Brentuximab Vedotin in Treating Patients With Advanced Systemic Mastocytosis or Mast Cell Leukemia - Full Text View

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 Other: laboratory biomarker analysis Procedure: quality-of-life assessment Other: questionnaire administration

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:

Genetics Home Reference related topics: familial acute myeloid leukemia with mutated CEBPA

MedlinePlus related topics: Cancer Leukemia

Drug Information available for: Brentuximab vedotin

U.S. FDA Resources

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:	26
Study Start Date:	June 2013
Estimated Primary Completion Date:	June 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Treatment (brentuximab vedotin) Patients receive brentuximab vedotin IV over 30 minutes on day 1. Treatment repeats every 21 days for 8 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 Procedure: quality-of-life assessment Ancillary studies Other Name: quality of life assessment Other: questionnaire administration Ancillary studies

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
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Patient must give 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
Patients with ASM and MCL with or without an AHNMD are required to have at least one of the eligible organ damage findings as defined by the international consensus response criteria
Both 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:

Patients 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)
Patients with 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
Women who are pregnant or lactating
Patients with >= grade 2 neuropathy
Patients with a known hypersensitivity to any excipient contained in the drug formulation
Confirmed diagnosis of human immunodeficiency virus (HIV) infection or active viral hepatitis
Patients presenting with an AHNMD requiring immediate cytoreductive therapy or targeted drugs (e.g. AML)
Patients who have received any investigational agent, chemotherapy, interferon-alfa, or 2-chlorodeoxyadenosine (2-CdA, cladribine) within 30 days prior to Day 1
Patients who have 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
Patients with the FIP1L1-PDGFRalpha fusion even with resistance to imatinib (such patients are no longer defined as systemic mastocytosis by the WHO)
Patients who have received any treatment with SGN-35 prior to study entry
Patients who have had any surgical procedure, excluding central venous catheter placement or other minor procedures (e.g. skin biopsy) within 14 days of Day 1

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01807598

Contacts

Contact: Harshdeep Kaur

650-723-3589

hkaur@stanford.edu

Locations

United States, California
Stanford University Cancer Institute	Not yet recruiting
Stanford, California, United States, 94305
Principal Investigator: Jason R. Gotlib

Sponsors and Collaborators

Stanford University

National Cancer Institute (NCI)

Investigators

Principal Investigator:

Jason Gotlib

Stanford University Hospitals and Clinics

More Information

No publications provided

Responsible Party:	Stanford University
ClinicalTrials.gov Identifier:	NCT01807598 History of Changes
Other Study ID Numbers:	HEMMPD0016, NCI-2013-00537
Study First Received:	March 5, 2013
Last Updated:	March 6, 2013
Health Authority:	United States: Federal Government

Additional relevant MeSH terms:

Mastocytosis
Urticaria Pigmentosa
Mastocytoma
Mastocytosis, Systemic
Mastocytosis, Cutaneous
Aggression
Leukemia
Leukemia, Mast-Cell
Behavioral Symptoms
Neoplasms by Histologic Type
Neoplasms

Leukemia, Myeloid, Acute
Leukemia, Myeloid
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Skin Diseases
Pigmentation Disorders
Antibodies, Monoclonal
Immunoconjugates
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on June 13, 2013