Multiple MyelomaPhase 1/2NCT01755975
Romidepsin in Combination With Lenalidomide in Adults With Relapsed or Refractory Lymphomas and Myeloma
A Phase 1/2 study testing Romidepsin and Lenalidomide in people with Multiple Myeloma and Non-Hodgkin's Lymphoma, run by Memorial Sloan Kettering Cancer Center at 7 sites in United States.
Trial summary
The treatments used to treat lymphoma and multiple myeloma sometimes do not always work well or they may only work for a short period of time. This is why new treatments are being tested. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Multiple Myeloma, Non-Hodgkin's Lymphoma
- What is being tested?
- Romidepsin and Lenalidomide
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 49 participants
- Where
- 7 sitesUnited States
- Study dates
- Dec 2012to Oct 2023
- Phase
- Phase 1/2
- 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
- Pathology confirmed lymphoma or multiple myeloma
- Hodgkin lymphoma is eligible for either phase and will be considered a B-cell lymphoma in the phase IIa study.
- Phase IIa portion, subjects must have B-cell lymphoma, T-cell lymphoma, or multiple myeloma.
- Relapse or progression after at least 1 systemic therapy.
- Measurable disease for phase IIa portion only.
- Lymphoma (includes CTCL patients who are NED in skin): CT or PET/CT by modified Cheson criteria with incorporation of PET.
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- Multiple myeloma:.Patient must have measurable disease and therefore must have at least one of the following:
- Serum M-protein ≥0.5gm/dL (≥5gm/L) ii. Urine M-protein ≥200mg/24hr iii. Serum FLC assay: involved FLC ≥10mg/dL (≥100mg/L) provided serum FLC ratio is abnormal.
- CTCL: mSWAT >0, or absolute Sezary count ≥ 1000 cells/μL.
- Age ≥18 years at the time of signing the informed consent form.
- Able to adhere to the study visit schedule and other protocol requirements.
- Previous systemic anti-cancer therapy must have been discontinued at least 3 weeks prior to treatment in this study. If there is progression of disease on that therapy and all adverse effects have resolved to Grade 1 or baseline, in which case 2 weeks is acceptable.
- Previous radiation, hormonal therapy, and 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 biopsy within 2 weeks is not considered exclusionary.
- Short course systemic corticosteroids for disease control, improvement of performance status or non-cancer indication (< 7 days) must have been discontinued at least 7 days prior to study treatment. Stable ongoing corticosteroid use (≥ 30 days) up to an equivalent dose of 15 mg of prednisone is permissible.
- ECOG performance status of ≤ 2 at study entry
- Laboratory test results within these ranges:
- Absolute neutrophil count ≥ 1.0/mm³.
- Platelet count ≥ 70 K/μL, if thrombocytopenia is due to bone marrow involvement platelet count must be ≥ 50 K/μL.
- Renal function assessed by calculated creatinine clearance as follows
- Phase Ib subjects must have calculated creatinine clearance ≥ 50ml/min by Cockcroft-Gault formula.
- Phase IIa subjects must have calculated creatinine clearance ≥ 30ml/min by Cockcroft-Gault formula. See section below, "Dosing Regimen", regarding lenalidomide dose adjustment for calculated creatinine clearance < 60ml/min and ≥ 30ml/min.
- Total bilirubin ≤ 1.5 x upper limit of normal (ULN); 3 x ULN if due to hepatic involvement.
- AST (SGOT) and ALT (SGPT) ≤ 3 x ULN; 5 x ULN if due to hepatic involvement.
- 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.
- Females 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 C: Risks of Fetal Exposure, Pregnancy Testing Guidelines and Acceptable Birth Control Methods. † A female of childbearing potential is a sexually mature female who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) 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).
Who cannot join
- 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 lenalidomide or romidepsin).
- Known hypersensitivity to thalidomide.
- The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs.
- Prior use of lenalidomide if discontinued due to toxicity.
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- Prior therapy with romidepsin 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).
- Active concurrent malignancy requiring active therapy.
- Known central nervous system or meningeal involvement (in the absence of symptoms investigation into central nervous system involvement is not required). Patients with HTLV1 ATLL and controlled CNS or meningeal involvement may be enrolled after discussion with the MSK principal investigator.
- The following known cardiac abnormalities:
- Congenital long QT syndrome.
- QTc interval ≥ 480 milliseconds
- A QTc interval between 480-499 msec in the presence of a bundle branch block (BBB) or pacemaker is are eligible in phase IIa after discussion with the MSK principal investigator
- 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 D). 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 E) and/or ejection fraction <45% by MUGA, 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 leading to significant QTc prolongation unless able to be switched to non-QTc prolonging medication without risk of worsening underlying condition and meet all other inclusion criteria: Medications That May Cause QTc Prolongation).
- Concomitant use of significant CYP3A4 inhibitors unless able to be switched to a non-CYP3A4 inhibiting medication without risk of worsening underlying condition and able to meet all other inclusion criteria.
