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
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
10
Stanford University, School of Medicine
Stanford, California, United States
MD Anderson Cancer Center
Houston, Texas, United States
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
Time frame: Up to 1 year
Brentuximab Vedotin Toxicity
Toxicity was assessed as the number of adverse events considered possibly, probably, or definitely-related to treatment with brentuximab vedotin. The outcome is reported as the total number of related events, a number without dispersion, and the number of related events (without dispersion) considered to be either a hematologic toxicity or non-hematologic toxicity.
Time frame: Up to 1 year
Percent Change of CD30 Expression on Neoplastic Mast Cells
The presence of the CD30 marker (epitope) on neoplastic (cancerous) mast cells in core bone marrow biopsy samples was assessed by immunohistochemical methods, before and after brentuximab vedotin treatment. CD30 is a member of the TNF-receptor (TNF-R) superfamily, and is a transmembrane glycoprotein receptor that is normally at very low levels on the surface of activated T-cells. Overexpression of the CD30 marker is indicative of T-cell lymphoproliferative disorders and neoplastic mast cells, and the effect of a particular treatment on CD30 expression may be related to the efficacy of that treatment. The outcome is reported as the median percentage change in the level of CD30 detected, reported with full range.
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Time frame: Baseline and up to 1 year
Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) Total Symptom Score
The clinical effect of patient symptoms associated with systemic mastocytosis or mast cell leukemia were assessed with the patient-reported outcome survey entitled Myeloproliferative Neoplasm Symptom Assessment Form with Mast Cell Disorder Symptoms \[(MPN-SAF(MCD)\]. The MPN-SAF(MCD) is a 36-question survey, with possible responses ranged from 0 to 10, with 0 indicating not present or no effect; 1 meaning present but most favorable; and 10 meaning worst imaginable (least favorable). Total range is 0 to 360, with 0 being best possible, and 360 being worst possible. Total symptom score is calculated as the sum of the individual survey scores reported at baseline and after treatment, with lower numbers indicating less effect, and larger numbers indicated greater effect. The outcome is reported as mean score value with dispersion.
Time frame: Up to 1 year
Quality of Life (QoL) Score Using a Modified Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF)
Overall quality of life (QoL) was assessed by a single specific question from the 36-question Myeloproliferative Neoplasm Symptom Assessment Form with Mast Cell Disorder Symptoms \[(MPN-SAF(MCD)\] survey. Possible responses for theQoL question range from 0 to 10, with 0 indicating "as good as it can be" (most favorable), and 10 meaning "as bad as it can be" (least favorable). The QoL score was obtained at baseline and after treatment. The outcome is reported as mean score with dispersion.
Time frame: Up to 1 year
Duration of Response (DOR)
Duration of response (DOR) is defined as the time from the start of the first confirmed response until the date of the first documented and confirmed disease progression or death due to ASM or MCL. For participants with a confirmed clinical response, the outcome was to be reported as the median DOR with standard deviation.
Time frame: Up to 1 year
Time to Response (TTR)
Time to response (TTR) is defined as the time from the date of start of treatment to the date of first confirmed response. For participants with a confirmed clinical response, the outcome was to be reported as the median TTR with standard deviation.
Time frame: Up to 1 year
Progression-free Survival (PFS)
Progression-free survival (PFS) is defined as the time from the date of start of treatment until disease progression; death; or initiation of new therapy. The outcome is reported as the mean number of days of PFS, with 95% confidence interval. Progressive disease (PD) is any of the following: * Worsening of any organ damage * Doubling of any laboratory abnormality * New transfusion dependence of ≥ 4 units red cells or platelets at 8 wk * ≥ 100% increase in transfusions for 8 wk * 10-cm+ splenomegaly
Time frame: Up to 1 year