Trial Outcomes & Findings for Lenalidomide Combined With Vorinostat/Gemcitabine/Busulfan/Melphalan With Autologous Stem-Cell Transplantation in Diffuse Large B-Cell Lymphoma of the ABC Subtype (NCT NCT02589145)
NCT ID: NCT02589145
Last Updated: 2019-12-13
Results Overview
Established the maximum tolerated dose (MTD) of lenalidomide combined with vorinostat/gemcitabine/busulfan/melphalan with autologous stem-cell transplant ASCT). Maximum tolerated dose (MTD) of lenalidomide based on DLT was defined as any Grade 4 or 5 nonhematologic, noninfectious toxicity or any grade 3 mucositis or skin toxicity lasting \> 5 days at their peak severity. Lenalidomide doses were chosen adaptively for successive cohorts with a minimum size of 2 patients. Toxicity scoring followed the National Cancer Institute Common Toxicity Criteria, version 4.
Recruitment status
TERMINATED
Study phase
PHASE1/PHASE2
Target enrollment
8 participants
Primary outcome timeframe
Enrollment up to day 30 post transplant for each dosing cohort
Results posted on
2019-12-13
Participant Flow
Patients enrolled at MD Anderson Clinic starting on August 22, 2016.
Participant milestones
| Measure |
Lenalidomide Dose Level 1
Lenalidomide 50 mg PO for 8 days+Vorinostat 1000 mg PO for 8 days+ Busulfan (adjusted PK dosing) IV for 4 days+Gemcitabine 2775 mg/m2 IV for 2 days+Melphalan 60 mg/m2 IV for 2 days +/- Rituximab 375 mg/m2 IV for 1 day (for CD20 positive tumors)+ Auto Stem Cell Transplant (SCT)
|
Lenalidomide Dose Level 2
Lenalidomide 75 mg PO for 8 days+Vorinostat 1000 mg PO for 8 days+ Busulfan (adjusted PK dosing) IV for 4 days+Gemcitabine 2775 mg/m2 IV for 2 days+Melphalan 60 mg/m2 IV for 2 days +/- Rituximab 375 mg/m2 IV for 1 day (for CD20 positive tumors)+ Auto Stem Cell Transplant (SCT)
|
Lenalidomide Dose Level 3
Lenalidomide 100 mg PO for 8 days+Vorinostat 1000 mg PO for 8 days+ Busulfan (adjusted PK dosing) IV for 4 days+Gemcitabine 2775 mg/m2 IV for 2 days+Melphalan 60 mg/m2 IV for 2 days +/- Rituximab 375 mg/m2 IV for 1 day (for CD20 positive tumors)+ Auto Stem Cell Transplant (SCT)
|
|---|---|---|---|
|
Overall Study
STARTED
|
4
|
2
|
2
|
|
Overall Study
COMPLETED
|
4
|
2
|
2
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Patients age 15-65 with ABC (determined by immunohistochemistry using the Hans algorithm) Diffuse Large B-cell Lymphoma (DLBCL) with primary refractory disease..
Baseline characteristics by cohort
| Measure |
Total
n=8 Participants
Total of all reporting groups
|
Lenalidomide Dose Level 1
n=4 Participants
Lenalidomide 50 mg PO for 8 days+Vorinostat 1000 mg PO for 8 days+ Busulfan (adjusted PK dosing) IV for 4 days+Gemcitabine 2775 mg/m2 IV for 2 days+Melphalan 60 mg/m2 IV for 2 days +/- Rituximab 375 mg/m2 IV for 1 day (for CD20 positive tumors)+ Auto Stem Cell Transplant (SCT)
|
Lenalidomide Dose Level 2
n=2 Participants
Lenalidomide 75 mg PO for 8 days+Vorinostat 1000 mg PO for 8 days+ Busulfan (adjusted PK dosing) IV for 4 days+Gemcitabine 2775 mg/m2 IV for 2 days+Melphalan 60 mg/m2 IV for 2 days +/- Rituximab 375 mg/m2 IV for 1 day (for CD20 positive tumors)+ Auto Stem Cell Transplant (SCT)
|
Lenalidomide Dose Level 3
n=2 Participants
Lenalidomide 100 mg PO for 8 days+Vorinostat 1000 mg PO for 8 days+ Busulfan (adjusted PK dosing) IV for 4 days+Gemcitabine 2775 mg/m2 IV for 2 days+Melphalan 60 mg/m2 IV for 2 days +/- Rituximab 375 mg/m2 IV for 1 day (for CD20 positive tumors)+ Auto Stem Cell Transplant (SCT)
|
|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=8 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=2 Participants
|
0 Participants
n=2 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
8 Participants
n=8 Participants
|
4 Participants
n=4 Participants
|
2 Participants
n=2 Participants
|
2 Participants
n=2 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=8 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=2 Participants
|
0 Participants
n=2 Participants
|
|
Age, Continuous
|
56.5 Years
n=8 Participants
|
55.5 Years
n=4 Participants
|
42.5 Years
n=2 Participants
|
58 Years
n=2 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=8 Participants
|
1 Participants
n=4 Participants
|
0 Participants
n=2 Participants
|
1 Participants
n=2 Participants
|
|
Sex: Female, Male
Male
|
6 Participants
n=8 Participants
|
3 Participants
n=4 Participants
|
2 Participants
