Trial Outcomes & Findings for Bortezomib and Vorinostat as Maintenance Therapy After Autologous Stem Cell Transplant in Treating Patients With Non-Hodgkin Lymphoma (NCT NCT00992446)
NCT ID: NCT00992446
Last Updated: 2020-03-18
Results Overview
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 Toxicity that meets stopping rules will be determined based on the number of patients that are withdrawn from study for significant toxicity (grade IV, non-hematological, non-metabolic, non-peripheral neuropathy).
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
27 participants
Primary outcome timeframe
3 months after start of maintenance therapy
Results posted on
2020-03-18
Participant Flow
Participant milestones
| Measure |
Treatment (Chemotherapy, ASCT, Bortezomib, Vorinostat))
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 Study
STARTED
|
27
|
|
Overall Study
COMPLETED
|
19
|
|
Overall Study
NOT COMPLETED
|
8
|
Reasons for withdrawal
| Measure |
Treatment (Chemotherapy, ASCT, Bortezomib, Vorinostat))
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 Study
Disease Progression
|
1
|
|
Overall Study
Withdrawal by Subject
|
2
|
|
Overall Study
Maintenance Therapy Screen Fail
|
5
|
Baseline Characteristics
Bortezomib and Vorinostat as Maintenance Therapy After Autologous Stem Cell Transplant in Treating Patients With Non-Hodgkin Lymphoma
Baseline characteristics by cohort
| Measure |
Treatment (Chemotherapy, ASCT, Bortezomib, Vorinostat))
n=27 Participants
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
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
16 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
11 Participants
n=5 Participants
|
|
Age, Continuous
|
61 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
7 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
20 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
26 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
26 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
27 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 3 months after start of maintenance therapyNumber 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).
Outcome measures
| Measure |
Treatment (Chemotherapy, ASCT, Bortezomib, Vorinostat))
n=19 Participants
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
|
|---|---|
|
Toxicity of Vorinostat Bortezomib Maintenance Therapy After Autologous Transplant
|
19 Participants
|
SECONDARY outcome
Timeframe: time post ASCT to progressionPopulation: median time to progression /relapse
median days from transplant to relapse/progression
Outcome measures
| Measure |
Treatment (Chemotherapy, ASCT, Bortezomib, Vorinostat))
n=19 Participants
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
|
|---|---|
|
Median Time to Disease Progression
|
1.05 years
Interval 0.41 to 8.05
|
SECONDARY outcome
Timeframe: Approximately 12 months following start of maintenance therapyNumber of patients who completed all 12 cycles of maintenance therapy.
Outcome measures
| Measure |
Treatment (Chemotherapy, ASCT, Bortezomib, Vorinostat))
n=19 Participants
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
|
|---|---|
|
Ability to Complete Planned 12 Cycles of Maintenance Therapy
Unable to complete due to toxicities
|
5 Participants
|
|
Ability to Complete Planned 12 Cycles of Maintenance Therapy
PI decision due to increasing creatinine levels
|
1 Participants
|
|
Ability to Complete Planned 12 Cycles of Maintenance Therapy
Patient left state
|
1 Participants
|
|
Ability to Complete Planned 12 Cycles of Maintenance Therapy
Completed 12 Cycles of Maintenance Therapy
|
7 Participants
|
|
Ability to Complete Planned 12 Cycles of Maintenance Therapy
Unable to complete therapy due to relapse
|
3 Participants
|
|
Ability to Complete Planned 12 Cycles of Maintenance Therapy
Withdrawl at patient request
|
2 Participants
|
SECONDARY outcome
Timeframe: 6.64 Years Post-TransplantNumber of patients alive who received maintenance therapy
Outcome measures
| Measure |
Treatment (Chemotherapy, ASCT, Bortezomib, Vorinostat))
n=19 Participants
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 Survival
Alive
|
16 participants
|
|
Overall Survival
Dead
|
3 participants
|
SECONDARY outcome
Timeframe: 6.64 Years Post-TransplantNumber of patients alive without disease progression/relapse
Outcome measures
| Measure |
Treatment (Chemotherapy, ASCT, Bortezomib, Vorinostat))
n=19 Participants
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
|
|---|---|
|
Event-free Survival
alive with disease progression
|
5 Participants
|
|
Event-free Survival
Alive without disease porgression
|
14 Participants
|
Adverse Events
Treatment (Chemotherapy, ASCT, Bortezomib, Vorinostat))
Serious events: 9 serious events
Other events: 27 other events
Deaths: 7 deaths
Serious adverse events
| Measure |
Treatment (Chemotherapy, ASCT, Bortezomib, Vorinostat))
n=27 participants at risk
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
|
|---|---|
|
Cardiac disorders
Atrial flutter/atrial fibrillation
|
7.4%
2/27
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.
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
7.4%
2/27
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.
|
|
Gastrointestinal disorders
Abdominal pain/diarrhea
|
3.7%
1/27
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.
|
|
Infections and infestations
Pneumonia
|
7.4%
2/27
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.
|
|
Gastrointestinal disorders
Nausea, vomiting, and diarrhea requiring hospitalization
|
7.4%
2/27
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.
|
|
Gastrointestinal disorders
Colitis
|
3.7%
1/27
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.
|
Other adverse events
| Measure |
Treatment (Chemotherapy, ASCT, Bortezomib, Vorinostat))
n=27 participants at risk
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
|
|---|---|
|
Blood and lymphatic system disorders
Anemia
|
11.1%
3/27
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.
|
|
General disorders
Auto GVHD
|
7.4%
2/27
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.
|
|
Gastrointestinal disorders
Colitis
|
7.4%
2/27
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.
|
|
Metabolism and nutrition disorders
Dehydration
|
11.1%
3/27
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.
|
|
Gastrointestinal disorders
Diarrhea
|
22.2%
6/27
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.
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
77.8%
21/27
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.
|
|
Gastrointestinal disorders
Heartburn
|
7.4%
2/27
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.
|
|
Gastrointestinal disorders
Nausea/Vomitting
|
25.9%
7/27
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.
|
|
Gastrointestinal disorders
Nausea
|
22.2%
6/27
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.
|
|
Gastrointestinal disorders
Mucositis
|
59.3%
16/27
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.
|
|
Investigations
Neutropenia
|
68.4%
13/19
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.
|
|
Skin and subcutaneous tissue disorders
Rash
|
7.4%
2/27
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.
|
|
Investigations
Thrombocytopenia
|
10.5%
2/19
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.
|
|
General disorders
Volume overload
|
7.4%
2/27
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.
|
|
Nervous system disorders
Dizziness
|
5.3%
1/19
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.
|
|
Metabolism and nutrition disorders
Hyponatremia
|
5.3%
1/19
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.
|
|
Blood and lymphatic system disorders
Methemoglobinemia
|
5.3%
1/19
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.
|
|
Nervous system disorders
Peripheral neuropathy
|
10.5%
2/19
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.
|
Additional Information
Dr. Leona A. Holmberg
Fred Hutchinson Cancer Research Center
Phone: 206-667-6447
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place