Trial Outcomes & Findings for Aza-SAHA-GBM With AutoSCT for Refractory Lymphoma (NCT NCT01983969)
NCT ID: NCT01983969
Last Updated: 2020-01-27
Results Overview
Maximum tolerated dose (MTD) of azacitidine based on DLT was defined as any Grade 4 nonhematologic and noninfectious toxicity or any grade 3 mucositis or skin toxicity lasting \> 3 days at peak severity. For dose finding, the continunal reassessment method was used with a target DLT probability per cohort of 25%. Azacitidine doses were chosen adaptively for sucessive cohorts with a minimum size of 2 patients. Toxicity scoring followed the National Cancer Institute Common Toxicity Criteria, version 3.
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
61 participants
Primary outcome timeframe
Enrollment up to day 30 post transplant for each dosing cohort
Results posted on
2020-01-27
Participant Flow
Patients enrolled at MD Anderson Clinic between November 2013 and May 2015.
Participant milestones
| Measure |
Azacitidine Dose Level 1
Azacitidine 15 mg/m2 IV for 10 days+Vorinostat 1000 mg PO for 10 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)
|
Azacitidine Dose Level 2
Azacitidine 25mg/m2 IV for 10 days+Vorinostat 1000 mg PO for 10 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)
|
Azacitidine Dose Level 3
Azacitidine 35 mg/m2 IV for 10 days+Vorinostat 1000 mg PO for 10 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
|
37
|
19
|
5
|
|
Overall Study
COMPLETED
|
37
|
18
|
5
|
|
Overall Study
NOT COMPLETED
|
0
|
1
|
0
|
Reasons for withdrawal
| Measure |
Azacitidine Dose Level 1
Azacitidine 15 mg/m2 IV for 10 days+Vorinostat 1000 mg PO for 10 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)
|
Azacitidine Dose Level 2
Azacitidine 25mg/m2 IV for 10 days+Vorinostat 1000 mg PO for 10 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)
|
Azacitidine Dose Level 3
Azacitidine 35 mg/m2 IV for 10 days+Vorinostat 1000 mg PO for 10 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
Disease Progression
|
0
|
1
|
0
|
Baseline Characteristics
Aza-SAHA-GBM With AutoSCT for Refractory Lymphoma
Baseline characteristics by cohort
| Measure |
Azacitidine Dose Level 1
n=37 Participants
Azacitidine 15 mg/m2 IV for 10 days+Vorinostat 1000 mg PO for 10 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 SCT
|
Azacitidine Dose Level 2
n=18 Participants
Azacitidine 25 mg/m2 IV for 10 days+Vorinostat 1000 mg PO for 10 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 SCT
|
Azacitidine Dose Level 3
n=5 Participants
Azacitidine 35 mg/m2 IV for 10 days+Vorinostat 1000 mg PO for 10 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 SCT
|
Total
n=60 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
36 Participants
n=5 Participants
|
18 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
59 Participants
n=4 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Age, Continuous
|
42.5 years
n=5 Participants
|
41 years
n=7 Participants
|
38 years
n=5 Participants
|
41 years
n=4 Participants
|
|
Sex: Female, Male
Female
|
14 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
25 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
23 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
35 Participants
n=4 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Black or African American
|
5 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
9 Participants
n=4 Participants
|
|
Race (NIH/OMB)
White
|
20 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
33 Participants
n=4 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
12 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
16 Participants
n=4 Participants
|
|
Region of Enrollment
United States
|
37 participants
n=5 Participants
|
18 participants
n=7 Participants
|
5 participants
n=5 Participants
|
60 participants
n=4 Participants
|
|
Overall Study Group
Disease-DLBCL
|
18 participants
n=5 Participants
|
7 participants
n=7 Participants
|
1 participants
n=5 Participants
|
26 participants
n=4 Participants
|
|
Overall Study Group
Disease-Hodgkin lymphoma
|
12 participants
n=5 Participants
|
6 participants
n=7 Participants
|
3 participants
n=5 Participants
|
21 participants
n=4 Participants
|
|
Overall Study Group
Disease-T-cell lymphoma
|
5 participants
n=5 Participants
|
3 participants
n=7 Participants
|
0 participants
n=5 Participants
|
8 participants
n=4 Participants
|
|
Overall Study Group
Disease-Other B-cell lymphoma
|
2 participants
n=5 Participants
|
2 participants
n=7 Participants
|
1 participants
n=5 Participants
|
5 participants
n=4 Participants
|
PRIMARY outcome
Timeframe: Enrollment up to day 30 post transplant for each dosing cohortMaximum tolerated dose (MTD) of azacitidine based on DLT was defined as any Grade 4 nonhematologic and noninfectious toxicity or any grade 3 mucositis or skin toxicity lasting \> 3 days at peak severity. For dose finding, the continunal reassessment method was used with a target DLT probability per cohort of 25%. Azacitidine doses were chosen adaptively for sucessive cohorts with a minimum size of 2 patients. Toxicity scoring followed the National Cancer Institute Common Toxicity Criteria, version 3.
