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

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

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

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=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	1 Participants n=157 Participants
Age, Categorical Between 18 and 65 years	36 Participants n=99 Participants	18 Participants n=107 Participants	5 Participants n=206 Participants	59 Participants n=157 Participants
Age, Categorical >=65 years	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=157 Participants
Age, Continuous	42.5 years n=99 Participants	41 years n=107 Participants	38 years n=206 Participants	41 years n=157 Participants
Sex: Female, Male Female	14 Participants n=99 Participants	8 Participants n=107 Participants	3 Participants n=206 Participants	25 Participants n=157 Participants
Sex: Female, Male Male	23 Participants n=99 Participants	10 Participants n=107 Participants	2 Participants n=206 Participants	35 Participants n=157 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=157 Participants
Race (NIH/OMB) Asian	0 Participants n=99 Participants	2 Participants n=107 Participants	0 Participants n=206 Participants	2 Participants n=157 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=157 Participants
Race (NIH/OMB) Black or African American	5 Participants n=99 Participants	4 Participants n=107 Participants	0 Participants n=206 Participants	9 Participants n=157 Participants
Race (NIH/OMB) White	20 Participants n=99 Participants	9 Participants n=107 Participants	4 Participants n=206 Participants	33 Participants n=157 Participants
Race (NIH/OMB) More than one race	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=157 Participants
Race (NIH/OMB) Unknown or Not Reported	12 Participants n=99 Participants	3 Participants n=107 Participants	1 Participants n=206 Participants	16 Participants n=157 Participants
Region of Enrollment United States	37 participants n=99 Participants	18 participants n=107 Participants	5 participants n=206 Participants	60 participants n=157 Participants
Overall Study Group Disease-DLBCL	18 participants n=99 Participants	7 participants n=107 Participants	1 participants n=206 Participants	26 participants n=157 Participants
Overall Study Group Disease-Hodgkin lymphoma	12 participants n=99 Participants	6 participants n=107 Participants	3 participants n=206 Participants	21 participants n=157 Participants
Overall Study Group Disease-T-cell lymphoma	5 participants n=99 Participants	3 participants n=107 Participants	0 participants n=206 Participants	8 participants n=157 Participants
Overall Study Group Disease-Other B-cell lymphoma	2 participants n=99 Participants	2 participants n=107 Participants	1 participants n=206 Participants	5 participants n=157 Participants

PRIMARY outcome

Timeframe: Enrollment up to day 30 post transplant for each dosing cohort

Outcome measures

Outcome measures
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	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
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

Outcome measures
Measure	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	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
Participants With Event-free Survival (EFS)	17 Participants	16 Participants	7 Participants	5 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

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

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.