT (alanine aminotransferase) ≤ 5x ULN

• PTT (Partial Thromboplastin Time) or aPTT (activated Partial Thromboplastin Time)

1.5x the ULN in the absence of a lupus anticoagulant

• INR (International Normalized Ratio) >1.5x the ULN in the absence of therapeutic anticoagulation

• No active, uncontrolled infections (afebrile for ≥ 48 hours off antibiotics).

• Must not receive immunization with attenuated live vaccines within 28 days prior to registration or during the study period.

• Must be tested for hepatitis B surface antigen (HBsAg) and total hepatitis B core antibody (anti-HBc) within 2 weeks of registration. Patients who are chronic carriers of HBsAg and anti-HBc are excluded.

• Must be tested for hepatitis C antibody within 2 week of registration. If this test is positive, patients are excluded unless a hepatitis C virus ribonucleic acid (HCV RNA) is negative.

• No evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results, including significant cardiovascular disease (i.e., severe arrhythmia, myocardial infarction within the previous 6 months, unstable arrhythmias, or unstable angina) or pulmonary disease.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of South Alabama	Mobile	Alabama	United States	36604
2	Marin Cancer Care	Greenbrae	California	United States	94904
3	St. Joseph's/Candler Health System	Savannah	Georgia	United States	31405
4	Decatur Memorial Hospital	Decatur	Illinois	United States	62526
5	Carle Cancer Center	Urbana	Illinois	United States	61801
6	Indiana University	Indianapolis	Indiana	United States	46202
7	Siouxland Hematology Oncology Associates	Sioux City	Iowa	United States	51101
8	Ochsner Cancer Institute	New Orleans	Louisiana	United States	70121
9	Greater Baltimore Medical Center	Baltimore	Maryland	United States	21204
10	Tufts Medical Center	Boston	Massachusetts	United States	02111
11	St. Joseph Mercy Health System	Ann Arbor	Michigan	United States	48106
12	Mayo Clinic	Rochester	Minnesota	United States	55905
13	Metro MN CCOP	St. Louis Park	Minnesota	United States	55416
14	Missouri Valley Cancer Consortium	Omaha	Nebraska	United States	68106
15	Montefiore Medical Center	Bronx	New York	United States	10467
16	Aultman Hospital	Canton	Ohio	United States	44710
17	University Hospitals Case Medical Center	Cleveland	Ohio	United States	44106
18	Toledo Community Oncology Program	Toledo	Ohio	United States	43617
19	Geisinger Medical Center	Danville	Pennsylvania	United States	17822
20	Fox Chase Cancer Center	Philadelphia	Pennsylvania	United States	19111
21	Reading Hospital	West Reading	Pennsylvania	United States	19611
22	Susquehanna Health Cancer Center	Williamsport	Pennsylvania	United States	17701
23	University of Virginia	Charlottesburg	Virginia	United States	22908
24	Charleston Area Medical Center (CAMC)	Charleston	West Virginia	United States	25304
25	Gundersen Health System	La Crosse	Wisconsin	United States	54601
26	Dean Clinic	Madison	Wisconsin	United States	53717
27	ProHealth Care, Inc.	Waukesha	Wisconsin	United States	53188
28	Aurora Health Care	Wauwatosa	Wisconsin	United States	53266

Sponsors and Collaborators

• PrECOG, LLC.
• Genentech, Inc.

Investigators

• Study Chair: Stephen Ansell, MD, Mayo Clinic in Minnesota

Study Documents (Full-Text)

None provided.

