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Trial record 14 of 23 for:    CD20 Fred Hutchinson

Bortezomib and Vorinostat as Maintenance Therapy After Autologous Stem Cell Transplant in Treating Patients With Non-Hodgkin Lymphoma

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ClinicalTrials.gov Identifier: NCT00992446
Recruitment Status : Completed
First Posted : October 9, 2009
Results First Posted : May 10, 2017
Last Update Posted : June 12, 2017
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Leona Holmberg, Fred Hutchinson Cancer Research Center

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Adult Diffuse Large B-Cell Lymphoma
B-Cell Non-Hodgkin Lymphoma
Follicular Lymphoma
Mantle Cell Lymphoma
Non-Hodgkin Lymphoma
T-Cell Non-Hodgkin Lymphoma
Interventions Procedure: Autologous Hematopoietic Stem Cell Transplantation
Drug: Bortezomib
Drug: Carmustine
Drug: Cytarabine
Drug: Etoposide
Drug: Melphalan
Drug: Rituximab
Drug: Vorinostat
Enrollment 27
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Treatment (Chemotherapy, ASCT, Bortezomib, Vorinostat))
Hide Arm/Group Description

All patients receive carmustine IV over 3 hours on day -7; cytarabine IV BID over 3 hours and etoposide IV BID over 2 hours on days -6 to -3; and melphalan IV over 30 minutes on day -2. Only patients with history of CD20+ NHL receive additional rituximab IV on days -19 and -12. Patients undergo ASCT on day 0. Patients then receive bortezomib IV on days 2 and 8, and vorinostat PO QD on days 1-14. Treatment with bortezomib and vorinostat repeats for total of 12 courses in the absence of disease progression or unacceptable toxicity.

Autologous Hematopoietic Stem Cell Transplantation: Undergo ASCT

Bortezomib: Given IV

Carmustine: Given IV

Cytarabine: Given IV

Etoposide: Given IV

Melphalan: Given IV

Rituximab: Given IV

Vorinostat: Given PO

Period Title: Overall Study
Started 27
Completed 19
Not Completed 8
Reason Not Completed
Disease Progression             1
Withdrawal by Subject             2
Maintenance Therapy Screen Fail             5
Arm/Group Title Treatment (Chemotherapy, ASCT, Bortezomib, Vorinostat))
Hide Arm/Group Description

All patients receive carmustine IV over 3 hours on day -7; cytarabine IV BID over 3 hours and etoposide IV BID over 2 hours on days -6 to -3; and melphalan IV over 30 minutes on day -2. Only patients with history of CD20+ NHL receive additional rituximab IV on days -19 and -12. Patients undergo ASCT on day 0. Patients then receive bortezomib IV on days 2 and 8, and vorinostat PO QD on days 1-14. Treatment with bortezomib and vorinostat repeats for total of 12 courses in the absence of disease progression or unacceptable toxicity.

Autologous Hematopoietic Stem Cell Transplantation: Undergo ASCT

Bortezomib: Given IV

Carmustine: Given IV

Cytarabine: Given IV

Etoposide: Given IV

Melphalan: Given IV

Rituximab: Given IV

Vorinostat: Given PO

Overall Number of Baseline Participants 27
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 27 participants
<=18 years
0
   0.0%
Between 18 and 65 years
16
  59.3%
>=65 years
11
  40.7%
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 27 participants
61
(39 to 69)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 27 participants
Female
7
  25.9%
Male
20
  74.1%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 27 participants
Hispanic or Latino
1
   3.7%
Not Hispanic or Latino
26
  96.3%
Unknown or Not Reported
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 27 participants
American Indian or Alaska Native
0
   0.0%
Asian
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
0
   0.0%
White
27
 100.0%
More than one race
0
   0.0%
Unknown or Not Reported
0
   0.0%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 27 participants
27
 100.0%
1.Primary Outcome
Title Toxicity of Vorinostat Bortezomib Maintenance Therapy After Autologous Transplant
Hide Description Number of patients on maintenance therapy post-transplant who experienced grade 3 or higher toxicity per NCI-Common Terminology Criteria for Adverse Events, version 3. The first three months of bortezomib and vorinostat therapy will be used as the time period to evaluate toxicity for stopping rules of the study. Toxicity that meets stopping rules will be determined based on the number of patients that are withdrawn from study for significant toxicity (grade IV, non-hematological, non-metabolic, non-peripheral neuropathy).
Time Frame 3 months after start of maintenance therapy
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Treatment (Chemotherapy, ASCT, Bortezomib, Vorinostat))
Hide Arm/Group Description:

All patients receive carmustine IV over 3 hours on day -7; cytarabine IV BID over 3 hours and etoposide IV BID over 2 hours on days -6 to -3; and melphalan IV over 30 minutes on day -2. Only patients with history of CD20+ NHL receive additional rituximab IV on days -19 and -12. Patients undergo ASCT on day 0. Patients then receive bortezomib IV on days 2 and 8, and vorinostat PO QD on days 1-14. Treatment with bortezomib and vorinostat repeats for total of 12 courses in the absence of disease progression or unacceptable toxicity.

Autologous Hematopoietic Stem Cell Transplantation: Undergo ASCT

Bortezomib: Given IV

Carmustine: Given IV

Cytarabine: Given IV

Etoposide: Given IV

Melphalan: Given IV

Rituximab: Given IV

Vorinostat: Given PO

Overall Number of Participants Analyzed 19
Measure Type: Count of Participants
Unit of Measure: Participants
1
   5.3%
2.Secondary Outcome
Title Median Time to Disease Progression
Hide Description (Not enough follow-up to report. 6/17/2018 is when this outcome measure will be met)
Time Frame 3 Years Post-Transplant
Outcome Measure Data Not Reported
3.Secondary Outcome
Title Ability to Complete Planned 12 Cycles of Maintenance Therapy
Hide Description Number of patients who completed all 12 cycles of maintenance therapy.
Time Frame Approximately 12 months following start of maintenance therapy
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Treatment (Chemotherapy, ASCT, Bortezomib, Vorinostat))
Hide Arm/Group Description:

All patients receive carmustine IV over 3 hours on day -7; cytarabine IV BID over 3 hours and etoposide IV BID over 2 hours on days -6 to -3; and melphalan IV over 30 minutes on day -2. Only patients with history of CD20+ NHL receive additional rituximab IV on days -19 and -12. Patients undergo ASCT on day 0. Patients then receive bortezomib IV on days 2 and 8, and vorinostat PO QD on days 1-14. Treatment with bortezomib and vorinostat repeats for total of 12 courses in the absence of disease progression or unacceptable toxicity.

Autologous Hematopoietic Stem Cell Transplantation: Undergo ASCT

Bortezomib: Given IV

Carmustine: Given IV

Cytarabine: Given IV

Etoposide: Given IV

Melphalan: Given IV

Rituximab: Given IV

Vorinostat: Given PO

Overall Number of Participants Analyzed 19
Measure Type: Count of Participants
Unit of Measure: Participants
Completed 12 Cycles of Maintenance Therapy
7
  36.8%
Unable to complete therapy due to relapse
3
  15.8%
Withdrawl at patient request
2
  10.5%
Unable to complete due to toxicities
5
  26.3%
PI decision due to increasing creatinine levels
1
   5.3%
Patient left state
1
   5.3%
4.Secondary Outcome
Title Overall Survival
Hide Description (Not enough follow-up to report. 6/17/2018 is when this outcome measure will be met)
Time Frame 3 Years Post-Transplant
Outcome Measure Data Not Reported
5.Secondary Outcome
Title Event-free Survival
Hide Description (Not enough follow-up to report. 6/17/2018 is when this outcome measure will be met)
Time Frame 3 Years Post-Transplant
Outcome Measure Data Not Reported
Time Frame [Not Specified]
Adverse Event Reporting Description Adverse events will be evaluated according to criteria outlined in the NCI Common Terminology Criteria for Adverse Events (CTCAE), version 3.0., except hematological toxicity. Grade 3 or higher reported.
 
Arm/Group Title Treatment (Chemotherapy, ASCT, Bortezomib, Vorinostat))
Hide Arm/Group Description

All patients receive carmustine IV over 3 hours on day -7; cytarabine IV BID over 3 hours and etoposide IV BID over 2 hours on days -6 to -3; and melphalan IV over 30 minutes on day -2. Only patients with history of CD20+ NHL receive additional rituximab IV on days -19 and -12. Patients undergo ASCT on day 0. Patients then receive bortezomib IV on days 2 and 8, and vorinostat PO QD on days 1-14. Treatment with bortezomib and vorinostat repeats for total of 12 courses in the absence of disease progression or unacceptable toxicity.

