CD30-Positive Neoplastic Cells PresentPhase 1NCT03373305
Brentuximab Vedotin and Lenalidomide in Treating Patients With Relapsed or Refractory T-Cell Lymphomas
A Phase 1 study testing Brentuximab Vedotin, Lenalidomide and Laboratory Biomarker Analysis in people with CD30-Positive Neoplastic Cells Present and Folliculotropic Mycosis Fungoides, run by City of Hope Medical Center at 1 site in United States.
Trial summary
This phase I trial studies the side effects and best dose of lenalidomide when given together with brentuximab vedotin in treating patients with T-cell lymphomas that have come back or do not respond to treatment. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- CD30-Positive Neoplastic Cells Present, Folliculotropic Mycosis Fungoides, Recurrent Mycosis Fungoides
- What is being tested?
- Brentuximab Vedotin, Lenalidomide and Laboratory Biomarker Analysis
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2019to 26 Apr 2019
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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
- Documented informed consent of the participant and/or legally authorized representative
- Registered into mandatory Revlimid Risk Evaluation and Mitigation Strategies (REMS) program
- Women of childbearing potential: adhere to scheduled pregnancy testing as required in the Revlimid REMS program
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
- Histologically confirmed cutaneous T-cell non-Hodgkin lymphoma (CTCL) per World Health Organization (WHO) classification 2016 including, mycosis fungoides (MF) or Sezary syndrome (SS); phase 1 : >= stage IIB OR >= stage IB-IIA folliculotropic/transformed MF; expansion cohort: >= stage IB
- MF/SS stage of disease according to TNMB classification
Show all 26Show fewer
- SS is defined as meeting T4 plus B2 criteria; where the biopsy of erythrodermic skin may only reveal suggestive but not diagnostic histopathologic features, the diagnosis may be based on either node biopsy or fulfillment of B2 criteria
- For MF where the histological diagnosis by light microscopic examination is not confirmed, diagnostic criteria that been recommended by the International Society for Cutaneous Lymphomas (ISCL) should be used
- Relapsed/refractory disease
- Failed >= 2 prior systemic therapies
- CD30-positivity by immunohistochemistry of >= 1%
- Measurable disease per modified Severity Weighted Assessment and/or Sezary count
- Fully recovered from acute toxicities (except alopecia) of all prior therapies to Common Terminology Criteria for Adverse Events (CTCAE) =< grade 1
- May have received either brentuximab vedotin or lenalidomide/immunomodulatory imide drugs (IMiD) without dose modification/delay due to toxicity
- IMiDs defined as thalidomide analogues
- If received prior brentuximab vedotin or lenalidomide, must be able to tolerate the dose level to which the participant will be enrolled to
- Within 14 days prior to day 1 of protocol therapy unless otherwise stated: Absolute neutrophil count (ANC) >= 1,000/mm^3
- NOTE: Growth factor is not permitted within 14 days of ANC assessment unless cytopenia is secondary to disease involvement
- Within 14 days prior to day 1 of protocol therapy unless otherwise stated: Platelets >= 75,000/mm^3
- NOTE: Platelet transfusions are not permitted within 14 days of platelet assessment unless cytopenia is secondary to disease involvement
- Within 14 days prior to day 1 of protocol therapy unless otherwise stated: Total bilirubin =< 1.5 X upper limit of normal (ULN) OR if Gilbert's syndrome =< 3.0 X ULN
- Within 14 days prior to day 1 of protocol therapy unless otherwise stated: Aspartate aminotransferase (AST) =< 2 x ULN
- Within 14 days prior to day 1 of protocol therapy unless otherwise stated: Alanine aminotransferase (ALT) =< 2 x ULN
- Within 14 days prior to day 1 of protocol therapy unless otherwise stated: Creatinine clearance of >= 60 mL/min per 24 hour urine test or the Cockcroft-Gault formula
- Within 14 days prior to day 1 of protocol therapy unless otherwise stated: Women of childbearing potential (WOCBP): negative urine or serum pregnancy test; if the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
- Agreement by WOCBP and males of childbearing potential to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least 6 months after the last dose of protocol therapy * Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for > 1 year (women only)
Who cannot join
- Stem cell transplantation
- Monoclonal antibody within 28 days prior to day 1 of protocol therapy
- Any systemic therapy, including monoclonal antibody within 28 days or 5 half-lives (whichever is shorter) of initiating day 1 of protocol therapy
