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Trial record 39 of 65 for:    HTLV

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

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ClinicalTrials.gov Identifier: NCT01000285
Recruitment Status : Completed
First Posted : October 23, 2009
Results First Posted : December 13, 2016
Last Update Posted : March 28, 2017
Sponsor:
Information provided by (Responsible Party):
Washington University School of Medicine

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Leukemia-Lymphoma, Adult T-Cell
Interventions Drug: Bortezomib
Drug: Etoposide
Drug: Vincristine
Drug: Doxorubicin
Drug: Prednisone
Drug: Cyclophosphamide
Drug: Raltegravir
Enrollment 18
Recruitment Details The study opened to participant enrollment on 12/22/2010 and closed to participant enrollment on 05/29/2014.
Pre-assignment Details  
Arm/Group Title EPOCH Chemotherapy & Bortezomib
Hide 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
Arm/Group Title Acute ATLL Lymphoma ATLL Total
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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 Number of Baseline Participants 6 12 18
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 6 participants 12 participants 18 participants
51.5
(38 to 70)
56
(36 to 76)
52
(36 to 76)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 12 participants 18 participants
Female
4
  66.7%
10
  83.3%
14
  77.8%
Male
2
  33.3%
2
  16.7%
4
  22.2%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 6 participants 12 participants 18 participants
6 12 18
Birthplace  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 6 participants 12 participants 18 participants
Antigua 0 1 1
Dominican Republic 1 0 1
Haiti 0 3 3
Jamaica 3 5 8
USA 1 2 3
Virgin Islands 0 1 1
Bahamas 1 0 1
1.Primary Outcome
Title Tolerability of Treatment as Measured by Number of Participants With Grade 3 or Higher Adverse Events
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title EPOCH Chemotherapy & Bortezomib
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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.

Overall Number of Participants Analyzed 18
Measure Type: Number
Unit of Measure: participants
Fatigue 1
Vomiting 1
Spontaneous bacterial peritonitis 1
Abdominal distension 2
Hemoglobin 6
Leukocytes (WBC) 7
Lymphopenia 1
Neutrophils 6
Platelets 6
Infection without neutropenia 1
Infection with neutropenia 1
Omaya port infection 1
IV port infection 1
Sepsis 2
Neutropenic fever 3
Hypoglycemia 1
Hyperglycemia 2
Magnesium 1
Hypokalemia 1
Hypertriglyceridemia 1
Confusion 1
Headache 1
Encephalitis 1
Abdominal pain 1
Cough 1
Dyspnea 1
2.Primary Outcome
Title Efficacy of Treatment as Measured by Best Overall Response
Hide Description -The response definitions used for this study are the 2007 Cheson criteria.
Time Frame Up to 4 years following completion of therapy
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title EPOCH Chemotherapy & Bortezomib
Hide 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.

Overall Number of Participants Analyzed 18
Measure Type: Number
Unit of Measure: participants
Progressive Disease 3
Stable disease 3
Partial response 9
Complete response 3
3.Secondary Outcome
Title Time to Progression
Hide Description -The progression definitions used for this study are from the 2007 Cheson criteria.
Time Frame Up to 4 years following completion of therapy
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Hide Analysis Population Description
12 out of the 18 participants had a complete or partial response.
Arm/Group Title EPOCH Chemotherapy & Bortezomib
Hide 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.

Overall Number of Participants Analyzed 18
Median (Full Range)
Unit of Measure: days
Best response of complete response
199
(190 to 864)
Best response of partial response
143
(85 to 240)
Best response of stable disease
88
(55 to 116)
All participants
127
(23 to 864)
4.Secondary Outcome
Title Effects of on HTLV-1 DNA After Treatment as Measured by Proviral Loads
Hide Description [Not Specified]
Time Frame 6 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Responders Non-responders
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Patients who had a complete or partial response to treatment
Patients who had stable or progressive disease after treatment.
Overall Number of Participants Analyzed 12 6
Mean (Standard Error)
Unit of Measure: copies/peripheral blood mononuclear cell
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
Hide Description Standard error represents the standard error of the fold expression of protein coding transcripts for each gene indicated.
Time Frame 6 months
Show Outcome Measure DataHide Outcome Measure Data
Hide 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
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
[Not Specified]
[Not Specified]
[Not Specified]
[Not Specified]
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 1 1 1 1 1 1 1 1
Mean (Standard Error)
Unit of Measure: fold expression
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
Hide Description [Not Specified]
Time Frame 6 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Responders Non-responders
Hide Arm/Group Description:
Patients who had a complete or partial response to treatment
Patients who had stable or progressive disease after treatment.
Overall Number of Participants Analyzed 12 6
Mean (Standard Error)
Unit of Measure: copies/peripheral blood mononuclear cell
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
Hide Description [Not Specified]
Time Frame 6 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title EPOCH Chemotherapy & Bortezomib
Hide 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.

Overall Number of Participants Analyzed 18
Mean (Standard Error)
Unit of Measure: percentage of nucleotide divergence
Baseline 0.49  (0.05)
Study completion 0.52  (0.06)
8.Secondary Outcome
Title Effects of HTLV-1 Integration Sites After Treatment
Hide Description [Not Specified]
Time Frame 6 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title EPOCH Chemotherapy & Bortezomib
Hide 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.

