Trial Outcomes & Findings for Bortezomib and Chemotherapy in Treating Participants With Lymphoid Malignancies Undergoing Stem Cell Transplant (NCT NCT00439556)

Last Updated: 2019-09-10

Results Overview

To determine the maximum tolerated dose(MTD) of velcade and dose limiting toxicity(DLT). A dose limiting toxicity (DLT) was defined as a grade 3-4 neurological toxicity, graft failure, or death due to GvHD. The Commom Terminlogy Criteria for Adverse Events v3.0 was used.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

40 participants

Primary outcome timeframe

From start of treatment to 90 days after the start of treatment

Results posted on

2019-09-10

Participant Flow

Patients enrolled at MD Anderson clinic from February 2007 through May 2011.

Participant milestones

Participant milestones
Measure	Velcade Dose Level 1 BEAM (Carmustine/Etoposide/Cytarabine/Melphalan) + Rituxan + ATG (Thymoglobulin) (MUD pts only) + Velcade 1.0mg/m2 + ALLO SCT	Velcade Dose Level 2 BEAM + Rituxan + ATG(MUD pts only) + Velcade 1.3mg/m2 + ALLO SCT
Overall Study STARTED	36	4
Overall Study COMPLETED	36	3
Overall Study NOT COMPLETED	0	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Velcade Dose Level 1 BEAM (Carmustine/Etoposide/Cytarabine/Melphalan) + Rituxan + ATG (Thymoglobulin) (MUD pts only) + Velcade 1.0mg/m2 + ALLO SCT	Velcade Dose Level 2 BEAM + Rituxan + ATG(MUD pts only) + Velcade 1.3mg/m2 + ALLO SCT	Velcade Dose Level 3 BEAM + Rituxan + ATG(MUD pts only) + Velcade 1.6mg/m2 + ALLO SCT
Overall Study Patient was taken off study for non-comp	0	1	0

Baseline Characteristics

Bortezomib and Chemotherapy in Treating Participants With Lymphoid Malignancies Undergoing Stem Cell Transplant

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Velcade Dose Level 1 n=36 Participants BEAM + Rituxan + ATG(MUD pts only) + Velcade (1-1.3mg/m2) + ALLO SCT	Velcade Dose Level 2 n=3 Participants BEAM + Rituxan + ATG(MUD pts only) + Velcade 1.3mg/m2 + ALLO SCT	Velcade Dose Level 3 BEAM + Rituxan + ATG(MUD pts only) + Velcade 1.6mg/m2 + ALLO SCT	Total n=39 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	36 Participants n=5 Participants	3 Participants n=7 Participants	0 Participants n=5 Participants	39 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	54 years n=5 Participants	58 years n=7 Participants	—	54 years n=4 Participants
Sex: Female, Male Female	8 Participants n=5 Participants	1 Participants n=7 Participants	—	9 Participants n=4 Participants
Sex: Female, Male Male	28 Participants n=5 Participants	2 Participants n=7 Participants	—	30 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	5 Participants n=5 Participants	0 Participants n=7 Participants	—	5 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	4 Participants n=5 Participants	0 Participants n=7 Participants	—	4 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	27 Participants n=5 Participants	3 Participants n=7 Participants	—	30 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=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	—	0 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=4 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants	0 Participants n=7 Participants	—	2 Participants n=4 Participants
Race (NIH/OMB) White	32 Participants n=5 Participants	3 Participants n=7 Participants	—	35 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	—	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	0 Participants n=7 Participants	—	2 Participants n=4 Participants
Region of Enrollment United States	36 participants n=5 Participants	3 participants n=7 Participants	—	39 participants n=4 Participants
Breakdown of Disease by Number of Participants in each Dose Level Large Cell Lymphoma	9 Participants n=5 Participants	2 Participants n=7 Participants	—	11 Participants n=4 Participants
Breakdown of Disease by Number of Participants in each Dose Level CLL	12 Participants n=5 Participants	1 Participants n=7 Participants	—	13 Participants n=4 Participants
Breakdown of Disease by Number of Participants in each Dose Level Folicular Lymphoma	8 Participants n=5 Participants	0 Participants n=7 Participants	—	8 Participants n=4 Participants
Breakdown of Disease by Number of Participants in each Dose Level Mantle Cell Lymphoma	2 Participants n=5 Participants	0 Participants n=7 Participants	—	2 Participants n=4 Participants
Breakdown of Disease by Number of Participants in each Dose Level Marginal Zone Lymphoma	1 Participants n=5 Participants	0 Participants n=7 Participants	—	1 Participants n=4 Participants
Breakdown of Disease by Number of Participants in each Dose Level T-Cell Lymphoma	4 Participants n=5 Participants	0 Participants n=7 Participants	—	4 Participants n=4 Participants

PRIMARY outcome

Timeframe: From start of treatment to 90 days after the start of treatment

Population: Patients up to 70 years of age with any histological subtype of CD20+ lymphoid malignancy or T-Cell lymphoid malignancy who were not eligible for a non-myeloablative transplant.

