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

Lymphoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02169505
• Other study ID #: 2013-0351
• Secondary ID: NCI-2014-01593
• Status: Terminated
• Phase: Phase 2
• Start date: May 22, 2015
• Est. completion date: August 14, 2017

Study information

• Verified date: November 2019
• Source: M.D. Anderson Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 2
• Est. completion date: August 14, 2017
• Est. primary completion date: August 14, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Lymphoma

Intervention

Drug:
• Brentuximab 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.

Locations

Country	Name	City	State
United States	University of Texas MD Anderson Cancer Center	Houston	Texas

Sponsors (1)

Lead Sponsor	Collaborator
M.D. Anderson Cancer Center

Country where clinical trial is conducted

United States, 

Outcome

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

External Links

•   University of Texas MD Anderson Cancer Center Website