ATLL: EPOCH Chemotherapy and Bortezomib for Associated T-Cell Leukemia Lymphoma

• Sponsor: Washington University School of Medicine (Other)
• Overall Status: Completed
• CT.gov ID: NCT01000285
• Collaborator: (none)
• Enrollment: 18
• Locations: 6
• Arm: 1
• Duration (Months): 67
• Patients Per Site: 3
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

The rationale of the current study is to explore the use of combination chemotherapy together with antiretroviral agents in order to determine the efficacy and toxicity of this approach, while also examining markers of virus replication and expression, and tumor cell proliferation to gain understanding of the biological basis of this malignancy and to identify predictors of response.

Condition or Disease	Intervention/Treatment	Phase
Leukemia-Lymphoma, Adult T-Cell	Drug: Bortezomib; Drug: Etoposide; Drug: Vincristine; Drug: Doxorubicin; Drug: Prednisone; Drug: Cyclophosphamide; Drug: Raltegravir	Phase 1/Phase 2

Detailed Description

Primary Endpoint:

• To determine the tolerability and efficacy (response rate) of dose adjusted bortezomib-EPOCH (DA B-EPOCH) chemotherapy combined with Raltegravir in patients with HTLV-1 associated leukemia/lymphoma (ATLL).

Secondary Endpoints:

• To evaluate the effects of DA B-EPOCH chemotherapy combined with Raltegravir on HTLV-1 DNA and RNA load, HTLV-1 integrase gene sequence, and HTLV-1 integration sites. To determine if relapsed or progressive disease is a result of renewed virus replication.

• To evaluate the relation of NFκB gene expression profile on response to DA B-EPOCH chemotherapy combined with Raltegravir.

Study Design

• Study Type: Interventional
• Actual Enrollment: 18 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase I/II Trial of Dose-Adjusted EPOCH Chemotherapy With Bortezomib Combined With Integrase Inhibitor Therapy for HTLV-1 Associated T-Cell Leukemia Lymphoma
• Study Start Date: Sep 1, 2010
• Actual Primary Completion Date: May 1, 2014
• Actual Study Completion Date: Apr 1, 2016

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Arm 1 Bortezomib 1.0 mg/m2 intravenous (IV) Days 1-4 Etoposide 50 mg/m2/d 96 hour continuous intravenous infusion (CIVI) on Days 1-4 Vincristine 0.4 mg/m2/d 96 hour CIVI on Days 1-4 Doxorubicin 10 mg/m2/d 96 hour CIVI on Days 1-4 Prednisone 60 mg/m2/d PO on Days 1-5 Cyclophosphamide 375 mg/m2 IV on Day 5 Raltegravir 400 mg PO twice per day (BID) every day starting with cycle 2 therapy for the entire duration of the cycle. Cycles will be repeated every 21-28 days for 2 cycles beyond best response, or a maximum of 6 cycles.

Drug: Bortezomib; Other Names: Velcade® ; Drug: Etoposide; Other Names: Toposar®, VePesid®, Etopophos® ; Drug: Vincristine; Other Names: Oncovin ®, Vincasar Pfs ® ; Drug: Doxorubicin; Other Names: Adriamycin ®, Rubex ® ; Drug: Prednisone; Other Names: Deltasone®, Liquid Pred®, Meticorten®, Orasone® ; Drug: Cyclophosphamide; Other Names: Cytoxan ®, Neosar ® ; Drug: Raltegravir; Other Names: Isentress®

Outcome Measures

Primary Outcome Measures

1. Tolerability of Treatment as Measured by Number of Participants With Grade 3 or Higher Adverse Events [Up to 30 days after completion of treatment]

   The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized for all toxicity reporting.

2. Efficacy of Treatment as Measured by Best Overall Response [Up to 4 years following completion of therapy]

   -The response definitions used for this study are the 2007 Cheson criteria.