n=2 Participants
|
1 Participants
n=2 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
3 Participants
n=8 Participants
|
2 Participants
n=4 Participants
|
0 Participants
n=2 Participants
|
1 Participants
n=2 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
5 Participants
n=8 Participants
|
2 Participants
n=4 Participants
|
2 Participants
n=2 Participants
|
1 Participants
n=2 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=8 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=2 Participants
|
0 Participants
n=2 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=8 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=2 Participants
|
0 Participants
n=2 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=8 Participants
|
1 Participants
n=4 Participants
|
0 Participants
n=2 Participants
|
0 Participants
n=2 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=8 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=2 Participants
|
0 Participants
n=2 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=8 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=2 Participants
|
0 Participants
n=2 Participants
|
|
Race (NIH/OMB)
White
|
6 Participants
n=8 Participants
|
2 Participants
n=4 Participants
|
2 Participants
n=2 Participants
|
2 Participants
n=2 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=8 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=2 Participants
|
0 Participants
n=2 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=8 Participants
|
1 Participants
n=4 Participants
|
0 Participants
n=2 Participants
|
0 Participants
n=2 Participants
|
|
Region of Enrollment
United States
|
8 participants
n=8 Participants
|
4 participants
n=4 Participants
|
2 participants
n=2 Participants
|
2 participants
n=2 Participants
|
|
Disease Status
Complete Remission
|
6 Participants
n=8 Participants • Patients age 15-65 with ABC (determined by immunohistochemistry using the Hans algorithm) Diffuse Large B-cell Lymphoma (DLBCL) with primary refractory disease..
|
3 Participants
n=4 Participants • Patients age 15-65 with ABC (determined by immunohistochemistry using the Hans algorithm) Diffuse Large B-cell Lymphoma (DLBCL) with primary refractory disease..
|
2 Participants
n=2 Participants • Patients age 15-65 with ABC (determined by immunohistochemistry using the Hans algorithm) Diffuse Large B-cell Lymphoma (DLBCL) with primary refractory disease..
|
1 Participants
n=2 Participants • Patients age 15-65 with ABC (determined by immunohistochemistry using the Hans algorithm) Diffuse Large B-cell Lymphoma (DLBCL) with primary refractory disease..
|
|
Disease Status
Partial Remission
|
2 Participants
n=2 Participants • Patients age 15-65 with ABC (determined by immunohistochemistry using the Hans algorithm) Diffuse Large B-cell Lymphoma (DLBCL) with primary refractory disease..
|
1 Participants
n=1 Participants • Patients age 15-65 with ABC (determined by immunohistochemistry using the Hans algorithm) Diffuse Large B-cell Lymphoma (DLBCL) with primary refractory disease..
|
—
|
1 Participants
n=1 Participants • Patients age 15-65 with ABC (determined by immunohistochemistry using the Hans algorithm) Diffuse Large B-cell Lymphoma (DLBCL) with primary refractory disease..
|
PRIMARY outcome
Timeframe: Enrollment up to day 30 post transplant for each dosing cohortPopulation: Due to low accrual, MTD could not be determined for this outcome.
Established the maximum tolerated dose (MTD) of lenalidomide combined with vorinostat/gemcitabine/busulfan/melphalan with autologous stem-cell transplant ASCT). Maximum tolerated dose (MTD) of lenalidomide based on DLT was defined as any Grade 4 or 5 nonhematologic, noninfectious toxicity or any grade 3 mucositis or skin toxicity lasting \> 5 days at their peak severity. Lenalidomide doses were chosen adaptively for successive cohorts with a minimum size of 2 patients. Toxicity scoring followed the National Cancer Institute Common Toxicity Criteria, version 4.
Outcome measures
Outcome data not reported
PRIMARY outcome
Timeframe: Up to 2 years post transplantPopulation: Due to low accrual, EFS could not be determined for this outcome.
Determined the 2-year event-free survival (EFS)
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Up to 2 years post transplantPopulation: Due to low accrual, OS could not be determined for this outcome.
