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

Safety and Efficacy of Brentuximab Vedotin Maintenance After Allogeneic and Haploidentical Stem Cell Transplantation in High Risk CD30+ Lymphoma (Hodgkin Lymphoma and ALCL)

Status

Terminated

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02169505

Enrollment

Registered

2014-06-23

Start date

2015-05-22

Completion date

2017-08-14

Last updated

2019-11-27

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Lymphoma

Keywords

Lymphoma, Hodgkin lymphoma, HL, CD30 positive Hodgkin Lymphoma, Anaplastic large cell lymphoma, ALCL, Allogeneic Stem Cell Transplantation, ASCT, Graft-versus-host disease, GVHD, Brentuximab Vedotin, SGN-35, Adcetris

Brief summary

The goal of this clinical research study is to study the safety of ADCETRISTM (brentuximab vedotin) in patients with Hodgkin lymphoma or ALCL who have had an allogeneic or haploidentical stem cell transplant. Another goal of this study is to learn if brentuximab vedotin can help to prevent the disease from coming back.

Detailed description

Study Drug Administration: If you agree to take part in this study, about 35-60 days after the transplant, you will receive brentuximab vedotin by vein over about 30 minutes on Day 1 of each 21-day study cycle. You may receive up to 6 cycles of brentuximab vedotin. At Cycles 3 and beyond, you will receive a higher dose of the study drug than you received during Cycles 1 and 2. Study Visits: About 5 days before Day 1 of Cycle 1: * You will have a physical exam. As part of the physical exam, you will be checked for graft-versus-host disease (GVHD -- when transplanted donor tissue attacks the tissues of the recipient's body). You may have an additional blood draw to check for GVHD as part of your standard of care. * Blood (about 2 tablespoons) will be drawn for routine tests and to check how the transplant has taken. * Blood (about 2 teaspoons each time) will be drawn before and after your dose of study drug to check the immune system. On Days 3 and 5 of Cycle 1, blood (about 2 teaspoons) will be drawn to check the immune system. About 5 days before Day 1 of Cycles 2-6: * You will have a physical exam. * Blood (about 2 tablespoons) will be drawn for routine tests and to check the immune system. If your doctor thinks it is needed, you may have a skin biopsy or endoscopy to check for GVHD and/or graft failure. You will sign a separate consent form that explains the procedures and risks. Length of Study: You will be taken off study 1 year after the transplant. You will no longer be able to take the study drug if the disease gets worse, if intolerable side effects occur, if you develop an infection (such as cytomegalovirus \[CMV\] that does not respond to treatment), or if you are unable to follow study directions. Your participation on the study will be over after the follow-up visits. Follow-Up Visits: About 1, 3, 6, and 12 months after the transplant, you will have follow-up visits as part of your standard of care after your transplant. At these visits: * You will have a physical exam * Blood (about 4 tablespoons) will be drawn for routine tests, to learn how the transplant has taken, and to check the status of the disease. * You will have a computed tomography (CT) scan to check the status of the disease. * You will have a bone marrow biopsy and aspiration to check the status of the disease and for cytogenetic testing. To collect a bone marrow biopsy/aspirate, an area of the hip or other site is numbed with anesthetic, and a small amount of bone marrow and bone is withdrawn through a large needle. Cytogenetic testing looks at how genetic changes to cells may affect how the disease may react to the study drug. This is an investigational study. Brentuximab vedotin is FDA approved and commercially available for the treatment of Hodgkin lymphoma and ALCL. It is investigational to give brentuximab vedotin at an earlier time after a transplant. Up to 20 participants will be enrolled in this study. All will take part at MD Anderson.

Interventions

DRUGBrentuximab Vedotin

Starting dose: 1.2 mg/kg by vein on Day 1 for the first 2, 21 day cycles. Dose increased to 1.8 mg/kg by vein after the second cycle for all subsequent cycles.

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 65 Years

Healthy volunteers

Inclusion criteria

1. Patients with CD30 positive Hodgkin Lymphoma (HL) or anaplastic large cell lymphoma (ALCL) that have undergone allogeneic or haploidentical SCT in the past 60 days (matched related or matched unrelated donors only). 2. Age 18 to 65 years. 3. Performance status: Zubrod 0-1 or Karnofsky 80-100. 4. Serum creatinine \< 1.5 mg/dL or creatinine clearance greater than or equal to 40 cc/min as defined by MDRD method from National Kidney Disease Education Program (NKDEP). 5. Serum direct bilirubin \< 1.5 mg/dL (unless Gilbert's syndrome). 6. SGPT \< 200 IU/L unless related to patient's malignancy. 7. Evidence of neutrophil and platelet engraftment, defined as platelet count equal or greater than 50,000 mm3 independent of platelet transfusion and ANC equal or greater to 1000 without growth factor support for at least 5 days. 8. Patients with previous exposure to brentuximab pre-transplant are eligible for the study.

Exclusion criteria

1. Pregnancy or breast-feeding (women of childbearing potential, any female who has experienced menarche and who has not undergone surgical sterilization or is post-menopausal with a positive serum pregnancy test. 2. Presence of steroid-refractory acute graft-versus-host disease (GVHD). 3. Patients that underwent allogeneic transplantation as a treatment of graft failure. 4. Dual refractory CMV reactivation to foscarnet and ganciclovir or evidence of CMV disease.

Design outcomes

Primary

Measure	Time frame	Description
Number of Participants With Secondary Graft Failure	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.

Secondary

Measure	Time frame	Description
Number of Participants With Relapse	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.
Number of Participants With Incidence of Cytomegalovirus (CMV) Reactivation and/or CMV Disease.	an average of 12 months	Evaluate the CMV in blood
Number of Participants With Acute Graft-versus-host Disease (GVHD).	an average of 12 months	The tissue and serum in participants were measured by the GVHD
Number of Participants With Hematologic Toxicity	an average of 12 months	The most common grade \> 3 side effects on Brentuximab.
Number of Participants With Change in Serum CD30 Levels After Brentuximab Administration	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.
Number of Participants With Progression-Free Survival and Overall Survival on Brentuximab Maintenance	an average of 12 months	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.
Number of Participants With Central and Effector Cell Effects	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.

Countries

United States

Participant flow

Recruitment details

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

Participants by arm

Arm	Count
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.	2
Total	2

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Withdrawal by Subject	1

Baseline characteristics

Characteristic	Safety and Efficacy of Brentuximab Vedotin Maintenance After A
Age, Categorical <=18 years	0 Participants
Age, Categorical >=65 years	0 Participants
Age, Categorical Between 18 and 65 years	2 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants
Race (NIH/OMB) Asian	0 Participants
Race (NIH/OMB) Black or African American	0 Participants
Race (NIH/OMB) More than one race	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants
Race (NIH/OMB) White	2 Participants
Region of Enrollment United States	2 Participants
Sex: Female, Male Female	0 Participants
Sex: Female, Male Male	2 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	0 / 2
other Total, other adverse events	2 / 2
serious Total, serious adverse events	0 / 2

Outcome results

Primary

Number of Participants With Secondary Graft Failure

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.

Time frame: An average of 12 months

Arm	Measure	Value (NUMBER)
1.2 mg/kg for C1-2 Then 1.8mg/kg for C3-6	Number of Participants With Secondary Graft Failure	0 participants

Secondary