Trial record 1 of 1 for:    NCT01700751
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Brentuximab Vedotin Prevention of (GVHD) After Unrelated Allogeneic Stem Cell Transplantation

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by Washington University School of Medicine
Sponsor:
Information provided by (Responsible Party):
Washington University School of Medicine
ClinicalTrials.gov Identifier:
NCT01700751
First received: September 18, 2012
Last updated: August 25, 2014
Last verified: August 2014
  Purpose

This pilot clinical trial studies the safety and maximum tolerated dose of brentuximab vedotin when given with tacrolimus and methotrexate after unrelated allogeneic donor stem cell transplant in patients with acute myeloid leukemia, acute lymphoblastic leukemia, or myelodysplastic syndromes. The addition of brentuximab vedotin to tacrolimus and methotrexate may result in a significant reduction of graft versus host disease in these patients.


Condition Intervention Phase
Leukemia, Acute Myeloid
Leukemia, Lymphoblastic,Acute
Myelodysplastic Syndromes
Drug: brentuximab vedotin
Phase 0

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Pilot Study of Brentuximab Vedotin in the Prevention of Graft-Versus-Host Disease (GVHD) After Unrelated Allogeneic Stem Cell Transplantation

Resource links provided by NLM:


Further study details as provided by Washington University School of Medicine:

Primary Outcome Measures:
  • MTD of brentuximab vedotin when administered with a GVHD prophylaxis regimen [ Time Frame: 37 days ] [ Designated as safety issue: Yes ]

    Defined as the dose level immediately below the dose level at which 2 patients of a cohort (of 2 to 6 patients) experience dose-limiting toxicity; Hematologic DLT is defined as ANC < 500/mm3 for three consecutive days beyond Day +21 that was determined by the investigator to be likely related to brentuximab vedotin.

    Non-hematologic DLT is defined as any grade 3 or higher non-hematologic toxicity that was determined by the investigator to be possibly, probably, or definitely related to brentuximab vedotin, with the following specific exceptions:

    • Grade 3 or 4 nausea, vomiting, diarrhea, mucositis, or fatigue thought to be associated with conditioning regimens
    • Grade 3 rash will only be considered a DLT for patients who have received two weeks of supportive care treatment with no improvement.


Secondary Outcome Measures:
  • Safety and tolerability of brentuximab vedotin when administered with a GVHD prophylaxis regimen [ Time Frame: 100 days ] [ Designated as safety issue: Yes ]
    Toxicities described and graded using CTCAE version 4.0; described by patient, type, and grade for each dose level; summarized by counts and percentage of patients in the corresponding categories

  • Rate of acute GVHD [ Time Frame: 100 days ] [ Designated as safety issue: No ]
    Proportion of all subjects who experience symptoms consistent with grade 2-4 acute GVHD; using the standard grading system adapted from the Glucksberg clinical stage and grade of acute GVHD

  • Rate of chronic GVHD [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Proportion of all subjects who experience symptoms consistent with chronic GVHD; assessment will begin after Day 100 using the NIH consensus criteria for diagnosis and staging of chronic GVHD

  • Progression-free survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Duration from the time of transplant to time of first progression, death, relapse after complete response, or the date the patient was last known to be in remission; estimated with Kaplan-Meier methods.

  • Overall survival. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Duration from the time of transplant to death or last follow-up; estimated with Kaplan-Meier methods.

  • 1-year non-relapse mortality rate [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Defined as the percentage of patients dying from etiologies other than disease relapse; estimated with Kaplan-Meier methods.

  • 2-year non-relapse mortality rate [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Defined as the percentage of patients dying from etiologies other than disease relapse; estimated with Kaplan-Meier methods.

  • 1-year disease relapse rate [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Defined as the percentage of patients who have disease relapse; estimated with Kaplan-Meier methods.

  • 2-year disease relapse rate [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Defined as the percentage of patients who have disease relapse; estimated with Kaplan-Meier methods.


Estimated Enrollment: 36
Study Start Date: February 2013
Estimated Study Completion Date: August 2016
Estimated Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dose Level 0 (starting dose)
brentuximab vedotin 0.3mg/kg, given IV on Days 7, 28, 49 & 70
Drug: brentuximab vedotin
Other Name: Adcetris
Experimental: Dose Level 1
brentuximab vedotin 0.6mg/kg, given IV on Days 7, 28, 49 & 70
Drug: brentuximab vedotin
Other Name: Adcetris
Experimental: Dose Level 2
brentuximab vedotin 1.2mg/kg, given IV on Days 7, 28, 49 & 70
Drug: brentuximab vedotin
Other Name: Adcetris
Experimental: Dose Level 3
brentuximab vedotin 1.8mg/kg, given IV on Days 7, 28, 49 & 70
Drug: brentuximab vedotin
Other Name: Adcetris
No Intervention: Control Dose Level
The first 3 patients will not receive brentuximab vedotin.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patient must be scheduled to undergo stem cell transplantation for one of the following diagnoses:

