Trial Outcomes & Findings for Brentuximab Vedotin in High-Risk CD30+ Lymphoma Post Allogeneic Stem Cell Transplantation (AlloSCT) (NCT NCT02169505)

NCT ID: NCT02169505

Last Updated: 2019-11-27

Results Overview

Safety is defined by no more than two secondary graft failures within 6 months of transplant (Day 0), based on an observed graft failure rate of \<10% using standard of care treatment. If at any time more than two of these events are observed during the specified time frame, the study will be stopped and no further patients will be accrued.

• Recruitment status: TERMINATED
• Study phase: PHASE2
• Target enrollment: 2 participants
• Primary outcome timeframe: An average of 12 months
• Results posted on: 2019-11-27

Participant Flow

Participants who have had an Allogeneic and Haploidentical Stem Cell Transplantation in High Risk CD30+ Lymphoma (Hodgkin Lymphoma and ALCL)

Participant milestones

Measure	Safety and Efficacy of Brentuximab Vedotin Maintenance After A Study the safety of Brentuximab in patients with HL or ALCL who have had an allo or haplo stem cell transplant. Also learn if drug prevents the disease from coming back.
Overall Study STARTED	2
Overall Study COMPLETED	1
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Measure	Safety and Efficacy of Brentuximab Vedotin Maintenance After A Study the safety of Brentuximab in patients with HL or ALCL who have had an allo or haplo stem cell transplant. Also learn if drug prevents the disease from coming back.
Overall Study Withdrawal by Subject	1

Baseline Characteristics

Brentuximab Vedotin in High-Risk CD30+ Lymphoma Post Allogeneic Stem Cell Transplantation (AlloSCT)

Baseline characteristics by cohort

Measure	Safety and Efficacy of Brentuximab Vedotin Maintenance After A n=2 Participants Study the safety of Brentuximab in patients with HL or ALCL who have had an allo or haplo stem cell transplant. Also learn if drug prevents the disease from coming back.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	2 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants
Sex: Female, Male Male	2 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	0 Participants n=5 Participants
Race (NIH/OMB) White	2 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	2 Participants n=5 Participants

PRIMARY outcome

Timeframe: An average of 12 months

Safety is defined by no more than two secondary graft failures within 6 months of transplant (Day 0), based on an observed graft failure rate of <10% using standard of care treatment. If at any time more than two of these events are observed during the specified time frame, the study will be stopped and no further patients will be accrued.

Outcome measures

Measure

1.2 mg/kg for C1-2 Then 1.8mg/kg for C3-6 n=1 Participants Dose will be reduced from 1.8 mg/kg to 1.2 mg/kg or from 1.2 mg/kg to 1 mg/kg or from 1 mg/kg to stop treatment if: 1. Neutropenia grade 3-4 unresponsive to G-CSF or grade 4 thrombocytopenia are observed. 2. Peripheral neuropathy, new or worsening grade 2 or 3. Withhold treatment until improvement or return to grade 1 or baseline; then resume with a dose reduction. Dose will be reduced to 1 mg/kg if: 1. Creatinine clearance \< 30 cc/min as defined by MDRD method from NKDEP. http://nkdep.nih.gov/lab-evaluation/gfr/estimating.shtml 2. Hepatic impairment defined as bilirubin \> 2 mg/dL. If the patient develops grade 3-4 neutropenia unresponsive to G-CSF: Hold until resolution to grade \</= 1 and restart at lower dose.

Number of Participants With Secondary Graft Failure

0 participants

SECONDARY outcome

Timeframe: an average of 12 months

The most common grade > 3 side effects on Brentuximab.

Outcome measures

Measure

1.2 mg/kg for C1-2 Then 1.8mg/kg for C3-6 n=1 Participants Dose will be reduced from 1.8 mg/kg to 1.2 mg/kg or from 1.2 mg/kg to 1 mg/kg or from 1 mg/kg to stop treatment if: 1. Neutropenia grade 3-4 unresponsive to G-CSF or grade 4 thrombocytopenia are observed. 2. Peripheral neuropathy, new or worsening grade 2 or 3. Withhold treatment until improvement or return to grade 1 or baseline; then resume with a dose reduction. Dose will be reduced to 1 mg/kg if: 1. Creatinine clearance \< 30 cc/min as defined by MDRD method from NKDEP. http://nkdep.nih.gov/lab-evaluation/gfr/estimating.shtml 2. Hepatic impairment defined as bilirubin \> 2 mg/dL. If the patient develops grade 3-4 neutropenia unresponsive to G-CSF: Hold until resolution to grade \</= 1 and restart at lower dose.