Assessed the 2-year overall survival (OS)
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Up to 2 years post transplantPopulation: Due to low accrual, CR rate could not be determined for this outcome.
Determined complete remission (CR) rate
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Up to 2 years post transplantPopulation: Due to low accrual, the ORR could not be determined for this outcome.
Determined overall remission rate (ORR) rate
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Up to 2 years post transplantPopulation: Due to low accrual, the Toxicity profile could not be determined for this outcome.
Determined the toxicity profile
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Up to 2 years post transplantPopulation: Due to low accrual, the pharmacodynamic studies could not be determined for this outcome.
Evaluated IRF4, SPIB, STAT1, p-STAT1, CARD11, I-kappa-Kinase-beta and p-I-kappa-Kinase-beta in PBMNC pre- and post-treatment (at baseline and on day -1).
Outcome measures
Outcome data not reported
Adverse Events
Lenalidomide Dose Level 1
Serious events: 1 serious events
Other events: 4 other events
Deaths: 1 deaths
Lenalidomide Dose Level 2
Serious events: 0 serious events
Other events: 2 other events
Deaths: 1 deaths
Lenalidomide Dose Level 3
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Lenalidomide Dose Level 1
n=4 participants at risk
Lenalidomide 50 mg PO for 8 days+Vorinostat 1000 mg PO for 8 days+ Busulfan (adjusted PK dosing) IV for 4 days+Gemcitabine 2775 mg/m2 IV for 2 days+Melphalan 60 mg/m2 IV for 2 days +/- Rituximab 375 mg/m2 IV for 1 day (for CD20 positive tumors)+ Auto Stem Cell Transplant (SCT)
|
Lenalidomide Dose Level 2
n=2 participants at risk
Lenalidomide 75 mg PO for 8 days+Vorinostat 1000 mg PO for 8 days+ Busulfan (adjusted PK dosing) IV for 4 days+Gemcitabine 2775 mg/m2 IV for 2 days+Melphalan 60 mg/m2 IV for 2 days +/- Rituximab 375 mg/m2 IV for 1 day (for CD20 positive tumors)+ Auto Stem Cell Transplant (SCT)
|
Lenalidomide Dose Level 3
n=2 participants at risk
Lenalidomide 100 mg PO for 8 days+Vorinostat 1000 mg PO for 8 days+ Busulfan (adjusted PK dosing) IV for 4 days+Gemcitabine 2775 mg/m2 IV for 2 days+Melphalan 60 mg/m2 IV for 2 days +/- Rituximab 375 mg/m2 IV for 1 day (for CD20 positive tumors)+ Auto Stem Cell Transplant (SCT)
|
|---|---|---|---|
|
Gastrointestinal disorders
Ileus
|
25.0%
1/4 • Up to 100 Days post autologous transplant
|
0.00%
0/2 • Up to 100 Days post autologous transplant
|
0.00%
0/2 • Up to 100 Days post autologous transplant
|
|
Gastrointestinal disorders
Mucositis
|
25.0%
1/4 • Up to 100 Days post autologous transplant
|
0.00%
0/2 • Up to 100 Days post autologous transplant
|
0.00%
0/2 • Up to 100 Days post autologous transplant
|
|
Hepatobiliary disorders
Elevated Bilirubin
|
25.0%
1/4 • Up to 100 Days post autologous transplant
|
0.00%
0/2 • Up to 100 Days post autologous transplant
|
0.00%
0/2 • Up to 100 Days post autologous transplant
|
|
Metabolism and nutrition disorders
Hypernatremia
|
25.0%
1/4 • Up to 100 Days post autologous transplant
|
0.00%
0/2 • Up to 100 Days post autologous transplant
|
0.00%
0/2 • Up to 100 Days post autologous transplant
|
Other adverse events
| Measure |
Lenalidomide Dose Level 1
n=4 participants at risk
Lenalidomide 50 mg PO for 8 days+Vorinostat 1000 mg PO for 8 days+ Busulfan (adjusted PK dosing) IV for 4 days+Gemcitabine 2775 mg/m2 IV for 2 days+Melphalan 60 mg/m2 IV for 2 days +/- Rituximab 375 mg/m2 IV for 1 day (for CD20 positive tumors)+ Auto Stem Cell Transplant (SCT)
|
Lenalidomide Dose Level 2
n=2 participants at risk
Lenalidomide 75 mg PO for 8 days+Vorinostat 1000 mg PO for 8 days+ Busulfan (adjusted PK dosing) IV for 4 days+Gemcitabine 2775 mg/m2 IV for 2 days+Melphalan 60 mg/m2 IV for 2 days +/- Rituximab 375 mg/m2 IV for 1 day (for CD20 positive tumors)+ Auto Stem Cell Transplant (SCT)