    • acute myeloid leukemia (AML) in CR1 (first complete remission, CR or CRi) or CR2 (second complete remission, CR or CRi),
    • acute lymphoblastic leukemia (ALL) in CR1 or CR2 (CR or CRi)
    • myelodysplastic syndrome (MDS) without progression to AML.
    • Chronic myelogenous leukemia (CML)
    • Non-Hodgkin's lymphoma (NHL) or Hodgkin's disease (HD)
    • Chronic lymphocytic leukemia (CLL)
    • Multiple myeloma (MM)
  • Patients must be the recipient of unrelated donor peripheral blood stem cell products. Mismatches at both antigen and allele level will be eligible. Match must be 6 or 7 out of 8 loci (HLA A, B, C, and DRB1).
  • Patient must receive any one of the following conditioning regimens: total body radiation (single or fractionated dose)/cyclophosphamide, busulfan/ cyclophosphamide, or fludarabine/busulfan/lymphocyte immune globulin (ATGAM/thymo).
  • Patient must be ≥ 18 years and ≤ 70 years of age.
  • Patient must have an ECOG performance status ≤ 2 or Karnofsky performance scale ≥ 60%
  • Patient must have CD34+ stem cells ≥ 2x106/kg (actual body weight of the recipient) available for transplantation.
  • Patient must have appropriate organ function as defined below (this criterion should be met on screening and on the day of the first dose of brentuximab vedotin (as assessed prior to dosing)):

    • Total bilirubin ≤ 2.0 x IULN
    • AST(SGOT)/ALT(SGPT) ≤ 3.0 x IULN
    • Serum creatinine ≤ 2.0 x IULN
    • Estimated Creatinine Clearance > 30 ml/min
    • Cardiac ejection fraction > 40%
    • DLCO/VA > 40%
  • Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.
  • Patient must be able to understand and willing to sign an IRB approved written informed consent document.

Exclusion Criteria:

  • Patient must not have had prior exposure to brentuximab vedotin.
  • Patient must not have a history of other malignancy that has not been in remission for at least 3 years, with the exception of basal non-melanoma skin cancer which were treated with local resection only or intraepithelial lesions or carcinoma in situ of the cervix or prostate that has been curatively treated.
  • Patient must not be receiving any other investigational agents.
  • Patient must not have active CNS involvement.
  • Patient must not have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to brentuximab vedotin or other agents used in the study.
  • Patients must not have had previous radiation therapy to the mediastinum or lungs.
  • Patient must not have an uncontrolled inter-current illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, active pulmonary diseases, or psychiatric illness/social situations that would limit compliance with study requirements (this criterion should be met on screening and on the day of but prior to first dose of brentuximab vedotin).
  • Patient must not be pregnant and/or breastfeeding.
  • Patient must not be known to be HIV-positive on combination antiretroviral therapies.
  • Patient must not have had a previous allogeneic or syngeneic transplant. Prior autologous transplant is allowed.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01700751

Contacts
Contact: John DiPersio, M.D., Ph.D. 314-454-8304 jdipersi@dom.wustl.edu

Locations
United States, Missouri
Washington University School of Medicine Recruiting
St. Louis, Missouri, United States, 63110
Contact: John DiPersio, M.D., Ph.D.    314-454-8304    jdipersi@dom.wustl.edu   
Sub-Investigator: Camille Abboud, M.D.         
Sub-Investigator: Amanda Cashen, M.D.         
Sub-Investigator: Mark Schroeder, M.D.         
Sub-Investigator: Keith Stockerl-Goldstein, M.D.         
Sub-Investigator: Geoffrey Uy, M.D.         
Sub-Investigator: Ravi Vij, M.D.         
Sub-Investigator: Peter Westervelt, M.D., Ph.D.         
Sub-Investigator: Tzu-Fei Wang, M.D.         
Sponsors and Collaborators
Washington University School of Medicine
Investigators
Principal Investigator: John DiPersio, M.D., Ph.D. Washington University School of Medicine
  More Information

Additional Information:
No publications provided

Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT01700751     History of Changes
Other Study ID Numbers: 201211047
Study First Received: September 18, 2012
Last Updated: August 25, 2014
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Additional relevant MeSH terms:
Myelodysplastic Syndromes
Preleukemia
Leukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Myeloid, Acute
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Neoplasms
Neoplasms by Histologic Type
Leukemia, Lymphoid
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, Myeloid
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 16, 2014