- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02341014
Combination Therapy With Carfilzomib, Romidepsin, Lenalidomide in Patients With Relapsed or Refractory B- and T-cell Lymphomas
March 6, 2024 updated by: Memorial Sloan Kettering Cancer Center
Phase Ib/IIa Study of Combination Therapy With Carfilzomib, Romidepsin, Lenalidomide in Patients With Relapsed or Refractory B- and T-cell Lymphomas
This is an open label phase Ib/IIa study of patients with relapsed/refractory B- and T-cell lymphomas who are treated with carfilzomib, lenalidomide and romidepsin.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
27
Phase
- Phase 2
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
Nebraska
-
Omaha, Nebraska, United States, 68198-7680
- University of Nebraska Medical Center
-
-
New Jersey
-
Basking Ridge, New Jersey, United States, 07920
- Memoral Sloan Kettering Cancer Center
-
-
New York
-
Commack, New York, United States, 11725
- Memorial Sloan Kettering Cancer Center @ Suffolk
-
Harrison, New York, United States, 10604
- Memorial Sloan Kettering Westchester
-
New York, New York, United States, 10065
- Memorial Sloan Kettering Cancer Center
-
Rockville Centre, New York, United States, 11570
- Memorial Sloan Kettering at Mercy Medical Center
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
Inclusion Criteria:
- Pathologically confirmed B- or T-cell lymphomas at the enrolling institution, including stage ≥ Ib CTCL, which has relapsed or progressed after at least one systemic therapy.
- Hodgkin lymphoma is allowed and will be classified as a B-cell lymphoma in the phase IIA portion.
- Age ≥ 18,
- Previous systemic anti-cancer therapy must have been discontinued at least 3 weeks prior to treatment and adverse effects must have resolved to ≤Grade 1 or baseline. In the phase IIa portion, in progressing subjects, a 2 week washout may be allowed after discussion with the MSK Principal Investigator.
- Previous radiation, hormonal therapy, and/or surgery must have been discontinued or completed at least 2 weeks prior to treatment in this study and adverse effects must have resolved. Lymph node or other diagnostic biopsies within 2 weeks are not considered exclusionary.
- ECOG ≤ 2
- Meet the following laboratory criteria:
- Absolute neutrophil count 1.0/mm³,
- Platelet count 80 K/μ (in the Phase II portion, if thrombocytopenia is due to bone marrow involvement platelet count must be 50 K/μL),
- Phase Ib subjects must have calculated creatinine clearance 50ml/min by Cockcroft-Gault formula, phase IIa subjects must have calculated creatinine clearance ≥ 40ml4/min by Cockcroft-Gault formula.
- Total bilirubin 1.5 x upper limit of normal (ULN); AST (SGOT) and ALT (SGPT) 3 x ULN
- Measurable disease for phase IIa portion only.
- Lymphoma (includes CTCL patients who are without evidence of the disease in the skin): CT or PET/CT by modified Cheson criteria with incorporation of PET.
- CTCL: mSWAT >0, or absolute Sezary count ≥ 1000 cells/μL.
- All study participants must be registered into the mandatory Revlimid REMS ® program, and be willing and able to comply with the requirements of the REMS ® program.
- Short course systemic corticosteroids for disease control, improvement of performance status or non-cancer indication (< 7 days) must have been discontinued at least 6 days prior to study treatment. Stable ongoing corticosteroid use (≥ 30 days) up to an equivalent dose of 15 mg of prednisone is permissible.
- Topical steroids that have been used for > 3 weeks may be continued (CTCL only).
- Women of reproductive potential must adhere to the scheduled pregnancy testing as required in the Revlimid REMS® program. Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy. See Appendix A: Risks of Fetal Exposure, Pregnancy Testing Guidelines and Acceptable Birth Control Methods.
- A female of reproductive potential is a sexually mature female who:
- has not undergone a hysterectomy or bilateral oophorectomy; or has not been naturally postmenopausal for at least 24 consecutive months (i.e. has had menses at any time in the preceding 24 consecutive months).
Exclusion Criteria:
- Patients who have a standard curative option for their lymphoid malignancy at current state of disease are excluded. For eligibility on this trial, allogeneic stem cell transplantation is not to be considered a standard curative option.
- Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.
- Pregnant females. (Lactating females must agree not to breast feed while taking carfilzomib, lenalidomide or romidepsin).
- Known hypersensitivity to thalidomide.
- The development of erythema multiforme if characterized by a desquamating rash while taking thalidomide or similar drugs.
- Prior use of lenalidomide if discontinued due to toxicity.
- Prior therapy with romidepsin if discontinued due to toxicity.