Outcome measures

Outcome measures
Measure	Treatment (Chemotherapy, Transplant, Filgrastim, Tacrolimus) n=36 Participants BEAM + Rituxan + ATG(MUD pts only) + Velcade (1-1.3mg/m2) + ALLO SCT	Velcade Dose Level 2 n=3 Participants BEAM + Rituxan + ATG(MUD pts only) + Velcade 1.3mg/m2 + ALLO SCT	Velcade Dose Level 3 BEAM + Rituxan + ATG(MUD pts only) + Velcade 1.6mg/m2 + ALLO SCT
Number of Participants With Dose Limiting Toxicity (DLT)	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: At 1 year

Population: Patients up to 70 years of age with any histological subtype of CD20+ lymphoid malignancy or T-Cell lymphoid malignancy who were not eligible for a non-myeloablative transplant.

To determine DFS at 1 year post transplant.

Outcome measures

Outcome measures
Measure	Treatment (Chemotherapy, Transplant, Filgrastim, Tacrolimus) n=36 Participants BEAM + Rituxan + ATG(MUD pts only) + Velcade (1-1.3mg/m2) + ALLO SCT	Velcade Dose Level 2 n=3 Participants BEAM + Rituxan + ATG(MUD pts only) + Velcade 1.3mg/m2 + ALLO SCT	Velcade Dose Level 3 BEAM + Rituxan + ATG(MUD pts only) + Velcade 1.6mg/m2 + ALLO SCT
Disease-free Survival	16 Participants	0 Participants	0 Participants

Adverse Events

Velcade Dose Level 1

Serious events: 6 serious events

Other events: 36 other events

Deaths: 6 deaths

Velcade Dose Level 2

Serious events: 2 serious events

Other events: 3 other events

Deaths: 2 deaths

Gemcitabine Dose Level 3

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Velcade Dose Level 1 n=36 participants at risk BEAM + Rituxan + ATG(MUD pts only) + Velcade 1.0mg/m2 + ALLO SCT	Velcade Dose Level 2 n=3 participants at risk BEAM + Rituxan + ATG(MUD pts only) + Velcade 1.3mg/m2 + ALLO SCT	Gemcitabine Dose Level 3 BEAM + Rituxan + ATG(MUD pts only) + Velcade 1.6mg/m2 + ALLO SCT
Infections and infestations Infection	11.1% 4/36 • Number of events 4 • Up to 100 Days post transplant There were no participants enrolled on Velcade dose level 3	66.7% 2/3 • Number of events 2 • Up to 100 Days post transplant There were no participants enrolled on Velcade dose level 3	— 0/0 • Up to 100 Days post transplant There were no participants enrolled on Velcade dose level 3
General disorders Acute GvHD(graft vs Host Disease)	5.6% 2/36 • Number of events 2 • Up to 100 Days post transplant There were no participants enrolled on Velcade dose level 3	0.00% 0/3 • Up to 100 Days post transplant There were no participants enrolled on Velcade dose level 3	— 0/0 • Up to 100 Days post transplant There were no participants enrolled on Velcade dose level 3