Number of Participants With Hematologic Toxicity

0 Participants

SECONDARY outcome

Timeframe: an average of 12 months

Evaluate the safety of brentuximab early after allogeneic stem cell transplant and haploidentical allogeneic transplantant and observe if there is a decrease in the risk of relapse.

Outcome measures

Measure

1.2 mg/kg for C1-2 Then 1.8mg/kg for C3-6 n=1 Participants Dose will be reduced from 1.8 mg/kg to 1.2 mg/kg or from 1.2 mg/kg to 1 mg/kg or from 1 mg/kg to stop treatment if: 1. Neutropenia grade 3-4 unresponsive to G-CSF or grade 4 thrombocytopenia are observed. 2. Peripheral neuropathy, new or worsening grade 2 or 3. Withhold treatment until improvement or return to grade 1 or baseline; then resume with a dose reduction. Dose will be reduced to 1 mg/kg if: 1. Creatinine clearance \< 30 cc/min as defined by MDRD method from NKDEP. http://nkdep.nih.gov/lab-evaluation/gfr/estimating.shtml 2. Hepatic impairment defined as bilirubin \> 2 mg/dL. If the patient develops grade 3-4 neutropenia unresponsive to G-CSF: Hold until resolution to grade \</= 1 and restart at lower dose.

Number of Participants With Relapse

0 Participants

SECONDARY outcome

Timeframe: an average of 12 months

Evaluate the CMV in blood

Outcome measures

Measure

1.2 mg/kg for C1-2 Then 1.8mg/kg for C3-6 n=1 Participants Dose will be reduced from 1.8 mg/kg to 1.2 mg/kg or from 1.2 mg/kg to 1 mg/kg or from 1 mg/kg to stop treatment if: 1. Neutropenia grade 3-4 unresponsive to G-CSF or grade 4 thrombocytopenia are observed. 2. Peripheral neuropathy, new or worsening grade 2 or 3. Withhold treatment until improvement or return to grade 1 or baseline; then resume with a dose reduction. Dose will be reduced to 1 mg/kg if: 1. Creatinine clearance \< 30 cc/min as defined by MDRD method from NKDEP. http://nkdep.nih.gov/lab-evaluation/gfr/estimating.shtml 2. Hepatic impairment defined as bilirubin \> 2 mg/dL. If the patient develops grade 3-4 neutropenia unresponsive to G-CSF: Hold until resolution to grade \</= 1 and restart at lower dose.

Number of Participants With Incidence of Cytomegalovirus (CMV) Reactivation and/or CMV Disease.

0 Participants

SECONDARY outcome

Timeframe: an average of 12 months

The tissue and serum in participants were measured by the GVHD

Outcome measures

Measure

1.2 mg/kg for C1-2 Then 1.8mg/kg for C3-6 n=1 Participants Dose will be reduced from 1.8 mg/kg to 1.2 mg/kg or from 1.2 mg/kg to 1 mg/kg or from 1 mg/kg to stop treatment if: 1. Neutropenia grade 3-4 unresponsive to G-CSF or grade 4 thrombocytopenia are observed. 2. Peripheral neuropathy, new or worsening grade 2 or 3. Withhold treatment until improvement or return to grade 1 or baseline; then resume with a dose reduction. Dose will be reduced to 1 mg/kg if: 1. Creatinine clearance \< 30 cc/min as defined by MDRD method from NKDEP. http://nkdep.nih.gov/lab-evaluation/gfr/estimating.shtml 2. Hepatic impairment defined as bilirubin \> 2 mg/dL. If the patient develops grade 3-4 neutropenia unresponsive to G-CSF: Hold until resolution to grade \</= 1 and restart at lower dose.

Number of Participants With Acute Graft-versus-host Disease (GVHD).

0 Participants

SECONDARY outcome

Timeframe: an average of 12 months

We will perform on peripheral blood for mononuclear cells (PBMC) and serum collected from participants at baseline (prior to initiation of brentuximab therapy) and on days 1, 3, and 5 after initiation of brentuximab and every 21 days thereafter to assess the effect on T cell subsets and their effector function as well as other immune subsets.