Secondary Outcome Measures

1. Time to Progression [Up to 4 years following completion of therapy]

   -The progression definitions used for this study are from the 2007 Cheson criteria.

2. Effects of on HTLV-1 DNA After Treatment as Measured by Proviral Loads [6 months]

3. Relation of NFκB Gene Expression Profile on Response [6 months]

   Standard error represents the standard error of the fold expression of protein coding transcripts for each gene indicated.

4. Effects of HTLV-1 RNA Load After Treatment as Measured by Hbz Messenger RNA [6 months]

5. Effects of HTLV-1 Integrase Gene Sequence After Treatment as Measured by Nucleotide Divergence [6 months]

6. Effects of HTLV-1 Integration Sites After Treatment [6 months]

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Histologically or cytologically documented ATLL. Patients with previously untreated or treated ATLL are eligible.

• Tumors must be CD3 positive (>50% cells express CD3).

• Documented HTLV-1 infection: documentation may be serologic assay (ELISA, Western blot) Confirmation of HTLV-1 rather than HTLV-2 by differential Western blot (e.g. Genelabs Diagnostics HTLV Blot 2.4) or PCR is desirable but his result is not required prior to trial enrollment.

• Measurable disease must be present. These nodes or masses should be selected according to all of the following: they should be clearly measurable in at least two perpendicular dimensions; if possible they should be from disparate regions of the body; and they should include mediastinal and retroperitoneal areas of disease whenever these sites are involved.For patients with acute (leukemic) form of ATLL, measureable disease can be derived from CD4+ lymphocyte flow data on the peripheral blood and/or bone marrow.

• All stages are eligible.

• Adequate hematologic function within 14 days before enrollment: ANC>1000 cells/mm3, platelet count>75,000 cells/mm3 unless cytopenias are secondary to ATLL. All patients must be off hematologic growth factors for at least 24 hrs.

• Adequate hepatic function, transaminase <3 times the upper limit of normal unless due to to Gilbert's disease or hepatic involvement by tumor; total bilirubin ≤1.5 times the upper limit of normal

• Creatinine<2.0 unless due to lymphoma.

• Karnofsky Performance Status (KPS) at least 50

• Age at least 18. -Voluntary written informed consent before performance of any study- related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.

• Female patients of child bearing potential must have a negative pregnancy test within 72 hrs of initiation of therapy. Female patients are either post-menopausal or surgically sterilized or willing to use two acceptable methods of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) during the study. Male patients must agree to use two acceptable methods for contraception for the duration of the study. Women must avoid pregnancy and men avoid fathering children while in the study.

• HIV positive patients are eligible if they are receiving at least two other active anti-HIV therapies other than zidovudine or atazanavir.

• Patients with active hepatitis B (HBV) infection are eligible if they are receiving effective anti-HBV therapy.

• Inclusion of Women and Minorities: Both men and women and members of all races and ethnic groups are eligible for this trial.

Exclusion Criteria:

• Acute active infection requiring acute therapy. Chronic therapy with potentially myelosuppressive agents is allowed provided that entry hematologic criteria are met.

• Diagnosed or treated for another malignancy within 3 years of enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy.

• Women who are pregnant or breastfeeding. Confirmation that the subject is not pregnant must be established by a negative serum B-human chorionic gonadotropin (B-hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women.

• Patient has ≥Grade 2 peripheral neuropathy

• Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any electrocardiogram (ECG) abnormality at Screening has to be documented by the investigator as not medically relevant.

• Patient has hypersensitivity to bortezomib, boron or mannitol.

• Patient has received other investigational drugs with 14 days before enrollment

• Serious medical or psychiatric illness likely to interfere with participation in this clinical study.