- Any skin-directed therapy within 14 days prior to day 1 of protocol therapy
- Any radiation therapy within 21 days prior to day 1 of protocol therapy
- Immunosuppressive medication within 14 days prior to day 1 of protocol therapy; the following are exceptions to this criterion:
Show all 32Show fewer
- Intranasal, inhaled, topical or local steroid injections (e.g., intra-articular injection) and are on stable dose for at least 28 days
- Systemic corticosteroids at physiologic doses of < 10 mg/day of prednisone or equivalent
- Live, attenuated vaccine within 30 days prior to day 1 of protocol therapy
- Disease free of prior malignancies for >= 5 years with the exception of:
- Currently treated squamous cell and basal cell carcinoma of the skin, or
- Carcinoma in situ of the cervix, or
- Surgically removed melanoma in situ of the skin (stage 0) with histological confirmed free margins of excision , or
- Prostate cancer (T1a or T1b using the TNM [tumor, nodes, metastasis] clinical staging system) that has/have been surgically cured, or
- Any other malignancy that has/have been curatively treated with surgery and/or localized radiation
- Allergic reaction/hypersensitivity to lenalidomide or history of anaphylactic shock to brentuximab vedotin in the past
- Female only: pregnant or breastfeeding
- Acute infection requiring systemic treatment
- Known history of human immunodeficiency virus (HIV) infection
- Active hepatitis B or C infection
- Central nervous system involvement by lymphoma, including leptomeningeal involvement
- History of progressive multifocal leukoencephalopathy (PML)
- Current peripheral neuropathy >= grade 2 or patients with the demyelinating form of Charcot-Marie-Tooth syndrome
- Unstable cardiac disease as defined by one of the following:
- Cardiac events such as myocardial infarction (MI) within the past 6 months
- NYHA (New York Heart Association) heart failure class III-IV
- Uncontrolled atrial fibrillation or hypertension
- History of vascular disease (e.g. deep vein thrombosis, stroke)
- Major surgery (as defined by the investigator) within the 28 days prior to day 1 of protocol therapy
- Incidence of gastrointestinal disease that may significantly alter the absorption of lenalidomide
- Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns or compliance with clinical study procedures, e.g., infection/inflammation, intestinal obstruction, unable to swallow medication, social/psychological issues, etc.
- Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)
Trial locations and contacts
1 site in 1 country.
United States1 site
City of Hope Medical Center
Duarte, California, 91010
About this study
Official title: A Phase 1 Trial of Brentuximab Vedotin Plus Lenalidomide in Patients With Relapsed/ Refractory Cutaneous T-Cell Lymphomas
This phase I trial studies the side effects and best dose of lenalidomide when given together with brentuximab vedotin in treating patients with T-cell lymphomas that have come back or do not respond to treatment. Monoclonal antibodies, such as brentuximab vedotin, may interfere with the ability of cancer cells to grow and spread. Drugs used in chemotherapy, such as lenalidomide, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving brentuximab vedotin and lenalidomide may work better in treating patients with T-cell lymphomas.
Read the detailed description
PRIMARY OBJECTIVES:
- Determine the maximum tolerated dose (MTD)/Recommended Phase 2 dose (RP2D) of brentuximab vedotin in combination with lenalidomide in patients with relapsed/ refractory cutaneous T-cell lymphoma (CTCL).
II. Assess safety and tolerability of brentuximab vedotin in combination with lenalidomide in patients with relapsed/ refractory CTCL.
SECONDARY OBJECTIVES:
- Estimate the rate of objective global response that lasts at least 4 months (ORR4) , complete response (CR) rate, progression-free survival (PFS) of brentuximab vedotin in combination with lenalidomide in patients with relapsed/ refractory CTCL.
II. Estimate the rate and duration of clinically meaningful reduction in pruritus (CMRP).
III. Correlate response to baseline CD30 levels in tissue samples.
TERTIARY OBJECTIVES:
- Estimate the response endpoints incorporating Lugano response criteria for patients with PET+ disease.
II. Explore temporal gene expression profile in skin/ blood samples that may predict response to combination therapy.
OUTLINE: This is a dose-escalation study of lenalidomide.
Patients receive brentuximab vedotin intravenously (IV) over 30 minutes on day 1 and lenalidomide orally (PO) once daily (QD) on days 1-14. Treatment repeats every 21 days for up to 17 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days and then up to 12 months.