|
Lenalidomide Dose Level 3
n=2 participants at risk
Lenalidomide 100 mg PO for 8 days+Vorinostat 1000 mg PO for 8 days+ Busulfan (adjusted PK dosing) IV for 4 days+Gemcitabine 2775 mg/m2 IV for 2 days+Melphalan 60 mg/m2 IV for 2 days +/- Rituximab 375 mg/m2 IV for 1 day (for CD20 positive tumors)+ Auto Stem Cell Transplant (SCT)
|
|---|---|---|---|
|
General disorders
Fluid Overload
|
75.0%
3/4 • Number of events 3 • Up to 100 Days post autologous transplant
|
50.0%
1/2 • Number of events 1 • Up to 100 Days post autologous transplant
|
0.00%
0/2 • Up to 100 Days post autologous transplant
|
|
Gastrointestinal disorders
Diarrhea
|
50.0%
2/4 • Number of events 2 • Up to 100 Days post autologous transplant
|
0.00%
0/2 • Up to 100 Days post autologous transplant
|
50.0%
1/2 • Number of events 1 • Up to 100 Days post autologous transplant
|
|
Gastrointestinal disorders
Mucositis
|
75.0%
3/4 • Number of events 3 • Up to 100 Days post autologous transplant
|
100.0%
2/2 • Number of events 2 • Up to 100 Days post autologous transplant
|
100.0%
2/2 • Number of events 2 • Up to 100 Days post autologous transplant
|
|
Gastrointestinal disorders
Nausea
|
75.0%
3/4 • Number of events 3 • Up to 100 Days post autologous transplant
|
100.0%
2/2 • Number of events 2 • Up to 100 Days post autologous transplant
|
100.0%
2/2 • Number of events 2 • Up to 100 Days post autologous transplant
|
|
Skin and subcutaneous tissue disorders
Rash
|
50.0%
2/4 • Number of events 2 • Up to 100 Days post autologous transplant
|
0.00%
0/2 • Up to 100 Days post autologous transplant
|
0.00%
0/2 • Up to 100 Days post autologous transplant
|
|
Infections and infestations
Neutropenic Fever
|
100.0%
4/4 • Number of events 4 • Up to 100 Days post autologous transplant
|
100.0%
2/2 • Number of events 2 • Up to 100 Days post autologous transplant
|
100.0%
2/2 • Number of events 2 • Up to 100 Days post autologous transplant
|
|
Hepatobiliary disorders
Transaminitis
|
50.0%
2/4 • Number of events 2 • Up to 100 Days post autologous transplant
|
100.0%
2/2 • Number of events 3 • Up to 100 Days post autologous transplant
|
50.0%
1/2 • Number of events 2 • Up to 100 Days post autologous transplant
|
|
Hepatobiliary disorders
Elevated Bilirubin
|
100.0%
4/4 • Number of events 4 • Up to 100 Days post autologous transplant
|
50.0%
1/2 • Number of events 1 • Up to 100 Days post autologous transplant
|
0.00%
0/2 • Up to 100 Days post autologous transplant
|
|
Gastrointestinal disorders
Ileus
|
25.0%
1/4 • Number of events 1 • Up to 100 Days post autologous transplant
|
0.00%
0/2 • Up to 100 Days post autologous transplant
|
0.00%
0/2 • Up to 100 Days post autologous transplant
|
|
Metabolism and nutrition disorders
Hypernatremia
|
25.0%
1/4 • Number of events 1 • Up to 100 Days post autologous transplant
|
0.00%
0/2 • Up to 100 Days post autologous transplant
|
0.00%
0/2 • Up to 100 Days post autologous transplant
|
|
Skin and subcutaneous tissue disorders
Skin other Desquamation/Burn
|
25.0%
1/4 • Number of events 1 • Up to 100 Days post autologous transplant
|
50.0%
1/2 • Number of events 1 • Up to 100 Days post autologous transplant
|
50.0%
1/2 • Number of events 1 • Up to 100 Days post autologous transplant
|
|
Infections and infestations
Infection
|
25.0%
1/4 • Number of events 2 • Up to 100 Days post autologous transplant
|
50.0%
1/2 • Number of events 2 • Up to 100 Days post autologous transplant
|
100.0%
2/2 • Number of events 2 • Up to 100 Days post autologous transplant
|
Additional Information
Dr. Yago Nieto/Professor, Stem Cell Transplantation
UT MD Anderson Cancer Center
Phone: 713-792-2466
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place