• 1.5x upper limit of normal (ULN) total bilirubin except if is determined to be related to Gilbert's disease or tumor biliary/liver involvement.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Miami Hospital/Sylvester	Miami	Florida	United States	33136
2	Johns Hopkins University	Baltimore	Maryland	United States	21231
3	Washington University School of Medicine	St. Louis	Missouri	United States	63110
4	Montefiore Medical Center	Bronx	New York	United States	10467
5	Columbia University, College of Physicians and Surgeons	New York	New York	United States	10032
6	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065

Sponsors and Collaborators

• Washington University School of Medicine

Investigators

• Principal Investigator: Lee Ratner, M.D., Ph.D., Washington University School of Medicine

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

Publications

• Mitra-Kaushik S, Harding JC, Hess JL, Ratner L. Effects of the proteasome inhibitor PS-341 on tumor growth in HTLV-1 Tax transgenic mice and Tax tumor transplants. Blood. 2004 Aug 1;104(3):802-9. Epub 2004 Apr 15.
• Ratner L, Harrington W, Feng X, Grant C, Jacobson S, Noy A, Sparano J, Lee J, Ambinder R, Campbell N, Lairmore M; AIDS Malignancy Consortium. Human T cell leukemia virus reactivation with progression of adult T-cell leukemia-lymphoma. PLoS One. 2009;4(2):e4420. doi: 10.1371/journal.pone.0004420. Epub 2009 Feb 10.
• Satou Y, Nosaka K, Koya Y, Yasunaga JI, Toyokuni S, Matsuoka M. Proteasome inhibitor, bortezomib, potently inhibits the growth of adult T-cell leukemia cells both in vivo and in vitro. Leukemia. 2004 Aug;18(8):1357-63.
• Tsukasaki K, Hermine O, Bazarbachi A, Ratner L, Ramos JC, Harrington W Jr, O'Mahony D, Janik JE, Bittencourt AL, Taylor GP, Yamaguchi K, Utsunomiya A, Tobinai K, Watanabe T. Definition, prognostic factors, treatment, and response criteria of adult T-cell leukemia-lymphoma: a proposal from an international consensus meeting. J Clin Oncol. 2009 Jan 20;27(3):453-9. doi: 10.1200/JCO.2008.18.2428. Epub 2008 Dec 8.

• Responsible Party: Washington University School of Medicine
• ClinicalTrials.gov Identifier: NCT01000285
• Other Study ID Numbers: 09-1758 / 201108212
• First Posted: Oct 23, 2009
• Last Update Posted: Mar 28, 2017
• Last Verified: Feb 1, 2017

• Additional relevant MeSH terms: Lymphoma; Leukemia; Leukemia, T-Cell; Leukemia-Lymphoma, Adult T-Cell; Raltegravir Potassium; Prednisone; Cyclophosphamide; Doxorubicin; Etoposide; Vincristine; Bortezomib

Study Results

Participant Flow

Recruitment Details	The study opened to participant enrollment on 12/22/2010 and closed to participant enrollment on 05/29/2014.