Outcome measures

Measure

1.2 mg/kg for C1-2 Then 1.8mg/kg for C3-6 n=1 Participants Dose will be reduced from 1.8 mg/kg to 1.2 mg/kg or from 1.2 mg/kg to 1 mg/kg or from 1 mg/kg to stop treatment if: 1. Neutropenia grade 3-4 unresponsive to G-CSF or grade 4 thrombocytopenia are observed. 2. Peripheral neuropathy, new or worsening grade 2 or 3. Withhold treatment until improvement or return to grade 1 or baseline; then resume with a dose reduction. Dose will be reduced to 1 mg/kg if: 1. Creatinine clearance \< 30 cc/min as defined by MDRD method from NKDEP. http://nkdep.nih.gov/lab-evaluation/gfr/estimating.shtml 2. Hepatic impairment defined as bilirubin \> 2 mg/dL. If the patient develops grade 3-4 neutropenia unresponsive to G-CSF: Hold until resolution to grade \</= 1 and restart at lower dose.

Number of Participants With Central and Effector Cell Effects

0 Participants

SECONDARY outcome

Timeframe: an average of 12 months

Immunological correlative studies on peripheral blood mononuclear cells (PBMC) and serum will be collected from participants at baseline (prior to initiation of brentuximab therapy) and on days 1, 3, and 5 after initiation of brentuximab and every 21 days thereafter to assess the effect on T cell subsets and their effector function as well as CD30 levels.

Outcome measures

Measure

1.2 mg/kg for C1-2 Then 1.8mg/kg for C3-6 n=1 Participants Dose will be reduced from 1.8 mg/kg to 1.2 mg/kg or from 1.2 mg/kg to 1 mg/kg or from 1 mg/kg to stop treatment if: 1. Neutropenia grade 3-4 unresponsive to G-CSF or grade 4 thrombocytopenia are observed. 2. Peripheral neuropathy, new or worsening grade 2 or 3. Withhold treatment until improvement or return to grade 1 or baseline; then resume with a dose reduction. Dose will be reduced to 1 mg/kg if: 1. Creatinine clearance \< 30 cc/min as defined by MDRD method from NKDEP. http://nkdep.nih.gov/lab-evaluation/gfr/estimating.shtml 2. Hepatic impairment defined as bilirubin \> 2 mg/dL. If the patient develops grade 3-4 neutropenia unresponsive to G-CSF: Hold until resolution to grade \</= 1 and restart at lower dose.

Number of Participants With Change in Serum CD30 Levels After Brentuximab Administration

0 Participants

SECONDARY outcome

Timeframe: an average of 12 months

Population: Participant one had a progression free survival and overall survival.

The Kaplan-Meier (1958) survival curves were used to estimate the overall survival and progression-free survival. Cox proportional hazards regression analysis was used to model the association between overall survival and progression-free survival and disease and demographic covariates of interest.

Outcome measures

Measure	1.2 mg/kg for C1-2 Then 1.8mg/kg for C3-6 n=1 Participants Dose will be reduced from 1.8 mg/kg to 1.2 mg/kg or from 1.2 mg/kg to 1 mg/kg or from 1 mg/kg to stop treatment if: 1. Neutropenia grade 3-4 unresponsive to G-CSF or grade 4 thrombocytopenia are observed. 2. Peripheral neuropathy, new or worsening grade 2 or 3. Withhold treatment until improvement or return to grade 1 or baseline; then resume with a dose reduction. Dose will be reduced to 1 mg/kg if: 1. Creatinine clearance \< 30 cc/min as defined by MDRD method from NKDEP. http://nkdep.nih.gov/lab-evaluation/gfr/estimating.shtml 2. Hepatic impairment defined as bilirubin \> 2 mg/dL. If the patient develops grade 3-4 neutropenia unresponsive to G-CSF: Hold until resolution to grade \</= 1 and restart at lower dose.
Number of Participants With Progression-Free Survival and Overall Survival on Brentuximab Maintenance Progression-free survival	1 Participants
Number of Participants With Progression-Free Survival and Overall Survival on Brentuximab Maintenance Overall	1 Participants

Adverse Events

Treatment Arm

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Treatment Arm n=2 participants at risk 1.2 mg/kg for C1-2 then 1.8mg/kg for C3-6
Blood and lymphatic system disorders Decreased ANC	100.0% 2/2 • 1 year
Blood and lymphatic system disorders Dcreased WBC	50.0% 1/2 • 1 year
Blood and lymphatic system disorders Decreased PLT	50.0% 1/2 • 1 year
Skin and subcutaneous tissue disorders Skin Rash	50.0% 1/2 • 1 year

Additional Information

Ahmed,Sairah,MD / Stem Cell Transplantation

UT MD Anderson Cancer Center

Phone: 713-792-7734

Email: sahmed3@mdanderson.org

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place