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

NCT01807598 | Completed Phase 2 Results DMC FDA Drug

• 4 other identifiers: IRB-25727NCI-2013-00537107011HEMMPD0016
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 2

Brief Summary

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

Conditions

Aggressive Systemic Mastocytosis; Mast Cell Leukemia; Systemic Mastocytosis

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (ORR) Per Consensus International Response Criteria (Rate of Complete or Partial Remissions or Clinical Improvement)

  Overall response rate (ORR) is sum of complete response (CR); partial response (PR); and clinical improvement (CI) in 1 year, ie, ORR=CR+PR+CI. The outcome is the number of participants without dispersion. CR is following with response duration(RD) ≥12 weeks (wk) * No mast cell disease * Tryptase \<20 ng/mL * Neutrophils ≥1x10e9/L with normal differential * Hemoglobin ≥11 g/dL * Platelets ≥100x10e9/L * No hepatosplenomegaly * No systemic mastocytosis(SM)-related organ damage PR is following with RD ≥12wk * Neither CR or progressive disease(PD) * Neoplastic mast cells reduced ≥50% * Tryptase reduced ≥50% * 1+ disease finding resolved CI is following with RD ≥12wk * Neither CR; PR; or PD * 1+ of findings above Stable disease (SD) Not CR, PR, Cl, or PD Progressive disease (PD) Any of: * Worsening organ damage * Doubling of laboratory abnormality * New transfusion dependence of ≥4 units red cells or platelets at 8wk •+ ≥100% in transfusions for 8wk * 10-cm+ splenomegaly

  Up to 1 year

Secondary Outcomes (7)

• Brentuximab Vedotin Toxicity

  Up to 1 year

• Percent Change of CD30 Expression on Neoplastic Mast Cells

  Baseline and up to 1 year

• Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) Total Symptom Score

  Up to 1 year

• Quality of Life (QoL) Score Using a Modified Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF)

  Up to 1 year

• Duration of Response (DOR)

  Up to 1 year

Study Arms (1)

Brentuximab vedotin

EXPERIMENTAL

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

Interventions

Brentuximab vedotin DRUG

Also known as: Adcetris, anti-CD30 antibody-drug conjugate, anti-CD30 ADC, SGN-35

Brentuximab vedotin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Jason Robert Gotlib: lead
• Seagen Inc.: collaborator

Study Sites (2)

Stanford University, School of Medicine

Stanford, California, 94305, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Gotlib J, Baird JH, George TI, Langford C, Reyes I, Abuel J, Perkins C, Schroeder K, Bose P, Verstovsek S. A phase 2 study of brentuximab vedotin in patients with CD30-positive advanced systemic mastocytosis. Blood Adv. 2019 Aug 13;3(15):2264-2271. doi: 10.1182/bloodadvances.2019000152.

  PMID: 31350306 DERIVED

MeSH Terms

Conditions

Mastocytosis, Systemic; Leukemia, Mast-Cell

Interventions

Brentuximab Vedotin

Condition Hierarchy (Ancestors)

Mastocytosis; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Mast Cell Activation Disorders; Immune System Diseases; Leukemia; Leukemia, Myeloid, Acute; Leukemia, Myeloid; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Jason R. Gotlib
• Organization: Stanford University

jason.gotlib@stanford.edu

650-736-1253

Study Officials

• Jason Gotlib

  Stanford University Hospitals and Clinics

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Medicine (Hematology)

Study Record Dates

• First Submitted: March 5, 2013
• First Posted: March 8, 2013
• Study Start: September 1, 2013
• Primary Completion: September 1, 2017
• Study Completion: September 1, 2017
• Last Updated: January 29, 2019
• Results First Posted: January 29, 2019

Record last verified: 2019-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)