Arm/Group Title	EPOCH Chemotherapy & Bortezomib
Arm/Group Description	Bortezomib 1.0 mg/m2 IV Days 1-4 Etoposide 50 mg/m2/d 96 hour CIVI on Days 1-4 Vincristine 0.4 mg/m2/d 96 hour CIVI on Days 1-4 Doxorubicin 10 mg/m2/d 96 hour CIVI on Days 1-4 Prednisone 60 mg/m2/d PO on Days 1-5 Cyclophosphamide 375 mg/m2 IV on Day 5 Raltegravir 400 mg PO BID every day starting with cycle 2 therapy for the entire duration of the cycle. Cycles will be repeated every 21-28 days for 2 cycles beyond best response, or a maximum of 6 cycles.
Period Title: Overall Study
STARTED	18
COMPLETED	18
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Acute ATLL	Lymphoma ATLL	Total
Arm/Group Description	Bortezomib 1.0 mg/m2 IV Days 1-4 Etoposide 50 mg/m2/d 96 hour CIVI on Days 1-4 Vincristine 0.4 mg/m2/d 96 hour CIVI on Days 1-4 Doxorubicin 10 mg/m2/d 96 hour CIVI on Days 1-4 Prednisone 60 mg/m2/d PO on Days 1-5 Cyclophosphamide 375 mg/m2 IV on Day 5 Raltegravir 400 mg PO BID every day starting with cycle 2 therapy for the entire duration of the cycle. Cycles will be repeated every 21-28 days for 2 cycles beyond best response, or a maximum of 6 cycles.	Bortezomib 1.0 mg/m2 IV Days 1-4 Etoposide 50 mg/m2/d 96 hour CIVI on Days 1-4 Vincristine 0.4 mg/m2/d 96 hour CIVI on Days 1-4 Doxorubicin 10 mg/m2/d 96 hour CIVI on Days 1-4 Prednisone 60 mg/m2/d PO on Days 1-5 Cyclophosphamide 375 mg/m2 IV on Day 5 Raltegravir 400 mg PO BID every day starting with cycle 2 therapy for the entire duration of the cycle. Cycles will be repeated every 21-28 days for 2 cycles beyond best response, or a maximum of 6 cycles.	Total of all reporting groups
Overall Participants	6	12	18
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	51.5	56	52
Sex: Female, Male (Count of Participants)
Female	4 66.7%	10 83.3%	14 77.8%
Male	2 33.3%	2 16.7%	4 22.2%
Region of Enrollment (participants) [Number]
United States	6 100%	12 100%	18 100%
Birthplace (participants) [Number]
Antigua	0 0%	1 8.3%	1 5.6%
Dominican Republic	1 16.7%	0 0%	1 5.6%
Haiti	0 0%	3 25%	3 16.7%
Jamaica	3 50%	5 41.7%	8 44.4%
USA	1 16.7%	2 16.7%	3 16.7%
Virgin Islands	0 0%	1 8.3%	1 5.6%
Bahamas	1 16.7%	0 0%	1 5.6%

Outcome Measures

1. Primary Outcome

Title	Tolerability of Treatment as Measured by Number of Participants With Grade 3 or Higher Adverse Events
Description	The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 will be utilized for all toxicity reporting.
Time Frame	Up to 30 days after completion of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	EPOCH Chemotherapy & Bortezomib
Arm/Group Description	Bortezomib 1.0 mg/m2 IV Days 1-4 Etoposide 50 mg/m2/d 96 hour CIVI on Days 1-4 Vincristine 0.4 mg/m2/d 96 hour CIVI on Days 1-4 Doxorubicin 10 mg/m2/d 96 hour CIVI on Days 1-4 Prednisone 60 mg/m2/d PO on Days 1-5 Cyclophosphamide 375 mg/m2 IV on Day 5 Raltegravir 400 mg PO BID every day starting with cycle 2 therapy for the entire duration of the cycle. Cycles will be repeated every 21-28 days for 2 cycles beyond best response, or a maximum of 6 cycles.
Measure Participants	18
Fatigue	1 16.7%
Vomiting	1 16.7%
Spontaneous bacterial peritonitis	1 16.7%
Abdominal distension	2 33.3%
Hemoglobin	6 100%
Leukocytes (WBC)	7 116.7%
Lymphopenia	1 16.7%
Neutrophils	6 100%
Platelets	6 100%
Infection without neutropenia	1 16.7%
Infection with neutropenia	1 16.7%
Omaya port infection	1 16.7%
IV port infection	1 16.7%
Sepsis	2 33.3%
Neutropenic fever	3 50%
Hypoglycemia	1 16.7%
Hyperglycemia	2 33.3%
Magnesium	1 16.7%
Hypokalemia	1 16.7%
Hypertriglyceridemia	1 16.7%
Confusion	1 16.7%
Headache	1 16.7%
Encephalitis	1 16.7%
Abdominal pain	1 16.7%
Cough	1 16.7%
Dyspnea	1 16.7%

