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Brentuximab Vedotin in Treating Patients With Advanced Systemic Mastocytosis or Mast Cell Leukemia

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2015 by Stanford University
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Jason Robert Gotlib, Stanford University
ClinicalTrials.gov Identifier:
NCT01807598
First received: March 5, 2013
Last updated: November 20, 2015
Last verified: November 2015
  Purpose
This pilot clinical trial studies brentuximab vedotin in treating patients with advanced systemic mastocytosis or mast cell leukemia. Monoclonal antibodies, such as brentuximab vedotin, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them

Condition Intervention
Aggressive Systemic Mastocytosis
Mast Cell Leukemia
Systemic Mastocytosis
Drug: brentuximab vedotin

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Study of Brentuximab Vedotin (SGN-35) in CD30-Positive Systemic Mastocytosis With or Without an Associated Hematological Clonal Non-Mast Cell Lineage Disease (AHNMD)

Resource links provided by NLM:


Further study details as provided by Stanford University:

Primary Outcome Measures:
  • Overall response rate per consensus international response criteria (rate of complete or partial remissions or clinical improvement) [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
    Will be estimated and its 95% confidence interval will be provided.


Secondary Outcome Measures:
  • Immunohistochemical expression of CD30 on neoplastic mast cells in core biopsy samples by flow cytometry [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
  • Total symptom score using a modified Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
  • Duration of response [ Time Frame: Time from first onset of confirmed response to the date of first documented and confirmed progression or death, assessed up to 1 year ] [ Designated as safety issue: No ]
    The Kaplan-Meier product-limit method will be used to summarize.

  • Time to response [ Time Frame: Time from start of treatment until the date of onset of a confirmed response, assessed up to 1 year ] [ Designated as safety issue: No ]
    The Kaplan-Meier product-limit method will be used to summarize.

  • Progression-free survival (PFS) [ Time Frame: Time from start of treatment to the date of the first documented and confirmed progression or death or institution of new therapy, assessed up to 1 year ] [ Designated as safety issue: No ]
    The Kaplan-Meier product-limit method will be used to summarize.

  • Type of adverse events measured by National Cancer Institute Common Toxicity Criteria (NCI CTC) version 4.03 [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
  • Quality of life (QOL) score using a modified Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
  • Incidence of adverse events measured by National Cancer Institute Common Toxicity Criteria (NCI CTC) version 4.03 [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
  • Severity of adverse events measured by National Cancer Institute Common Toxicity Criteria (NCI CTC) version 4.03 [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
  • Seriousness of adverse events measured by National Cancer Institute Common Toxicity Criteria (NCI CTC) version 4.03 [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
  • Relatedness of adverse events measured by National Cancer Institute Common Toxicity Criteria (NCI CTC) version 4.03 [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]

Estimated Enrollment: 11
Study Start Date: September 2013
Estimated Study Completion Date: June 2017
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Brentuximab vedotin
Subjects receive a 30-minute IV infusion of brentuximab vedotin once every 21 days for 8 courses, in the absence of disease progression or unacceptable toxicity.
Drug: brentuximab vedotin
Brentuximab vedotin is an antibody with a covalently attached toxin. The antibody portion targets the protein CD30 on the surface of cells, and the toxin acts against those cells.
Other Names:
  • Adcetris
  • anti-CD30 antibody-drug conjugate
  • anti-CD30 ADC
  • SGN-35

Detailed Description:

PRIMARY OBJECTIVES:

I. To evaluate the response rate to SGN-35 (brentuximab vedotin) in patients with tumor necrosis factor receptor superfamily, member 8 (CD30+) advanced systemic mastocytosis (SM) (ASM or mast cell leukemia [MCL] with or without an associated hematological clonal non-mast cell lineage disease [AHNMD]).

SECONDARY OBJECTIVES:

I. To evaluate the tolerability and safety profile of SGN-35 in patients with SM.

II. To evaluate expression of CD30 on neoplastic mast cells before and during therapy with SGN-35.

III. To evaluate changes in mastocytosis related symptom scores and quality of life (QOL) using a modified Myeloproliferative Neoplasm Symptom Assessment Form (MPNSAF).

IV. To evaluate the duration of response (DoR) and time to response (TTR). V. To evaluate progression-free survival (PFS).