- Conditions
- CD30-Positive Neoplastic Cells Present, Folliculotropic Mycosis Fungoides, Recurrent Mycosis Fungoides, Recurrent Primary Cutaneous T-Cell Non-Hodgkin Lymphoma, Refractory Mycosis Fungoides, Refractory Primary Cutaneous T-Cell Non-Hodgkin Lymphoma
- Being tested
- Brentuximab Vedotin, Lenalidomide, Laboratory Biomarker Analysis
- Medical subject headings
- Mycosis Fungoides, Lymphoma, T-Cell, Cutaneous, Sezary Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Brentuximab VedotinDrug
Also called 914088-09-8, ADC SGN-35, Adcetris, Anti-CD30 Antibody-Drug Conjugate SGN-35
Given IV
LenalidomideDrug
Also called 191732-72-6, 3-(4-Amino-1-oxo-1,3-dihydro-2H-isoindol-2-yl)piperidine-2,6-dione, 703813, CC-5013
Given PO
Laboratory Biomarker AnalysisOther
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Treatment (brentuximab vedotin, lenalidomide) | Experimental | Patients receive brentuximab vedotin IV over 30 minutes on day 1 and lenalidomide PO QD on days 1-14. Treatment repeats every 21 days for up to 17 courses in the absence of disease progression or unacceptable toxicity. Receives: Drug: Brentuximab Vedotin; Drug: Lenalidomide; Other: Laboratory Biomarker Analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose limiting toxicity (DLT) assessed per CTCAE v4.0
Measured: Up to 21 days
Secondary outcomes (5)
Rate of objective global response defined as proportion of patients achieving complete response (CR)/partial response (PR) that lasts at least 4 months
Will be estimated by the proportion of patients achieving a CR/PR that lasts at least 4 months, along with the 95% exact binomial confidence interval.
Measured: At 4 months
Complete response defined as proportion of patients achieving CR according to Olsen criteria
Complete response rate will be estimated by the proportion of evaluable patients achieving CR, along with the 95% exact binomial confidence interval.
Measured: Up to 1 year
Progression free survival (PFS) according to Olsen criteria
PFS will be estimated using the product-limit method of Kaplan and Meier along with the Greenwood estimator of standard error.
Measured: From start of protocol treatment to first observation of disease relapse/ progression or death from any cause, whichever occurs first, assessed up to 1 year
Change in pruritus visual analogue scale (VAS)
Pruritus visual analogue scale (VAS) is a horizontal 100mm long line on which the patients make a vertical mark to indicate their subjective assessment of pruritus intensity; the patients are informed that the scale represents no pruritus (0 points) to severe pruritus (100 points). Changes from baseline over time in pruritus VAS score will be assessed using descriptive statistics.
Measured: Up to 1 year
CD30 expression assessed by lymph node and/or skin biopsies via immunochemistry
Baseline CD30 levels in tissue samples by immunochemistry will be compared between responders and non-responders by Fisher's exact test. Log rank test will be used to explore the association between baseline CD30 levels in tissue samples with PFS.
Measured: Baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Dec 2017
- Study startMar 2019 (estimated)
- Primary completion26 Apr 2019
- Study completion26 Apr 2019
Why it stopped: contract not executed
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for CD30-Positive Neoplastic Cells PresentStudies of the same condition, open and under way.
- More trials run by City of Hope Medical CenterThe sponsor's other registered studies.
- 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- City of Hope Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jasmine Zain, MD, Principal investigator, City of Hope Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03373305
- Sponsor's protocol ID
- 17347
- Other IDs
- NCI-2017-02163
- Status last verified
- Apr 2019
- First submitted
- 28 Nov 2017
- Last updated
- 30 Apr 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Trial of Brentuximab Vedotin Plus Lenalidomide in Patients With Relapsed/ Refractory Cutaneous T-Cell Lymphomas
- ClinicalTrials.gov ID
- NCT03373305
- Acronym / sponsor ID
- 17347
- Conditions
- CD30-Positive Neoplastic Cells Present, Folliculotropic Mycosis Fungoides, Recurrent Mycosis Fungoides, Recurrent Primary Cutaneous T-Cell Non-Hodgkin Lymphoma, Refractory Mycosis Fungoides, Refractory Primary Cutaneous T-Cell Non-Hodgkin Lymphoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: contract not executed
- Enrolment
- 0 participants (actual)
- Lead sponsor
- City of Hope Medical CenterUniversity, hospital or other
- Study start
- Mar 2019 (estimated)
- Primary completion
- 26 Apr 2019 (actual)
- Study completion
- 26 Apr 2019 (actual)
- First posted
- 14 Dec 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase I trial studies the side effects and best dose of lenalidomide when given together with brentuximab vedotin in treating patients with T-cell lymphomas that have come back or do not respond to treatment. Monoclonal antibodies, such as brentuximab vedotin, may interfere with the ability of cancer cells to grow and spread. Drugs used in chemotherapy, such as lenalidomide, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving brentuximab vedotin and lenalidomide may work better in treating patients with T-cell lymphomas.
Detailed description
PRIMARY OBJECTIVES:
- Determine the maximum tolerated dose (MTD)/Recommended Phase 2 dose (RP2D) of brentuximab vedotin in combination with lenalidomide in patients with relapsed/ refractory cutaneous T-cell lymphoma (CTCL).