2. Primary Outcome

Title	Efficacy of Treatment as Measured by Best Overall Response
Description	-The response definitions used for this study are the 2007 Cheson criteria.
Time Frame	Up to 4 years following completion of therapy

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	EPOCH Chemotherapy & Bortezomib
Arm/Group Description	Bortezomib 1.0 mg/m2 IV Days 1-4 Etoposide 50 mg/m2/d 96 hour CIVI on Days 1-4 Vincristine 0.4 mg/m2/d 96 hour CIVI on Days 1-4 Doxorubicin 10 mg/m2/d 96 hour CIVI on Days 1-4 Prednisone 60 mg/m2/d PO on Days 1-5 Cyclophosphamide 375 mg/m2 IV on Day 5 Raltegravir 400 mg PO BID every day starting with cycle 2 therapy for the entire duration of the cycle. Cycles will be repeated every 21-28 days for 2 cycles beyond best response, or a maximum of 6 cycles.
Measure Participants	18
Progressive Disease	3 50%
Stable disease	3 50%
Partial response	9 150%
Complete response	3 50%

3. Secondary Outcome

Title	Time to Progression
Description	-The progression definitions used for this study are from the 2007 Cheson criteria.
Time Frame	Up to 4 years following completion of therapy

Outcome Measure Data

Analysis Population Description

12 out of the 18 participants had a complete or partial response.

Arm/Group Title	EPOCH Chemotherapy & Bortezomib
Arm/Group Description	Bortezomib 1.0 mg/m2 IV Days 1-4 Etoposide 50 mg/m2/d 96 hour CIVI on Days 1-4 Vincristine 0.4 mg/m2/d 96 hour CIVI on Days 1-4 Doxorubicin 10 mg/m2/d 96 hour CIVI on Days 1-4 Prednisone 60 mg/m2/d PO on Days 1-5 Cyclophosphamide 375 mg/m2 IV on Day 5 Raltegravir 400 mg PO BID every day starting with cycle 2 therapy for the entire duration of the cycle. Cycles will be repeated every 21-28 days for 2 cycles beyond best response, or a maximum of 6 cycles.
Measure Participants	18
Best response of complete response	199
Best response of partial response	143
Best response of stable disease	88
All participants	127

4. Secondary Outcome

Title	Effects of on HTLV-1 DNA After Treatment as Measured by Proviral Loads
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Responders	Non-responders
Arm/Group Description	Patients who had a complete or partial response to treatment	Patients who had stable or progressive disease after treatment.
Measure Participants	12	6
Baseline	0.372 (0.123)	0.417 (0.045)
Study completion	0.0128 (0.023)	0.033 (0.147)

5. Secondary Outcome

Title	Relation of NFκB Gene Expression Profile on Response
Description	Standard error represents the standard error of the fold expression of protein coding transcripts for each gene indicated.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

Average RPKM values normalized to Patient A before therapy.

Arm/Group Title	Patient A (Responder) Pre-Therapy	Patient A (Responder) Post-Therapy	Patient B (Responder) Pre-Therapy	Patient B (Responder) Post-Therapy	Patient C (Non-responder) Pre-Therapy	Patient C (Non-responder) Post-Therapy	Patient D (Non-responder) Pre-Therapy	Patient D (Non-responder) Post-Therapy
Arm/Group Description
Measure Participants	1	1	1	1	1	1	1	1
BLK	1.000 (0.000)	0.178 (0.015)	0.889 (0.150)	0.172 (0.073)	68.856 (10.543)	77.590 (12.715)	233.179 (60.619)	46.801 (13.193)
CADMI	1.000 (0.000)	0.011 (0.001)	0.623 (0.031)	0.007 (0.001)	1.494 (0.190)	1.816 (0.105)	2.013 (0.085)	0.470 (0.026)
CD25	1.000 (0.000)	0.035 (0.006)	0.303 (0.013)	0.015 (0.003)	0.862 (0.013)	0.691 (0.013)	2.897 (0.098)	0.512 (0.023)
CD4	1.000 (0.000)	1.380 (0.047)	1.437 (0.080)	0.607 (0.023)	1.319 (0.075)	1.923 (0.092)	3.057 (0.340)	0.648 (0.056)
CD45	1.000 (0.000)	1.718 (0.045)	2.049 (0.035)	0.959 (0.016)	1.163 (0.021)	1.640 (0.039)	0.594 (0.008)	0.714 (0.019)