Outcome measures
| Measure |
Other B-cell Lymphoma
Other B-cell lymphoma (Follicular lymphoma and Mantle cell lymphoma) who received the following: Azacitidine 15 mg/m2-35 mg/m2 IV for 10 days+Vorinostat 1000 mg PO for 10 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 SCT
|
Azacitidine Dose Level 1
n=37 Participants
Azacitidine 15 mg/m2 IV for 10 days+Vorinostat 1000 mg PO for 10 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 SCT
|
Azacitidine Dose Level 2
n=18 Participants
Azacitidine 25 mg/m2 IV for 10 days+Vorinostat 1000 mg PO for 10 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 SCT
|
Azacitidine Dose Level 3
n=5 Participants
Azacitidine 35 mg/m2 IV for 10 days+Vorinostat 1000 mg PO for 10 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 SCT
|
|---|---|---|---|---|
|
Frequency of DLT
|
—
|
16 Dose-limiting toxicities
|
28 Dose-limiting toxicities
|
40 Dose-limiting toxicities
|
PRIMARY outcome
Timeframe: Enrollment up to 100 days post transplant.EFS is defined as the time from transplantation to either relapse, second tumors, or death, whichever occurred first, or last contact. EFS was analzyed by the individual disease groups rather than the cohort dose levels.
Outcome measures
| Measure |
Other B-cell Lymphoma
n=5 Participants
Other B-cell lymphoma (Follicular lymphoma and Mantle cell lymphoma) who received the following: Azacitidine 15 mg/m2-35 mg/m2 IV for 10 days+Vorinostat 1000 mg PO for 10 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 SCT
|
Azacitidine Dose Level 1
n=26 Participants
Azacitidine 15 mg/m2 IV for 10 days+Vorinostat 1000 mg PO for 10 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 SCT
|
Azacitidine Dose Level 2
n=21 Participants
Azacitidine 25 mg/m2 IV for 10 days+Vorinostat 1000 mg PO for 10 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 SCT
|
Azacitidine Dose Level 3
n=8 Participants
Azacitidine 35 mg/m2 IV for 10 days+Vorinostat 1000 mg PO for 10 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 SCT
|
|---|---|---|---|---|
|
Participants With Event-free Survival (EFS)
|
5 Participants
|
17 Participants
|
16 Participants
|
7 Participants
|
Adverse Events
Azacitidine Dose Level 1
Serious events: 0 serious events
Other events: 37 other events
Deaths: 1 deaths
Azacitidine Dose Level 2
Serious events: 0 serious events
Other events: 18 other events
Deaths: 0 deaths
Azacitidine Dose Level 3
Serious events: 0 serious events
Other events: 5 other events
Deaths: 1 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Azacitidine Dose Level 1
n=37 participants at risk
Azacitidine 15 mg/m2 IV for 10 days+Vorinostat 1000 mg PO for 10 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 SCT
|
Azacitidine Dose Level 2
n=18 participants at risk
Azacitidine 25 mg/m2 IV for 10 days+Vorinostat 1000 mg PO for 10 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 SCT
|
Azacitidine Dose Level 3
n=5 participants at risk
Azacitidine 35 mg/m2 IV for 10 days+Vorinostat 1000 mg PO for 10 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 SCT
|
|---|---|---|---|
|
Cardiac disorders
Hypertension
|
8.1%
3/37 • Number of events 3 • Up to 100 Days post autologous transplant.
|
16.7%
3/18 • Number of events 3 • Up to 100 Days post autologous transplant.
|
0.00%
0/5 • Up to 100 Days post autologous transplant.
|
|
Cardiac disorders
DVT
|
2.7%
1/37 • Number of events 1 • Up to 100 Days post autologous transplant.
|
11.1%
2/18 • Number of events 2 • Up to 100 Days post autologous transplant.
|
0.00%
0/5 • Up to 100 Days post autologous transplant.