More Information

Publications

• Beers SA, Chan CH, French RR, Cragg MS, Glennie MJ. CD20 as a target for therapeutic type I and II monoclonal antibodies. Semin Hematol. 2010 Apr;47(2):107-14. doi: 10.1053/j.seminhematol.2010.01.001. Review.
• Hainsworth JD, Litchy S, Burris HA 3rd, Scullin DC Jr, Corso SW, Yardley DA, Morrissey L, Greco FA. Rituximab as first-line and maintenance therapy for patients with indolent non-hodgkin's lymphoma. J Clin Oncol. 2002 Oct 15;20(20):4261-7.
• Mössner E, Brünker P, Moser S, Püntener U, Schmidt C, Herter S, Grau R, Gerdes C, Nopora A, van Puijenbroek E, Ferrara C, Sondermann P, Jäger C, Strein P, Fertig G, Friess T, Schüll C, Bauer S, Dal Porto J, Del Nagro C, Dabbagh K, Dyer MJ, Poppema S, Klein C, Umaña P. Increasing the efficacy of CD20 antibody therapy through the engineering of a new type II anti-CD20 antibody with enhanced direct and immune effector cell-mediated B-cell cytotoxicity. Blood. 2010 Jun 3;115(22):4393-402. doi: 10.1182/blood-2009-06-225979. Epub 2010 Mar 1.
• Salles GA, et al. Efficacy and Safety of Obinutuzumab (GA101) Monotherapy in Relapsed/Refractory Indolent Non-Hodgkin's Lymphoma: Results from a Phase I/II Study (BO20999) American Society of Hematology Annual meeting 2011 Abstract 268.
• Sehn LH, Goy A, Offner FC, Martinelli G, Caballero MD, Gadeberg O, Baetz T, Zelenetz AD, Gaidano G, Fayad LE, Buckstein R, Friedberg JW, Crump M, Jaksic B, Zinzani PL, Padmanabhan Iyer S, Sahin D, Chai A, Fingerle-Rowson G, Press OW. Randomized Phase II Trial Comparing Obinutuzumab (GA101) With Rituximab in Patients With Relapsed CD20+ Indolent B-Cell Non-Hodgkin Lymphoma: Final Analysis of the GAUSS Study. J Clin Oncol. 2015 Oct 20;33(30):3467-74. doi: 10.1200/JCO.2014.59.2139. Epub 2015 Aug 17.

• Responsible Party: PrECOG, LLC.
• ClinicalTrials.gov Identifier: NCT01889797
• Other Study ID Numbers: PrE0401; BO25454
• First Posted: Jun 28, 2013
• Last Update Posted: May 5, 2017
• Last Verified: Mar 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by PrECOG, LLC.: Untreated Non-Hodgkin's Lymphoma; Low Tumor Burden Non-Hodgkin's Lymphoma; NHL; Indolent; Rituximab; Rituxan; GA101; Obinutuzumab
• Additional relevant MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin; Rituximab; Obinutuzumab

Study Results

Participant Flow

Arm/Group Title	Arm A: Rituximab	Arm B: GA101
Arm/Group Description	Rituximab 375 mg/m² IV weekly for 4 weeks. Arm A: Rituximab: Rituximab 375 mg/m² IV x 4 weekly doses.	GA101 1,000 mg IV weekly for 4 weeks. Arm B: GA101: GA101 1,000 mg (flat dose) IV x 4 weekly doses.
Period Title: Overall Study
STARTED	16	16
COMPLETED	16	16
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Arm A: Rituximab	Arm B: GA101	Total
Arm/Group Description	Rituximab 375 mg/m² IV weekly for 4 weeks. Arm A: Rituximab: Rituximab 375 mg/m² IV x 4 weekly doses.	GA101 1,000 mg IV weekly for 4 weeks. Arm B: GA101: GA101 1,000 mg (flat dose) IV x 4 weekly doses.	Total of all reporting groups
Overall Participants	16	16	32
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	52	59	56
Sex: Female, Male (Count of Participants)
Female	10 62.5%	5 31.3%	15 46.9%
Male	6 37.5%	11 68.8%	17 53.1%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	16 100%	16 100%	32 100%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	1 6.3%	0 0%	1 3.1%
White	15 93.8%	16 100%	31 96.9%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	16 100%	16 100%	32 100%
ECOG Performance Status (participants) [Number]
PS 0	12 75%	12 75%	24 75%
PS 1	4 25%	4 25%	8 25%
Modified Ann Arbor Staging (participants) [Number]
Stage III (1)	1 6.3%	5 31.3%	6 18.8%
Stage III (2)	5 31.3%	4 25%	9 28.1%
Stage IV	10 62.5%	7 43.8%	17 53.1%
Primary Tumor Type (participants) [Number]
Grade 1 Follicular NHL	10 62.5%	13 81.3%	23 71.9%
Grade 2 Follicular NHL	4 25%	3 18.8%	7 21.9%
Other	2 12.5%	0 0%	2 6.3%