Other adverse events

Additional Information

Dr. Khouri,Issa,M.D. / Stem Cell Transplantation

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	Velcade Dose Level 1 n=36 participants at risk BEAM + Rituxan + ATG(MUD pts only) + Velcade 1.0mg/m2 + ALLO SCT	Velcade Dose Level 2 n=3 participants at risk BEAM + Rituxan + ATG(MUD pts only) + Velcade 1.3mg/m2 + ALLO SCT	Gemcitabine Dose Level 3 BEAM + Rituxan + ATG(MUD pts only) + Velcade 1.6mg/m2 + ALLO SCT
Cardiac disorders Dysrhythmia	11.1% 4/36 • Number of events 4 • Up to 100 Days post transplant There were no participants enrolled on Velcade dose level 3	0.00% 0/3 • Up to 100 Days post transplant There were no participants enrolled on Velcade dose level 3	— 0/0 • Up to 100 Days post transplant There were no participants enrolled on Velcade dose level 3
Cardiac disorders Decreased Cardiac Function	8.3% 3/36 • Number of events 3 • Up to 100 Days post transplant There were no participants enrolled on Velcade dose level 3	0.00% 0/3 • Up to 100 Days post transplant There were no participants enrolled on Velcade dose level 3	— 0/0 • Up to 100 Days post transplant There were no participants enrolled on Velcade dose level 3
Cardiac disorders Hypertension	13.9% 5/36 • Number of events 5 • Up to 100 Days post transplant There were no participants enrolled on Velcade dose level 3	0.00% 0/3 • Up to 100 Days post transplant There were no participants enrolled on Velcade dose level 3	— 0/0 • Up to 100 Days post transplant There were no participants enrolled on Velcade dose level 3
General disorders Fluid Overload	36.1% 13/36 • Number of events 13 • Up to 100 Days post transplant There were no participants enrolled on Velcade dose level 3	100.0% 3/3 • Number of events 3 • Up to 100 Days post transplant There were no participants enrolled on Velcade dose level 3	— 0/0 • Up to 100 Days post transplant There were no participants enrolled on Velcade dose level 3
General disorders Fever	36.1% 13/36 • Number of events 14 • Up to 100 Days post transplant There were no participants enrolled on Velcade dose level 3	0.00% 0/3 • Up to 100 Days post transplant There were no participants enrolled on Velcade dose level 3	— 0/0 • Up to 100 Days post transplant There were no participants enrolled on Velcade dose level 3
Gastrointestinal disorders Diarrhea	63.9% 23/36 • Number of events 23 • Up to 100 Days post transplant There were no participants enrolled on Velcade dose level 3	100.0% 3/3 • Number of events 3 • Up to 100 Days post transplant There were no participants enrolled on Velcade dose level 3	— 0/0 • Up to 100 Days post transplant There were no participants enrolled on Velcade dose level 3
Gastrointestinal disorders Mucositis	33.3% 12/36 • Number of events 12 • Up to 100 Days post transplant There were no participants enrolled on Velcade dose level 3	66.7% 2/3 • Number of events 2 • Up to 100 Days post transplant There were no participants enrolled on Velcade dose level 3	— 0/0 • Up to 100 Days post transplant There were no participants enrolled on Velcade dose level 3
Gastrointestinal disorders Nausea	86.1% 31/36 • Number of events 31 • Up to 100 Days post transplant There were no participants enrolled on Velcade dose level 3	100.0% 3/3 • Number of events 3 • Up to 100 Days post transplant There were no participants enrolled on Velcade dose level 3	— 0/0 • Up to 100 Days post transplant There were no participants enrolled on Velcade dose level 3
Renal and urinary disorders Elevated Creatinine	8.3% 3/36 • Number of events 3 • Up to 100 Days post transplant There were no participants enrolled on Velcade dose level 3	66.7% 2/3 • Number of events 2 • Up to 100 Days post transplant There were no participants enrolled on Velcade dose level 3	— 0/0 • Up to 100 Days post transplant There were no participants enrolled on Velcade dose level 3
Renal and urinary disorders Hemorrhagic Cystitis	2.8% 1/36 • Number of events 1 • Up to 100 Days post transplant There were no participants enrolled on Velcade dose level 3	33.3% 1/3 • Number of events 1 • Up to 100 Days post transplant There were no participants enrolled on Velcade dose level 3	— 0/0 • Up to 100 Days post transplant There were no participants enrolled on Velcade dose level 3
Hepatobiliary disorders Transaminitis	13.9% 5/36 • Number of events 5 • Up to 100 Days post transplant There were no participants enrolled on Velcade dose level 3	0.00% 0/3 • Up to 100 Days post transplant There were no participants enrolled on Velcade dose level 3	— 0/0 • Up to 100 Days post transplant There were no participants enrolled on Velcade dose level 3
Infections and infestations Infection	75.0% 27/36 • Number of events 56 • Up to 100 Days post transplant There were no participants enrolled on Velcade dose level 3	100.0% 3/3 • Number of events 5 • Up to 100 Days post transplant There were no participants enrolled on Velcade dose level 3	— 0/0 • Up to 100 Days post transplant There were no participants enrolled on Velcade dose level 3
Infections and infestations Neutropenic Fever	52.8% 19/36 • Number of events 19 • Up to 100 Days post transplant There were no participants enrolled on Velcade dose level 3	0.00% 0/3 • Up to 100 Days post transplant There were no participants enrolled on Velcade dose level 3	— 0/0 • Up to 100 Days post transplant There were no participants enrolled on Velcade dose level 3
Respiratory, thoracic and mediastinal disorders SOB (Shortness of breath)	13.9% 5/36 • Number of events 5 • Up to 100 Days post transplant There were no participants enrolled on Velcade dose level 3	0.00% 0/3 • Up to 100 Days post transplant There were no participants enrolled on Velcade dose level 3	— 0/0 • Up to 100 Days post transplant There were no participants enrolled on Velcade dose level 3
General disorders Acute GvHD	66.7% 24/36 • Number of events 41 • Up to 100 Days post transplant There were no participants enrolled on Velcade dose level 3	33.3% 1/3 • Number of events 1 • Up to 100 Days post transplant There were no participants enrolled on Velcade dose level 3	— 0/0 • Up to 100 Days post transplant There were no participants enrolled on Velcade dose level 3
General disorders Chronic GvHD	19.4% 7/36 • Number of events 9 • Up to 100 Days post transplant There were no participants enrolled on Velcade dose level 3	66.7% 2/3 • Number of events 2 • Up to 100 Days post transplant There were no participants enrolled on Velcade dose level 3	— 0/0 • Up to 100 Days post transplant There were no participants enrolled on Velcade dose level 3