|
|
General disorders
Fever
|
10.8%
4/37 • Number of events 4 • Up to 100 Days post autologous transplant.
|
11.1%
2/18 • Number of events 2 • Up to 100 Days post autologous transplant.
|
0.00%
0/5 • Up to 100 Days post autologous transplant.
|
|
General disorders
Fluid Overload
|
56.8%
21/37 • Number of events 21 • Up to 100 Days post autologous transplant.
|
50.0%
9/18 • Number of events 9 • Up to 100 Days post autologous transplant.
|
40.0%
2/5 • Number of events 2 • Up to 100 Days post autologous transplant.
|
|
Gastrointestinal disorders
Diarrhea
|
70.3%
26/37 • Number of events 26 • Up to 100 Days post autologous transplant.
|
66.7%
12/18 • Number of events 12 • Up to 100 Days post autologous transplant.
|
40.0%
2/5 • Number of events 2 • Up to 100 Days post autologous transplant.
|
|
Gastrointestinal disorders
Mucositis
|
91.9%
34/37 • Number of events 34 • Up to 100 Days post autologous transplant.
|
94.4%
17/18 • Number of events 17 • Up to 100 Days post autologous transplant.
|
100.0%
5/5 • Number of events 5 • Up to 100 Days post autologous transplant.
|
|
Gastrointestinal disorders
Nausea
|
91.9%
34/37 • Number of events 34 • Up to 100 Days post autologous transplant.
|
83.3%
15/18 • Number of events 15 • Up to 100 Days post autologous transplant.
|
100.0%
5/5 • Number of events 5 • Up to 100 Days post autologous transplant.
|
|
Renal and urinary disorders
Elevated Creatinine
|
18.9%
7/37 • Number of events 7 • Up to 100 Days post autologous transplant.
|
5.6%
1/18 • Number of events 1 • Up to 100 Days post autologous transplant.
|
40.0%
2/5 • Number of events 2 • Up to 100 Days post autologous transplant.
|
|
Renal and urinary disorders
Hemorrhagic Cystitis
|
2.7%
1/37 • Number of events 1 • Up to 100 Days post autologous transplant.
|
11.1%
2/18 • Number of events 2 • Up to 100 Days post autologous transplant.
|
0.00%
0/5 • Up to 100 Days post autologous transplant.
|
|
Hepatobiliary disorders
Transaminitis
|
64.9%
24/37 • Number of events 27 • Up to 100 Days post autologous transplant.
|
72.2%
13/18 • Number of events 15 • Up to 100 Days post autologous transplant.
|
20.0%
1/5 • Number of events 1 • Up to 100 Days post autologous transplant.
|
|
Hepatobiliary disorders
Elevated Bilirubin
|
40.5%
15/37 • Number of events 15 • Up to 100 Days post autologous transplant.
|
50.0%
9/18 • Number of events 9 • Up to 100 Days post autologous transplant.
|
60.0%
3/5 • Number of events 3 • Up to 100 Days post autologous transplant.
|
|
Infections and infestations
Infection
|
37.8%
14/37 • Number of events 24 • Up to 100 Days post autologous transplant.
|
38.9%
7/18 • Number of events 9 • Up to 100 Days post autologous transplant.
|
80.0%
4/5 • Number of events 4 • Up to 100 Days post autologous transplant.
|
|
Infections and infestations
Neutropenic Fever
|
100.0%
37/37 • Number of events 38 • Up to 100 Days post autologous transplant.
|
88.9%
16/18 • Number of events 16 • Up to 100 Days post autologous transplant.
|
100.0%
5/5 • Number of events 5 • Up to 100 Days post autologous transplant.
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
5.4%
2/37 • Number of events 2 • Up to 100 Days post autologous transplant.
|
22.2%
4/18 • Number of events 4 • Up to 100 Days post autologous transplant.
|
20.0%
1/5 • Number of events 1 • Up to 100 Days post autologous transplant.
|
|
Skin and subcutaneous tissue disorders
Skin Rash
|
56.8%
21/37 • Number of events 21 • Up to 100 Days post autologous transplant.
|
33.3%
6/18 • Number of events 6 • Up to 100 Days post autologous transplant.
|
60.0%
3/5 • Number of events 3 • Up to 100 Days post autologous transplant.
|
Additional Information
Nieto, Yago / Stem Cell Transplantation and Cellular Therapy
UT MD Anderson Cancer Center
Phone: 713-792-8750
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place