Aggressive Systemic MastocytosisPhase 2NCT01807598
Brentuximab Vedotin in Treating Patients With Advanced Systemic Mastocytosis or Mast Cell Leukemia
A Phase 2 study testing Brentuximab vedotin in people with Aggressive Systemic Mastocytosis and Mast Cell Leukemia, run by Jason Robert Gotlib at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Aggressive Systemic Mastocytosis, Mast Cell Leukemia, Systemic Mastocytosis
- What is being tested?
- Brentuximab vedotin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 2 sitesUnited States
- Study dates
- Sep 2013to Sep 2017
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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)
Trial locations and contacts
2 sites in 1 country.
United States2 sites
MD Anderson Cancer Center
Houston, Texas, 77030
Stanford University, School of Medicine
Stanford, California, 94305
About this study
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)
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
Read the 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:
- 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:
- 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.
- Being tested
- Brentuximab vedotin
- Medical subject headings
- Mastocytosis, Systemic, Leukemia, Mast-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Brentuximab vedotinDrug
Also called Adcetris, anti-CD30 antibody-drug conjugate, anti-CD30 ADC, SGN-35
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Brentuximab vedotin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Up to 1 year
Secondary outcomes (7)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: Up to 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Mar 2013 (estimated)
- Study startSep 2013
- Primary completionSep 2017
- Study completionSep 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Aggressive Systemic MastocytosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Jason Robert Gotlib
- Sponsor type
- University, hospital or other
- Collaborators
- Seagen Inc.
- Responsible party
- Sponsor-investigator, Jason Robert Gotlib, Stanford University
- Investigators
- Jason Gotlib, Principal investigator, Stanford University Hospitals and Clinics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01807598
- Sponsor's protocol ID
- IRB-25727
- Other IDs
- NCI-2013-00537, IRB-25727, 107011, HEMMPD0016
- Status last verified
- Jan 2019
- First submitted
- 5 Mar 2013
- Last updated
- 29 Jan 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 31350306
Study at a glance
From the registry record, last updated by the sponsor on 29 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT01807598
- Acronym / sponsor ID
- IRB-25727
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Jason Robert GotlibUniversity, hospital or other
- Collaborators
- Seagen Inc.
- Study start
- Sep 2013
- Primary completion
- Sep 2017 (actual)
- Study completion
- Sep 2017 (actual)
- First posted
- 8 Mar 2013 (estimated)
- Results
- Posted 29 Jan 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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:
- 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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Brentuximab vedotin | Experimental | Drug: Brentuximab vedotinSubjects 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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
Key exclusion criteria (15 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Brentuximab vedotinAlso: Adcetris, anti-CD30 antibody-drug conjugate, anti-CD30 ADC, SGN-35 | Drug | Brentuximab vedotin |
Primary outcome
Overall Response Rate (ORR) Per Consensus International Response Criteria (Rate of Complete or Partial Remissions or Clinical Improvement)
Time frame: Up to 1 year
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
7 secondary outcomes
Brentuximab Vedotin Toxicity
Time frame: Up to 1 year
Percent Change of CD30 Expression on Neoplastic Mast Cells
Time frame: Baseline and up to 1 year
Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) Total Symptom Score
Time frame: Up to 1 year
Quality of Life (QoL) Score Using a Modified Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF)
Time frame: Up to 1 year
Duration of Response (DOR)
Time frame: Up to 1 year
Time to Response (TTR)
Time frame: Up to 1 year
Progression-free Survival (PFS)
Time frame: Up to 1 year
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jan 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 31350306Gotlib 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jason Gotlib principal investigator
Stanford University Hospitals and Clinics
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Brentuximab vedotin in people with Aggressive Systemic Mastocytosis and Mast Cell Leukemia, run by Jason Robert Gotlib at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Jan 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 29 Jan 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Response Rate (ORR) Per Consensus International Response Criteria (Rate of Complete or Partial Remissions or Clinical Improvement) (time frame: Up to 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01807598, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jan 2019.