6. Secondary Outcome

Title	Effects of HTLV-1 RNA Load After Treatment as Measured by Hbz Messenger RNA
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Responders	Non-responders
Arm/Group Description	Patients who had a complete or partial response to treatment	Patients who had stable or progressive disease after treatment.
Measure Participants	12	6
Baseline	37.0 (11.9)	41.9 (29.1)
Study completion	7.33 (2.76)	35.7 (23.7)

7. Secondary Outcome

Title	Effects of HTLV-1 Integrase Gene Sequence After Treatment as Measured by Nucleotide Divergence
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	EPOCH Chemotherapy & Bortezomib
Arm/Group Description	Bortezomib 1.0 mg/m2 IV Days 1-4 Etoposide 50 mg/m2/d 96 hour CIVI on Days 1-4 Vincristine 0.4 mg/m2/d 96 hour CIVI on Days 1-4 Doxorubicin 10 mg/m2/d 96 hour CIVI on Days 1-4 Prednisone 60 mg/m2/d PO on Days 1-5 Cyclophosphamide 375 mg/m2 IV on Day 5 Raltegravir 400 mg PO BID every day starting with cycle 2 therapy for the entire duration of the cycle. Cycles will be repeated every 21-28 days for 2 cycles beyond best response, or a maximum of 6 cycles.
Measure Participants	18
Baseline	0.49 (0.05)
Study completion	0.52 (0.06)

8. Secondary Outcome

Title	Effects of HTLV-1 Integration Sites After Treatment
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	EPOCH Chemotherapy & Bortezomib
Arm/Group Description	Bortezomib 1.0 mg/m2 IV Days 1-4 Etoposide 50 mg/m2/d 96 hour CIVI on Days 1-4 Vincristine 0.4 mg/m2/d 96 hour CIVI on Days 1-4 Doxorubicin 10 mg/m2/d 96 hour CIVI on Days 1-4 Prednisone 60 mg/m2/d PO on Days 1-5 Cyclophosphamide 375 mg/m2 IV on Day 5 Raltegravir 400 mg PO BID every day starting with cycle 2 therapy for the entire duration of the cycle. Cycles will be repeated every 21-28 days for 2 cycles beyond best response, or a maximum of 6 cycles.
Measure Participants	18
Baseline	1.31 (0.31)
Study completion	1.00 (0.22)