- Prior therapy with carfilzomib if discontinued due to toxicity.
- Prior therapy with a proteasome inhibitor if discontinued due to toxicity.
- Concurrent use of other anti-cancer agents or treatments.
- Known seropositive and requiring anti-viral therapy for human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV).
- Concurrent malignancy requiring active therapy.
- Patients with more than one type of lymphoma may be enrolled after discussion with the MSK Principal Investigator.
- Known central nervous system or meningeal involvement (in the absence of symptoms investigation into central nervous system involvement is not required).
- The following known cardiac abnormalities:
- Congenital long QT syndrome.
- QTc/QTf interval ≥ 480 milliseconds; unless secondary to pacemaker or bundle branch block.
- Myocardial infarction within 6 months of cycle one, day one (C1D1). Subjects with a history of myocardial infarction between 6 and 12 months prior to C1D1 who are asymptomatic and have had a negative cardiac risk assessment (treadmill stress test, nuclear medicine stress test, or stress echocardiogram) since the event may participate.
- Other significant ECG abnormalities including 2nd degree atrio-ventricular (AV) block type II, 3rd degree AV block.
- Symptomatic coronary artery disease (CAD), e.g., angina Canadian Class II-IV (see Appendix B). In any patient in whom there is doubt, the patient should have a stress imaging study and, if abnormal, angiography to define whether or not CAD is present.
- An ECG recorded at screening showing evidence of cardiac ischemia (ST depression of ≥2 mm, measured from isoelectric line to the ST segment). If in any doubt, the patient should have a stress imaging study and, if abnormal, angiography to define whether or not CAD is present.
- Congestive heart failure (CHF) that meets New York Heart Association (NYHA) Class II to IV definitions (see Appendix C) and/or ejection fraction <45% by, echocardiogram, or cardiac MRI.
- A known history of sustained ventricular tachycardia (VT), ventricular fibrillation (VF), Torsade de Pointes, or cardiac arrest unless currently addressed with an automatic implantable cardioverter defibrillator (AICD).
- Hypertrophic cardiomegaly or restrictive cardiomyopathy from prior treatment or other causes.
- Uncontrolled hypertension, i.e., blood pressure (BP) of ≥170/95; patients who have a history of hypertension controlled by medication must be on a stable dose (for at least one month) and meet all other inclusion criteria.
- Any cardiac arrhythmia requiring an anti-arrhythmic medication (excluding stable doses of beta-blockers)
- Patients taking drugs that can cause significant QTc/QTf prolongation unless able to be switched to non-QTc/QTf prolonging medication or on a stable dose without significant QT prolongation (>470 msec).
- Concomitant use of significant CYP3A4 inhibitors unless able to be switched to a non-CYP3A4 inhibiting medication.
- Caution should be used when administering study drugs to patients taking medications significantly metabolized by these enzymes refer to (http://medicine.iupui.edu/clinpharm/ddis/clinical-table/ ) for clinically relevant medications. Particular attention should be paid to patients receiving warfarin. Patient should have coagulation parameters monitored regularly, and warfarin dose adjusted accordingly. If these drugs cannot be discontinued or replaced, enrollment may be allowed after discussion with MSK PI.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Carfilzomib, Romidepsin, Lenalidomide
All patients will be treated with romidepsin administered intravenously on days 1 and 8 of a 21-day cycle.
Lenalidomide will be taken orally daily for days 1-14 of a 21-day cycle.
The carfilzomib will be given weekly on days 1, and 8 of a 21-day cycle.
|
The initial dose of carfilzomib (cycle 1, day 1) given to any patient must be 20mg/m2 .
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Maximum Tolerated Dose of Romidepsin
Time Frame: 21 days
|
Determine the MTD by NCI-CTCAE v4.0.
|
21 days
|
Maximum Tolerated Dose of Lenalidomide
Time Frame: 21 days
|
Determine the MTD by NCI-CTCAE v4.0.
|
21 days
|
Maximum Tolerated Dose of Carfilzomib
Time Frame: 21 days
|
Determine the MTD by NCI-CTCAE v4.0.
|
21 days
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall Response Rate (Orr) at the Maximum Tolerated Dose
Time Frame: 1 year
|
will be summarized using percentages and confidence intervals will be provided.