Overall Number of Participants Analyzed 18
Mean (Standard Error)
Unit of Measure: number of integration sites
Baseline 1.31  (0.31)
Study completion 1.00  (0.22)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title EPOCH Chemotherapy & Bortezomib
Hide 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 (%)
Total   --/--    
Show Serious Adverse Events Hide Serious Adverse Events
EPOCH Chemotherapy & Bortezomib
Affected / at Risk (%) # Events
Total   1/18 (5.56%)    
Infections and infestations   
Sepsis  1  1/18 (5.56%)  18
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE (3.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
EPOCH Chemotherapy & Bortezomib
Affected / at Risk (%) # Events
Total   18/18 (100.00%)    
Blood and lymphatic system disorders   
Hemoglobin  1  11/18 (61.11%) 
Eye disorders   
Blurred vision  1  1/18 (5.56%) 
Dry eyes  1  1/18 (5.56%) 
Gastrointestinal disorders   
Abdominal distension  1  2/18 (11.11%) 
Abdominal pain  1  2/18 (11.11%) 
Constipation  1  2/18 (11.11%) 
Dysgeusia  1  1/18 (5.56%) 
GI bleed/ulcers  1  1/18 (5.56%) 
Indigestion  1  2/18 (11.11%) 
Mucositis  1  3/18 (16.67%) 
Nausea  1  2/18 (11.11%) 
Spontaneous bacterial peritonitis  1  1/18 (5.56%) 
Vomiting  1  2/18 (11.11%) 
General disorders   
Chills  1  1/18 (5.56%) 
Edema  1  2/18 (11.11%) 
Fatigue  1  8/18 (44.44%) 
Fever  1  2/18 (11.11%) 
Infections and infestations   
Encephaltis  1  1/18 (5.56%) 
IV port infection  1  1/18 (5.56%) 
Infection with neutropenia  1  1/18 (5.56%) 
Infection without neutropenia  1  2/18 (11.11%) 
Neutropenic fever  1  3/18 (16.67%) 
Omaya port infection  1  1/18 (5.56%) 
Sepsis  1  1/18 (5.56%) 
Septic arthritis  1  1/18 (5.56%) 
Sinusitis  1  1/18 (5.56%) 
Vaginal infection  1  1/18 (5.56%) 
Investigations   
Alkaline phosphtase  1  4/18 (22.22%) 
Leukocytes (WBC)  1  8/18 (44.44%) 
Lymphopenia  1  1/18 (5.56%) 
Neutrophils (ANC)  1  7/18 (38.89%) 
Platelets  1  8/18 (44.44%) 
SGOT (AST)  1  4/18 (22.22%) 
SGPT (ALT)  1  4/18 (22.22%) 
Weight loss  1  1/18 (5.56%) 
Metabolism and nutrition disorders   
Albumin  1  4/18 (22.22%) 
Anorexia  1  2/18 (11.11%) 
Dehydration  1  1/18 (5.56%) 
Hypercalcemia  1  3/18 (16.67%) 
Hyperglycemia  1  4/18 (22.22%) 
Hypernatremia  1  1/18 (5.56%) 
Hypertriglyceridemia  1  1/18 (5.56%) 
Hypocalcemia  1  2/18 (11.11%) 
Hypoglycemia  1  2/18 (11.11%) 
Hypokalemia  1  4/18 (22.22%) 
Hyponatremia  1  4/18 (22.22%) 
Hypophosphatemia  1  2/18 (11.11%) 
Magnesium  1  3/18 (16.67%) 
Uric acid  1  1/18 (5.56%) 
Musculoskeletal and connective tissue disorders   
Back pain  1  1/18 (5.56%) 
Bone pain  1  2/18 (11.11%) 
Extremity pain  1  1/18 (5.56%) 
Nervous system disorders   
Headache  1  3/18 (16.67%) 
Opthalmoplegia/laryngeal/aphasia  1  1/18 (5.56%) 
Seizure  1  1/18 (5.56%) 
Sensory neuropathy  1  9/18 (50.00%) 
Psychiatric disorders   
Confusion  1  2/18 (11.11%) 
Renal and urinary disorders   
Creatinine  1  2/18 (11.11%) 
Respiratory, thoracic and mediastinal disorders   
Congestion  1  1/18 (5.56%) 
Cough  1  4/18 (22.22%) 
Dyspnea  1  1/18 (5.56%) 
Rhinorrhea  1  1/18 (5.56%) 
Skin and subcutaneous tissue disorders   
Alopecia  1  1/18 (5.56%) 
Dry skin  1  1/18 (5.56%) 
Nail discoloration  1  1/18 (5.56%) 
Pigment changes  1  1/18 (5.56%) 
Rash  1  1/18 (5.56%) 
Vascular disorders   
Hypertension  1  1/18 (5.56%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE (3.0)
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Name/Title: Lee Ratner, M.D., Ph.D.
Organization: Washington University School of Medicine
Phone: 314-362-8836
Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT01000285     History of Changes
Other Study ID Numbers: 09-1758 / 201108212
First Submitted: October 19, 2009
First Posted: October 23, 2009
Results First Submitted: October 19, 2016
Results First Posted: December 13, 2016
Last Update Posted: March 28, 2017