Outcome Measures

1. Primary Outcome

Title	Complete Response (CR) Rate
Description	Positron Emission Tomography (PET)-documented CR rates after induction therapy (weekly treatment x 4 weeks with GA101 or rituximab) Definitions for clinical response are modified from the Revised Response Criteria for Malignant Lymphoma (Cheson BD, et al. Revised Response Criteria for Malignant Lymphoma. J Clin Oncol 2007; 25(5): 579-86). Lymph node measurements were taken from CT, CT portion of the PET/CT, or MRI scans where applicable. CR is defined as complete disappearance of all evidence of disease; PR as a >50% decrease in the sum of the products of the maximal perpendicular diameters of measured lesions (SPD) and no new sites; SD as failure to attain CR/PR or PD; and PD as any new lesion >1.5cm in any axis or ≥50% increase in previously involved sites.
Time Frame	Re-staging (week 12, 13 or 14) and during follow-up if physician feels patient is subsequently in CR for up to 4 years

Outcome Measure Data

Analysis Population Description

All participants were included in the analysis

Arm/Group Title	Arm A: Rituximab	Arm B: GA101
Arm/Group Description	Rituximab 375 mg/m² IV weekly for 4 weeks. Arm A: Rituximab: Rituximab 375 mg/m² IV x 4 weekly doses.	GA101 1,000 mg IV weekly for 4 weeks. Arm B: GA101: GA101 1,000 mg (flat dose) IV x 4 weekly doses.
Measure Participants	16	16
Number (80% Confidence Interval) [percentage of participants]	37.5 234.4%	56.2 351.3%

2. Secondary Outcome

Title	PET Response Rate
Description	PET response rate [PET-documented CR + Partial Response (PR)] based on PET scan results. Patients with unevaluable disease were included in the denominator.
Time Frame	Re-staging (week 12, 13 or 14)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm A: Rituximab	Arm B: GA101
Arm/Group Description	Rituximab 375 mg/m² IV weekly for 4 weeks. Arm A: Rituximab: Rituximab 375 mg/m² IV x 4 weekly doses.	GA101 1,000 mg IV weekly for 4 weeks. Arm B: GA101: GA101 1,000 mg (flat dose) IV x 4 weekly doses.
Measure Participants	16	16
Complete Response	6 37.5%	9 56.3%
Partial Response	5 31.3%	5 31.3%
Stable Disease	3 18.8%	2 12.5%
Progressive Disease	2 12.5%	0 0%

3. Secondary Outcome

Title	Overall Response Rate
Description	Overall response rate (CR + PR by Cheson criteria) at re-staging (including bone marrow biopsy if CR suspected) by PET and Neck, Chest, Abdomen and Pelvic Computed Tomography (CT) scan. Patients with unevaluable disease were included in the denominator.
Time Frame	Baseline and Re-staging (week 12, 13 or 14)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm A: Rituximab	Arm B: GA101
Arm/Group Description	Rituximab 375 mg/m² IV weekly for 4 weeks. Arm A: Rituximab: Rituximab 375 mg/m² IV x 4 weekly doses.	GA101 1,000 mg IV weekly for 4 weeks. Arm B: GA101: GA101 1,000 mg (flat dose) IV x 4 weekly doses.
Measure Participants	16	16
Number (80% Confidence Interval) [percentage of participants]	68.8 430%	87.5 546.9%

4. Secondary Outcome

Title	Progression Free Survival (PFS)
Description	CT scan every 3 months for 2 years, then every 6 months until progression. Compare PFS in each treatment arm. Progressive disease (PD) was defined using Cheson criteria as described in the Primary Outcome section above. Progression-free survival (PFS) was defined as the time from start of treatment to the documentation of PD or death, whichever occurs first. Patients alive and without PD were censored at the date of last disease assessment.
Time Frame	Percent of participants alive and progression-free at 1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm A: Rituximab	Arm B: GA101
Arm/Group Description	Rituximab 375 mg/m² IV weekly for 4 weeks. Arm A: Rituximab: Rituximab 375 mg/m² IV x 4 weekly doses.	GA101 1,000 mg IV weekly for 4 weeks. Arm B: GA101: GA101 1,000 mg (flat dose) IV x 4 weekly doses.
Measure Participants	16	16
Number (80% Confidence Interval) [percentage of participants]	68.8 430%	87.5 546.9%

