Clinical Trials /

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

NCT01807598

Description:

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

Related Conditions:
  • Aggressive Systemic Mastocytosis
  • Mast Cell Leukemia
Recruiting Status:

Completed

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: 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)

Clinical Trial IDs

  • ORG STUDY ID: HEMMPD0016
  • SECONDARY ID: NCI-2013-00537
  • SECONDARY ID: IRB-25727
  • SECONDARY ID: 107011
  • NCT ID: NCT01807598

Conditions

  • Aggressive Systemic Mastocytosis
  • Mast Cell Leukemia
  • Systemic Mastocytosis

Interventions

DrugSynonymsArms
brentuximab vedotinAdcetris, anti-CD30 antibody-drug conjugate, anti-CD30 ADC, SGN-35Brentuximab vedotin

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

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.

Trial Arms

NameTypeDescriptionInterventions
Brentuximab vedotinExperimentalSubjects 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.
  • brentuximab vedotin

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)

Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall response rate per consensus international response criteria (rate of complete or partial remissions or clinical improvement)
Time Frame:Up to 1 year
Safety Issue:
Description:Will be estimated and its 95% confidence interval will be provided.

Secondary Outcome Measures

Measure:Immunohistochemical expression of CD30 on neoplastic mast cells in core biopsy samples by flow cytometry
Time Frame:Up to 1 year
Safety Issue:
Description:
Measure:Total symptom score using a modified Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF)
Time Frame:Up to 1 year
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:The Kaplan-Meier product-limit method will be used to summarize.
Measure:Time to response
Time Frame:Time from start of treatment until the date of onset of a confirmed response, assessed up to 1 year
Safety Issue:
Description:The Kaplan-Meier product-limit method will be used to summarize.
Measure: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
Safety Issue:
Description:The Kaplan-Meier product-limit method will be used to summarize.
Measure:Type of adverse events measured by National Cancer Institute Common Toxicity Criteria (NCI CTC) version 4.03
Time Frame:Up to 1 year
Safety Issue:
Description:
Measure:Quality of life (QOL) score using a modified Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF)
Time Frame:Up to 1 year
Safety Issue:
Description:
Measure:Incidence of adverse events measured by National Cancer Institute Common Toxicity Criteria (NCI CTC) version 4.03
Time Frame:Up to 1 year
Safety Issue:
Description:
Measure:Severity of adverse events measured by National Cancer Institute Common Toxicity Criteria (NCI CTC) version 4.03
Time Frame:Up to 1 year
Safety Issue:
Description:
Measure:Seriousness of adverse events measured by National Cancer Institute Common Toxicity Criteria (NCI CTC) version 4.03
Time Frame:Up to 1 year
Safety Issue:
Description:
Measure:Relatedness of adverse events measured by National Cancer Institute Common Toxicity Criteria (NCI CTC) version 4.03
Time Frame:Up to 1 year
Safety Issue:
Description:

Details

Phase:N/A
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Jason Robert Gotlib

Trial Keywords

    Last Updated

    December 13, 2016