II. Assess safety and tolerability of brentuximab vedotin in combination with lenalidomide in patients with relapsed/ refractory CTCL.
SECONDARY OBJECTIVES:
- Estimate the rate of objective global response that lasts at least 4 months (ORR4) , complete response (CR) rate, progression-free survival (PFS) of brentuximab vedotin in combination with lenalidomide in patients with relapsed/ refractory CTCL.
II. Estimate the rate and duration of clinically meaningful reduction in pruritus (CMRP).
III. Correlate response to baseline CD30 levels in tissue samples.
TERTIARY OBJECTIVES:
- Estimate the response endpoints incorporating Lugano response criteria for patients with PET+ disease.
II. Explore temporal gene expression profile in skin/ blood samples that may predict response to combination therapy.
OUTLINE: This is a dose-escalation study of lenalidomide.
Patients receive brentuximab vedotin intravenously (IV) over 30 minutes on day 1 and lenalidomide orally (PO) once daily (QD) on days 1-14. Treatment repeats every 21 days for up to 17 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days and then up to 12 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (brentuximab vedotin, lenalidomide) | Experimental | Drug: Brentuximab Vedotin, Drug: Lenalidomide, Other: Laboratory Biomarker AnalysisPatients receive brentuximab vedotin IV over 30 minutes on day 1 and lenalidomide PO QD on days 1-14. Treatment repeats every 21 days for up to 17 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 (26 listed)
- Documented informed consent of the participant and/or legally authorized representative
- Registered into mandatory Revlimid Risk Evaluation and Mitigation Strategies (REMS) program
- Women of childbearing potential: adhere to scheduled pregnancy testing as required in the Revlimid REMS program
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
- Histologically confirmed cutaneous T-cell non-Hodgkin lymphoma (CTCL) per World Health Organization (WHO) classification 2016 including, mycosis fungoides (MF) or Sezary syndrome (SS); phase 1 : >= stage IIB OR >= stage IB-IIA folliculotropic/transformed MF; expansion cohort: >= stage IB
Key exclusion criteria (32 listed)
- Stem cell transplantation
- Monoclonal antibody within 28 days prior to day 1 of protocol therapy
- Any systemic therapy, including monoclonal antibody within 28 days or 5 half-lives (whichever is shorter) of initiating day 1 of protocol therapy
- Any skin-directed therapy within 14 days prior to day 1 of protocol therapy
- Any radiation therapy within 21 days prior to day 1 of protocol therapy
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: 914088-09-8, ADC SGN-35, Adcetris, Anti-CD30 Antibody-Drug Conjugate SGN-35Given IV | Drug | Treatment (brentuximab vedotin, lenalidomide) |
| LenalidomideAlso: 191732-72-6, 3-(4-Amino-1-oxo-1,3-dihydro-2H-isoindol-2-yl)piperidine-2,6-dione, 703813, CC-5013Given PO | Drug | Treatment (brentuximab vedotin, lenalidomide) |
| Laboratory Biomarker AnalysisCorrelative studies | Other | Treatment (brentuximab vedotin, lenalidomide) |
Primary outcome
Dose limiting toxicity (DLT) assessed per CTCAE v4.0
Time frame: Up to 21 days
5 secondary outcomes
Rate of objective global response defined as proportion of patients achieving complete response (CR)/partial response (PR) that lasts at least 4 months
Time frame: At 4 months
Complete response defined as proportion of patients achieving CR according to Olsen criteria
Time frame: Up to 1 year
Progression free survival (PFS) according to Olsen criteria
Time frame: From start of protocol treatment to first observation of disease relapse/ progression or death from any cause, whichever occurs first, assessed up to 1 year
Change in pruritus visual analogue scale (VAS)
Time frame: Up to 1 year
CD30 expression assessed by lymph node and/or skin biopsies via immunochemistry
Time frame: Baseline
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Apr 2019.
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Active, not recruitingPhase 2
Brentuximab Vedotin in Treating Patients With CD30+ Malignant Mesothelioma That Cannot Be Removed by Surgery
CD30-Positive Neoplastic Cells Present, Malignant Mesothelioma
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.
Jasmine Zain, MD principal investigator
City of Hope Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Brentuximab Vedotin, Lenalidomide and Laboratory Biomarker Analysis in people with CD30-Positive Neoplastic Cells Present and Folliculotropic Mycosis Fungoides, run by City of Hope Medical Center at 1 site 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 26 inclusion and 32 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: withdrawn, as of the sponsor's last update on 30 Apr 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
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?
Dose limiting toxicity (DLT) assessed per CTCAE v4.0 (time frame: Up to 21 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 30 Apr 2019.