Autologous Hematopoietic Stem Cell Transplantation: Undergo ASCT

Bortezomib: Given IV

Carmustine: Given IV

Cytarabine: Given IV

Etoposide: Given IV

Melphalan: Given IV

Rituximab: Given IV

Vorinostat: Given PO

All-Cause Mortality
Treatment (Chemotherapy, ASCT, Bortezomib, Vorinostat))
Affected / at Risk (%)
Total   7/27 (25.93%) 
Show Serious Adverse Events Hide Serious Adverse Events
Treatment (Chemotherapy, ASCT, Bortezomib, Vorinostat))
Affected / at Risk (%)
Total   9/27 (33.33%) 
Blood and lymphatic system disorders   
Febrile neutropenia  [1]  2/27 (7.41%) 
Cardiac disorders   
Atrial flutter/atrial fibrillation  [2]  2/27 (7.41%) 
Gastrointestinal disorders   
Abdominal pain/diarrhea  [3]  1/27 (3.70%) 
Nausea, vomiting, and diarrhea requiring hospitalization  [2]  2/27 (7.41%) 
Colitis  [2]  1/27 (3.70%) 
Infections and infestations   
Pneumonia  [4]  2/27 (7.41%) 
Indicates events were collected by systematic assessment
[1]
Transplant toxicity. One patient had both febrile neutropenia with transplant and pneumonia with maintenance therapy as two separate events.
[2]
Transplant toxicity.
[3]
Maintenance therapy toxicity.
[4]
Maintenance therapy toxicity. One patient had both febrile neutropenia with transplant and pneumonia with maintenance therapy as two separate events.
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Treatment (Chemotherapy, ASCT, Bortezomib, Vorinostat))
Affected / at Risk (%)
Total   27/27 (100.00%) 
Blood and lymphatic system disorders   
Anemia  [1]  3/27 (11.11%) 
Febrile neutropenia  [1]  21/27 (77.78%) 
Methemoglobinemia  [2]  1/19 (5.26%) 
Gastrointestinal disorders   
Colitis  [1]  2/27 (7.41%) 
Diarrhea  [1]  6/27 (22.22%) 
Heartburn  [1]  2/27 (7.41%) 
Nausea/Vomitting  [1]  7/27 (25.93%) 
Nausea  [1]  6/27 (22.22%) 
Mucositis  [1]  16/27 (59.26%) 
General disorders   
Auto GVHD  [1]  2/27 (7.41%) 
Volume overload  [1]  2/27 (7.41%) 
Investigations   
Neutropenia  [1]  27/27 (100.00%) 
Thrombocytopenia  [1]  27/27 (100.00%) 
Neutropenia  [2]  13/19 (68.42%) 
Thrombocytopenia  [2]  2/19 (10.53%) 
Metabolism and nutrition disorders   
Dehydration  [1]  3/27 (11.11%) 
Hyponatremia  [2]  1/19 (5.26%) 
Nervous system disorders   
Dizziness  [2]  1/19 (5.26%) 
Peripheral neuropathy  [2]  2/19 (10.53%) 
Skin and subcutaneous tissue disorders   
Rash  [1]  2/27 (7.41%) 
Indicates events were collected by systematic assessment
[1]
Autologous transplant adverse event. No patients died due to transplant therapy.
[2]
Maintenance therapy post-transplant adverse event. No patients died due to maintenance therapy.
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
Layout table for Results Point of Contact information
Name/Title: Dr. Leona A. Holmberg
Organization: Fred Hutchinson Cancer Research Center
Phone: 206-667-6447
EMail: lholmber@fredhutch.org
Layout table for additonal information
Responsible Party: Leona Holmberg, Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier: NCT00992446     History of Changes
Other Study ID Numbers: 2292.00
NCI-2009-01302 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
FH 2292/X05287 ( Other Identifier: Fred Hutchinson Cancer Research Center )
X05287
2292.00 ( Other Identifier: Fred Hutchinson Cancer Research Center )
P30CA015704 ( U.S. NIH Grant/Contract )
First Submitted: October 7, 2009
First Posted: October 9, 2009
Results First Submitted: March 31, 2017
Results First Posted: May 10, 2017
Last Update Posted: June 12, 2017