Adverse Events

Adverse Event Reporting Description	Adverse events were assessed weekly, prior to and during administration of study drug.
Arm/Group Title	Arm A: Rituximab		Arm B: GA101
Arm/Group Description	Rituximab 375 mg/m² IV weekly for 4 weeks. Arm A: Rituximab: Rituximab 375 mg/m² IV x 4 weekly doses.		GA101 1,000 mg IV weekly for 4 weeks. Arm B: GA101: GA101 1,000 mg (flat dose) IV x 4 weekly doses.
All Cause Mortality
	Arm A: Rituximab		Arm B: GA101
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Arm A: Rituximab		Arm B: GA101
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/16 (0%)		2/16 (12.5%)
Cardiac disorders
Hypotension	0/16 (0%)		1/16 (6.3%)
General disorders
Infusion Related Reaction	0/16 (0%)		1/16 (6.3%)
Vascular disorders
Flushing	0/16 (0%)		1/16 (6.3%)
Other (Not Including Serious) Adverse Events
	Arm A: Rituximab		Arm B: GA101
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/16 (68.8%)		15/16 (93.8%)
Blood and lymphatic system disorders
Anemia	1/16 (6.3%)		0/16 (0%)
Eye disorders
Eye Disorder	0/16 (0%)		1/16 (6.3%)
Blurred Vision	0/16 (0%)		1/16 (6.3%)
Gastrointestinal disorders
Constipation	0/16 (0%)		1/16 (6.3%)
Diarrhea	1/16 (6.3%)		2/16 (12.5%)
Dysgeusia	0/16 (0%)		1/16 (6.3%)
Dyspepsia	0/16 (0%)		1/16 (6.3%)
Nausea	4/16 (25%)		3/16 (18.8%)
General disorders
Chills	1/16 (6.3%)		1/16 (6.3%)
Edema	1/16 (6.3%)		0/16 (0%)
Infusion Site Extravasation	1/16 (6.3%)		1/16 (6.3%)
Fatigue	3/16 (18.8%)		8/16 (50%)
Flu Like Symptoms	0/16 (0%)		1/16 (6.3%)
Infusion Related Reaction	5/16 (31.3%)		6/16 (37.5%)
Non-cardiac Chest Pain	0/16 (0%)		1/16 (6.3%)
Fever	0/16 (0%)		1/16 (6.3%)
Immune system disorders
Cytokine Release Syndrome	0/16 (0%)		2/16 (12.5%)
Dermatitis Allergic	1/16 (6.3%)		0/16 (0%)
Investigations
Alanine Aminotransferase Increased	1/16 (6.3%)		0/16 (0%)
Alkaline Phosphatase Increased	1/16 (6.3%)		0/16 (0%)
Lymphocyte Count Decreased	0/16 (0%)		1/16 (6.3%)
Neutrophil Count Decreased	1/16 (6.3%)		0/16 (0%)
Platelet Count Decreased	0/16 (0%)		2/16 (12.5%)
Metabolism and nutrition disorders
Decreased Appetite	1/16 (6.3%)		2/16 (12.5%)
Hyperglycemia	1/16 (6.3%)		0/16 (0%)
Hyperuricemia	0/16 (0%)		1/16 (6.3%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/16 (0%)		1/16 (6.3%)
Arthritis	1/16 (6.3%)		1/16 (6.3%)
Asthenia	0/16 (0%)		3/16 (18.8%)
Back Pain	0/16 (0%)		1/16 (6.3%)
Myalgia	2/16 (12.5%)		3/16 (18.8%)
Pain in Extremity	0/16 (0%)		1/16 (6.3%)
Nervous system disorders
Anxiety	1/16 (6.3%)		1/16 (6.3%)
Dizziness	0/16 (0%)		2/16 (12.5%)
Headache	1/16 (6.3%)		3/16 (18.8%)
Peripheral Motor Neuropathy	1/16 (6.3%)		0/16 (0%)
Tremor	1/16 (6.3%)		0/16 (0%)
Psychiatric disorders
Confusional State	0/16 (0%)		1/16 (6.3%)
Insomnia	0/16 (0%)		1/16 (6.3%)
Respiratory, thoracic and mediastinal disorders
Cough	1/16 (6.3%)		0/16 (0%)
Dyspnea	1/16 (6.3%)		0/16 (0%)
Sore Throat	0/16 (0%)		1/16 (6.3%)
Skin and subcutaneous tissue disorders
Hyperhidrosis	1/16 (6.3%)		1/16 (6.3%)
Rash	0/16 (0%)		1/16 (6.3%)
Vascular disorders
Hot Flashes	0/16 (0%)		1/16 (6.3%)
Hypertension	1/16 (6.3%)		0/16 (0%)
Hypotension	2/16 (12.5%)		0/16 (0%)

Limitations/Caveats

The study closed early due to slow accrual.

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.