OUTLINE:

Patients receive brentuximab vedotin intravenously (IV) over 30 minutes on day 1. Treatment repeats every 21 days for 8 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 6 weeks for 1 year and then every 12 weeks thereafter.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Written informed consent
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-3
  • Life expectancy > 12 weeks
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x upper limit of normal (ULN), if caused by ASM/MCL =< 5 x ULN
  • Serum direct bilirubin =< 1.5 x ULN; if considered related to ASM/MCL =< 3 x ULN
  • Serum creatinine =< 2.0 mg/dL
  • A diagnosis of systemic mastocytosis (SM) per 2008 World Health Organization (WHO) Criteria
  • Neoplastic mast cells must express CD30 by immunohistochemistry or flow cytometry
  • At least one of the eligible organ damage findings as defined by the international consensus response criteria
  • Females of childbearing potential and males who have partners of childbearing potential must agree to use an effective contraceptive method during the study and for 30 days following the last dose of study drug
  • Females of childbearing potential must have a negative serum or urine beta-human chorionic gonadotropin (hCG) pregnancy test result within 7 days prior to the first dose of SGN-35
  • Females of non-childbearing potential are those who are postmenopausal greater than 1 year or who have had a bilateral tubal ligation or hysterectomy

Exclusion Criteria:

  • Unwilling or unable to comply with the protocol
  • Any other concurrent severe known disease (except carcinoma in-situ) or concurrent severe and/or uncontrolled medical condition (e.g. uncontrolled diabetes, or active uncontrolled infection) which could compromise participation in the study
  • History of another primary malignancy that has not been in remission for at least 3 years (the following are exempt from the 3-year limit: non-melanoma skin cancer, fully excised melanoma in situ [stage 0], curatively treated localized prostate cancer, and cervical carcinoma in situ on biopsy or a squamous intraepithelial lesion on Papanicolaou [PAP] smear)
  • Cardiovascular disease including congestive heart failure grade III or IV according to the New York Heart Association (NYHA) classification, left ventricular ejection fraction of < 50%, myocardial infarction within previous 6 months or poorly controlled hypertension
  • Pregnant or lactating
  • Neuropathy greater than or equal to grade 2
  • Known hypersensitivity to any excipient contained in the drug formulation
  • Confirmed diagnosis of human immunodeficiency virus (HIV) infection or active viral hepatitis
  • Presenting with an AHNMD requiring immediate cytoreductive therapy or targeted drugs (eg, AML)
  • Received any investigational agent, chemotherapy, interferon-alfa, or 2-chlorodeoxyadenosine (2-CdA, cladribine) within 30 days prior to Day 1
  • Received hematopoietic growth factor support within 14 days of Day 1 of SGN-35
  • Use of prednisone (or equivalent corticosteroid dose) for SM up to 10 mg/day or its equivalent is allowed, but it cannot have been started during screening; patients who are on prednisone up to 10 mg/day for medical problems unrelated to SM are also permitted on study
  • Presence of FIP1L1-PDGFR-alpha fusion even with resistance to imatinib
  • Received any treatment with SGN-35 prior to study entry
  • Any surgical procedure within 14 days of Day 1, excluding central venous catheter placement or other minor procedures (eg, skin biopsy)
  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: NCT01807598

Locations
United States, California
Stanford University Cancer Institute Recruiting
Stanford, California, United States, 94305
Contact: Isabel Reyes    650-725-4047    ilreyes@stanford.edu   
Principal Investigator: Jason R. Gotlib         
United States, Texas
MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Jennifer Longoria, RN    713-745-1216    jclongoria@mdanderson.org   
Sponsors and Collaborators
Jason Robert Gotlib
National Cancer Institute (NCI)
Investigators
Principal Investigator: Jason Gotlib Stanford University Hospitals and Clinics
  More Information

Responsible Party: Jason Robert Gotlib, Associate Professor of Medicine, Stanford University
ClinicalTrials.gov Identifier: NCT01807598     History of Changes
Other Study ID Numbers: HEMMPD0016  NCI-2013-00537  IRB-25727 
Study First Received: March 5, 2013
Last Updated: November 20, 2015
Health Authority: United States: Federal Government
United States: Food and Drug Administration
United States: Institutional Review Board
United States: Data and Safety Monitoring Board

Additional relevant MeSH terms:
Mastocytosis
Mastocytosis, Systemic
Leukemia, Mast-Cell
Skin Diseases
Leukemia
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Antibodies
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on December 05, 2016