Brentuximab Vedotin After Donor Stem Cell Transplant in Treating Patients With Hematologic Malignancies

This study has been withdrawn prior to enrollment.
Sponsor:
Collaborators:
Seattle Genetics, Inc.
Information provided by (Responsible Party):
Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier:
NCT01620229
First received: June 13, 2012
Last updated: April 17, 2014
Last verified: April 2014
  Purpose

This phase I/II trial studies the side effects and best way to give brentuximab vedotin and to see how well it works after donor stem cell transplant in treating patients with hematologic malignancies. Monoclonal antibodies, such as brentuximab vedotin, can block cancer growth in different ways. Some block the ability of cancer to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Monoclonal antibodies may kill cancer cells that are left after donor stem cell transplant.


Condition Intervention Phase
Hematopoietic/Lymphoid Cancer
Drug: brentuximab vedotin
Other: laboratory biomarker analysis
Other: pharmacological study
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Maintenance Therapy With Brentuximab Vedotin (SGN-35) After Allogeneic Hematopoietic Cell Transplantation for Hodgkin Lymphoma and CD30+ Hematologic Malignancies

Resource links provided by NLM:


Further study details as provided by Fred Hutchinson Cancer Research Center:

Primary Outcome Measures:
  • Incidence of durable hematopoietic engraftment defined as the achievement of > 50% donor CD3+ cell chimerism [ Time Frame: At day 84 after HCT ] [ Designated as safety issue: No ]
    Evaluated according to the allogeneic transplant protocol on which patients are co-enrolled, or according to institutional standard practice if no monitoring scheme is specified in the transplant protocol.


Secondary Outcome Measures:
  • Rates of relapse [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Response criteria will be based on the 2007 revisions to the International Working Group criteria for malignant lymphoma.

  • Non-relapse mortality [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Response criteria will be based on the 2007 revisions to the International Working Group criteria for malignant lymphoma.

  • Incidence of acute GVHD [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
  • Peak grade of acute GVHD [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
  • Incidence of chronic GVHD [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
  • Severity of chronic GVHD [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
  • Incidence of adverse events related to brentuximab vedotin, graded according to National Cancer Institute Common Toxicity Criteria version 4 [ Time Frame: Up to 30 days after completion of study treatment ] [ Designated as safety issue: Yes ]

Enrollment: 0
Study Start Date: June 2013
Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (brentuximab vedotin)
Patients receive brentuximab vedotin IV on day 1. Treatment repeats every 21 days for up to 16 courses in the absence of disease progression or unacceptable toxicity.
Drug: brentuximab vedotin
Given IV
Other Names:
  • Adcetris
  • anti-CD30 ADC SGN-35
  • anti-CD30 antibody-drug conjugate SGN-35
  • antibody-drug conjugate SGN-35
  • SGN-35
Other: laboratory biomarker analysis
Correlative studies
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To determine the incidence of durable donor hematopoietic engraftment (defined by donor T-cell chimerism > 50% at day +84 after hematopoietic cell transplantation [HCT]) after allogeneic HCT and post-transplant brentuximab vedotin.

SECONDARY OBJECTIVES:

I. Rates of complete and partial response; incidence of acute graft-versus-host disease (GVHD) grades II-IV and chronic GVHD; overall and progression-free survival; rates of serious adverse events associated with brentuximab vedotin.

OUTLINE:

Patients receive brentuximab vedotin intravenously (IV) on day 1. Treatment repeats every 21 days for up to 16 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 5 years.

  Eligibility

Ages Eligible for Study:   12 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must have a cluster of differentiation (CD)30+ malignancy, with CD30 positivity demonstrated either at time of original diagnosis or at any subsequent time point
  • Patients must have undergone allogeneic HCT from a related or unrelated donor; acceptable donors include:

    • Related donors: genotypically or phenotypically identical by serological typing for human leukocyte antigen (HLA)-A, -B, -C, and at the allele level for -DRB1 and -DQB1
    • Unrelated donors: Fred Hutchinson Cancer Research Center (FHCRC) matching allowed will be grade 1.0 to 2.1: matched for HLA-A, -B, -C, -DRB1 and -DQB1 by high-resolution typing
    • For all donors, a single allele disparity will be allowed for HLA-A, -B, or -C as defined by high-resolution typing
    • Patients with HLA-haploidentical donors are not eligible
  • Patients must have documented post-transplant donor CD3+ chimerism of > 50% in sorted peripheral-blood CD3+ cells
  • Patients must be at least 28 days out from allogeneic HCT at the time of enrollment; in general, patients should be no more than 60 days out from allogeneic HCT at time of enrollment; however, patients more than 60 days out from allogeneic HCT may be considered for enrollment in discussion with the protocol investigator (Dr. Maloney)
  • Patients must be enrolled on an FHCRC non-myeloablative allogeneic transplant protocol (not standard treatment plan); for eligibility purposes, "non-myeloablative" is defined here as conditioning therapy consisting of =< 4 Gy total body irradiation, with or without fludarabine
  • Patients with prior exposure to brentuximab vedotin are eligible for enrollment on this trial, regardless of previous disease response
  • Women of childbearing age and men with female partners of childbearing age must be willing and able to use an effective method of contraception during the study and for at least 30 days after the last study dose of brentuximab vedotin
  • Patients must be able to give informed consent

Exclusion Criteria:

  • Patients who are seropositive for human immunodeficiency virus (HIV)
  • Women who are pregnant or breast-feeding
  • Patients with moderate to severe peripheral neuropathy (grade 2 or higher); patients with a history of moderate/severe peripheral neuropathy may be enrolled if their neuropathy improves to =< grade 1 at the time of enrollment
  • Patients with significant hepatic dysfunction, as manifested by a total serum bilirubin > 4.0 g/dL; or clinical evidence of decompensated hepatic failure; or clinical evidence of decompensated portal hypertension
  • Patients with an absolute neutrophil count of < 1,000 cells/mm^3
  • Patients with Eastern Cooperative Oncology Group (ECOG) performance status of > 2
  • Patients with a serum creatinine > 3.0 mg/dL
  • Patients with known hypersensitivity to brentuximab vedotin or any excipient contained in the drug formulation
  • Patients currently receiving treatment with other systemic anti-neoplastic or investigational agents targeting their CD30+ hematologic malignancy
  • Patients with active and uncontrolled infection not responding to appropriate treatment should be discussed with the study investigator (Dr. Maloney) before enrollment
  • Patients who have received donor lymphocyte infusion for low donor chimerism or pending graft rejection are not eligible
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01620229

Locations
United States, Washington
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington, United States, 98109
Sponsors and Collaborators
Fred Hutchinson Cancer Research Center
Seattle Genetics, Inc.
Investigators
Principal Investigator: David Maloney Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
  More Information

No publications provided

Responsible Party: Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier: NCT01620229     History of Changes
Other Study ID Numbers: 2560.00, NCI-2012-00924, 2560.00, P30CA015704, P01CA018029
Study First Received: June 13, 2012
Last Updated: April 17, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Hematologic Neoplasms
Neoplasms by Site
Neoplasms
Hematologic Diseases
Antibodies, Monoclonal
Immunoconjugates
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 22, 2014