Adverse Events

Arm/Group Title	EPOCH Chemotherapy & Bortezomib
Arm/Group Description	Bortezomib 1.0 mg/m2 IV Days 1-4 Etoposide 50 mg/m2/d 96 hour CIVI on Days 1-4 Vincristine 0.4 mg/m2/d 96 hour CIVI on Days 1-4 Doxorubicin 10 mg/m2/d 96 hour CIVI on Days 1-4 Prednisone 60 mg/m2/d PO on Days 1-5 Cyclophosphamide 375 mg/m2 IV on Day 5 Raltegravir 400 mg PO BID every day starting with cycle 2 therapy for the entire duration of the cycle. Cycles will be repeated every 21-28 days for 2 cycles beyond best response, or a maximum of 6 cycles.
All Cause Mortality
	EPOCH Chemotherapy & Bortezomib
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	EPOCH Chemotherapy & Bortezomib
	Affected / at Risk (%)	# Events
Total	1/18 (5.6%)
Infections and infestations
Sepsis	1/18 (5.6%)	18
Other (Not Including Serious) Adverse Events
	EPOCH Chemotherapy & Bortezomib
	Affected / at Risk (%)	# Events
Total	18/18 (100%)
Blood and lymphatic system disorders
Hemoglobin	11/18 (61.1%)
Eye disorders
Blurred vision	1/18 (5.6%)
Dry eyes	1/18 (5.6%)
Gastrointestinal disorders
Abdominal distension	2/18 (11.1%)
Abdominal pain	2/18 (11.1%)
Constipation	2/18 (11.1%)
Dysgeusia	1/18 (5.6%)
GI bleed/ulcers	1/18 (5.6%)
Indigestion	2/18 (11.1%)
Mucositis	3/18 (16.7%)
Nausea	2/18 (11.1%)
Spontaneous bacterial peritonitis	1/18 (5.6%)
Vomiting	2/18 (11.1%)
General disorders
Chills	1/18 (5.6%)
Edema	2/18 (11.1%)
Fatigue	8/18 (44.4%)
Fever	2/18 (11.1%)
Infections and infestations
Encephaltis	1/18 (5.6%)
IV port infection	1/18 (5.6%)
Infection with neutropenia	1/18 (5.6%)
Infection without neutropenia	2/18 (11.1%)
Neutropenic fever	3/18 (16.7%)
Omaya port infection	1/18 (5.6%)
Sepsis	1/18 (5.6%)
Septic arthritis	1/18 (5.6%)
Sinusitis	1/18 (5.6%)
Vaginal infection	1/18 (5.6%)
Investigations
Alkaline phosphtase	4/18 (22.2%)
Leukocytes (WBC)	8/18 (44.4%)
Lymphopenia	1/18 (5.6%)
Neutrophils (ANC)	7/18 (38.9%)
Platelets	8/18 (44.4%)
SGOT (AST)	4/18 (22.2%)
SGPT (ALT)	4/18 (22.2%)
Weight loss	1/18 (5.6%)
Metabolism and nutrition disorders
Albumin	4/18 (22.2%)
Anorexia	2/18 (11.1%)
Dehydration	1/18 (5.6%)
Hypercalcemia	3/18 (16.7%)
Hyperglycemia	4/18 (22.2%)
Hypernatremia	1/18 (5.6%)
Hypertriglyceridemia	1/18 (5.6%)
Hypocalcemia	2/18 (11.1%)
Hypoglycemia	2/18 (11.1%)
Hypokalemia	4/18 (22.2%)
Hyponatremia	4/18 (22.2%)
Hypophosphatemia	2/18 (11.1%)
Magnesium	3/18 (16.7%)
Uric acid	1/18 (5.6%)
Musculoskeletal and connective tissue disorders
Back pain	1/18 (5.6%)
Bone pain	2/18 (11.1%)
Extremity pain	1/18 (5.6%)
Nervous system disorders
Headache	3/18 (16.7%)
Opthalmoplegia/laryngeal/aphasia	1/18 (5.6%)
Seizure	1/18 (5.6%)
Sensory neuropathy	9/18 (50%)
Psychiatric disorders
Confusion	2/18 (11.1%)
Renal and urinary disorders
Creatinine	2/18 (11.1%)
Respiratory, thoracic and mediastinal disorders
Congestion	1/18 (5.6%)
Cough	4/18 (22.2%)
Dyspnea	1/18 (5.6%)
Rhinorrhea	1/18 (5.6%)
Skin and subcutaneous tissue disorders
Alopecia	1/18 (5.6%)
Dry skin	1/18 (5.6%)
Nail discoloration	1/18 (5.6%)
Pigment changes	1/18 (5.6%)
Rash	1/18 (5.6%)
Vascular disorders
Hypertension	1/18 (5.6%)

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.