ORR will be calculated based on the best response at any time during the course of treatment on this protocol.
|
1 year
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Collaborators
Investigators
- Principal Investigator: Steven Horwitz, MD, Memorial Sloan Kettering Cancer Center
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Helpful Links
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
January 2, 2015
Primary Completion (Actual)
January 11, 2023
Study Completion (Actual)
January 11, 2023
Study Registration Dates
First Submitted
January 14, 2015
First Submitted That Met QC Criteria
January 14, 2015
First Posted (Estimated)
January 19, 2015
Study Record Updates
Last Update Posted (Actual)
April 4, 2024
Last Update Submitted That Met QC Criteria
March 6, 2024
Last Verified
January 1, 2023
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Lymphoma, Non-Hodgkin
- Lymphoma
- Lymphoma, T-Cell
- Lymphoma, T-Cell, Peripheral
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Immunologic Factors
- Angiogenesis Inhibitors
- Angiogenesis Modulating Agents
- Growth Substances
- Growth Inhibitors
- Antibiotics, Antineoplastic
- Histone Deacetylase Inhibitors
- Lenalidomide
- Romidepsin
Other Study ID Numbers
- 14-179
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on T-cell Lymphomas
-
Stanford UniversityNational Institutes of Health (NIH); AmgenCompletedLymphoma, Non-Hodgkin | Lymphomas: Non-Hodgkin | Lymphomas: Non-Hodgkin Peripheral T-Cell | Lymphomas: Non-Hodgkin Cutaneous Lymphoma | Lymphomas: Non-Hodgkin Diffuse Large B-Cell | Lymphomas: Non-Hodgkin Follicular / Indolent B-Cell | Lymphomas: Non-Hodgkin Mantle Cell | Lymphomas: Non-Hodgkin Marginal... and other conditionsUnited States
-
Memorial Sloan Kettering Cancer CenterActive, not recruitingT-cell Large Granular Lymphocyte Leukemia | T-cell Lymphomas | T-cell Prolymphocytic Leukemia | NK-Cell LymphomasUnited States
-
Stanford UniversityTerminatedMycosis Fungoides | Lymphomas: Non-Hodgkin | Lymphomas: Non-Hodgkin Peripheral T-Cell | Lymphomas: Non-Hodgkin Cutaneous LymphomaUnited States
-
Assistance Publique - Hôpitaux de ParisActive, not recruitingEpidermotropic T-cell LymphomasFrance
-
National Health Research Institutes, TaiwanNational Taiwan University Hospital; China Medical University Hospital; Chang... and other collaboratorsNot yet recruitingPeripheral T-cell Lymphomas (PTCL)Taiwan
-
Memorial Sloan Kettering Cancer CenterDana-Farber Cancer Institute; Stanford UniversityActive, not recruitingLymphoma | Relapsed/Refractory T-cell LymphomasUnited States
-
Fudan UniversityUnknownChemotherapy | T-Cell LymphomasChina
-
Ontario Clinical Oncology Group (OCOG)Sunnybrook Health Sciences Centre; Genzyme, a Sanofi CompanyCompletedAlemtuzumab and CHOP Chemotherapy for Aggressive Histological Peripheral T-Cell Lymphomas (ACCAPELA)Peripheral T-cell LymphomasCanada
-
Nanjing NingQi Medicine Science and Technology...Jiangsu Cancer Institute & HospitalUnknownPeripheral T-cell LymphomasChina
-
Bristol-Myers SquibbRecruitingRelapsed or Refractory T-cell LymphomasJapan
Clinical Trials on Lenalidomide
-
Sidney Kimmel Comprehensive Cancer Center at Johns...TerminatedMyelodysplastic SyndromeUnited States
-
Grupo Español de Linfomas y Transplante Autólogo...Celgene Corporation; Dynamic Science S.L.; Thermo Fisher Scientific, IncCompleted
-
Celgene CorporationICON Clinical ResearchCompletedMyelodysplastic SyndromesGermany, Israel, United Kingdom, Spain, Belgium, Italy, France, Netherlands, Sweden
-
Boston VA Research Institute, Inc.Celgene Corporation; Edward Hines Jr. VA Hospital; Michael E. DeBakey VA Medical... and other collaboratorsCompletedMultiple MyelomaUnited States
-
Swiss Group for Clinical Cancer ResearchTerminatedLymphomaSwitzerland, Norway, Sweden
-
Dana-Farber Cancer InstituteBeth Israel Deaconess Medical Center; Genentech, Inc.; Brigham and Women's Hospital and other collaboratorsTerminatedWaldenstrom's MacroglobulinemiaUnited States
-
University Hospital, ToulouseCelgene Corporation; Janssen-Cilag Ltd.Completed
-
CelgeneCompletedRelapsed or Refractory Chronic Lymphocytic LeukemiaUnited States, Canada, United Kingdom, France, Germany, Spain, Italy, Sweden
-
Groupe Francophone des MyelodysplasiesUnknownMyelodysplastic SyndromesFrance