Clinical trial NCT01807598: Brentuximab Vedotin in Treating Patients With Advanced Systemic Mastocytosis or Mast Cell Leukemia
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Aggressive Systemic Mastocytosis
Mast Cell Leukemia
Systemic Mastocytosis
Lead sponsor: Stanford University
Sponsor class: OTHER
Collaborators: name: Seagen Inc.
First posted: 2013-03-08
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

Detailed description: 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.

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 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)

Primary outcomes:
measure: Overall Response Rate (ORR) Per Consensus International Response Criteria (Rate of Complete or Partial Remissions or Clinical Improvement)
timeFrame: Up to 1 year
Secondary outcomes:
measure: Brentuximab Vedotin Toxicity
timeFrame: Up to 1 year
measure: Percent Change of CD30 Expression on Neoplastic Mast Cells
timeFrame: Baseline and up to 1 year
measure: Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) Total Symptom Score
timeFrame: Up to 1 year
measure: Quality of Life (QoL) Score Using a Modified Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF)
timeFrame: Up to 1 year
measure: Duration of Response (DOR)
timeFrame: Up to 1 year
measure: Time to Response (TTR)
timeFrame: Up to 1 year
measure: Progression-free Survival (PFS)
timeFrame: Up to 1 year
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford University, School of Medicine
state: California
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
Study officials:
affiliation: Stanford University Hospitals and Clinics
name: Jason Gotlib
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.