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
United States7 sites
Memorial Sloan Kettering at Basking Ridge
Basking Ridge, New Jersey, 07920
Memorial Sloan Kettering Cancer Center at Commack
Commack, New York, 11725
Saint Francis/Mount Sinai Regional Cancer Center
Hartford, Connecticut, 06105
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Weill Cornell Medical Center
New York, New York
University of Nebraska Medical Center
Omaha, Nebraska, 68198-7680
Memorial Sloan Kettering Cancer Center at Mercy
Rockville Centre, New York, 11570
About this study
Official title: A Phase Ib/IIa Study of Romidepsin in Combination With Lenalidomide in Adults With Relapsed or Refractory Lymphomas and Myeloma
The treatments used to treat lymphoma and multiple myeloma sometimes do not always work well or they may only work for a short period of time. This is why new treatments are being tested.
This study will test a new combination of two drugs that are already approved by the Food and Drug Administration for treatment of certain kinds of blood cancers. These drugs are romidepsin and lenalidomide. Both these drugs by themselves have been used to treat lymphoma or multiple myeloma. However, while these drugs are routinely used alone, this is the first time they will be tested together. The mechanism of action of both drugs is not well understood but both have been shown to to be effective by themselves in lymphoma and multiple myeloma.
- Conditions
- Multiple Myeloma, Non-Hodgkin's Lymphoma
- Being tested
- Romidepsin, Lenalidomide
- Keywords
- LENALIDOMIDE (CC-5013), Romidepsin (Istodax), 12-170
- Medical subject headings
- Multiple Myeloma, Lymphoma, Non-Hodgkin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RomidepsinDrug
Romidepsin will be administered intravenously on days 1, 8, and 15 of a 28-day cycle.
LenalidomideDrug
Lenalidomide will be taken orally daily for 21 days of a 28-day cycle.
| Study group | Role | What they receive |
|---|---|---|
| Romidepsin and Lenalidomide | Experimental | This will be a multicentered, open label, phase Ib/IIa trial of romidepsin and lenalidomide in patients with relapsed or refractory lymphomas or multiple myeloma. Lenalidomide will be provided in accordance with the Celgene Corporation's Revlimid REMS® program. Per standard Revlimid REMS® program requirements, all physicians who prescribe lenalidomide for research subjects enrolled into this trial, and all research subjects enrolled into this trial, must be registered in, and must comply with, all requirements of the Revlimid REMS® program. Only enough lenalidomide for one cycle of therapy will be supplied to the patient each cycle. Receives: Drug: Romidepsin; Drug: Lenalidomide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Dose Limiting Toxicities/DLTs
The phase Ib portion of the study is designed to determine the MTD of romidepsin and lenalidomide.
Measured: 1 year
Number of Participants Evaluable for AEs
Subjects will be evaluated for AEs at each visit with the NCI CTCAE v4.0 used as a guide for the grading of severity.
Measured: 1 year
Secondary outcomes (3)
Assess the Overall Response Rate (ORR)
Overall response rate (ORR), complete response rate, very good partial response/partial response rate will be summarized using proportions and confidence intervals will be provided. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Measured: 1 year
Complete Response Rate/CRR
CRR is defined as Complete Response Rate. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Measured: 1 year
Assess the Time to Best Response (TTBR)
Duration of response (DOR), and event free survival (EFS). Time to response,duration of response and event free survival will be analyzed by routine survival analysis tools such as Kaplan-Meier estimation or competing risks method. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
Measured: up to 50 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Dec 2012 (estimated)
- Study startDec 2012
- Primary completionOct 2023
- Study completionOct 2023
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.
- Other trials for Multiple MyelomaStudies of the same condition, open and under way.
- More trials run by Memorial Sloan Kettering Cancer 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 49 participants (actual)
Sponsor and investigators
- Lead sponsor
- Memorial Sloan Kettering Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- St. Francis Hospital & Medical Center, Hartford CT, Weill Medical College of Cornell University, University of Nebraska, Celgene Corporation, Biologics, Inc.
- Responsible party
- Sponsor
- Investigators
- Steven Horwitz, MD, Principal investigator, Memorial Sloan Kettering Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01755975
- Sponsor's protocol ID
- 12-170
- Status last verified
- Oct 2023
- First submitted
- 19 Dec 2012
- Last updated
- 7 Nov 2024
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 7 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase Ib/IIa Study of Romidepsin in Combination With Lenalidomide in Adults With Relapsed or Refractory Lymphomas and Myeloma
- ClinicalTrials.gov ID
- NCT01755975
- Acronym / sponsor ID
- 12-170
- Conditions
- Multiple Myeloma, Non-Hodgkin's Lymphoma
- Keywords
- LENALIDOMIDE (CC-5013), Romidepsin (Istodax), 12-170
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 49 participants (actual)
- Lead sponsor
- Memorial Sloan Kettering Cancer CenterUniversity, hospital or other
- Collaborators
- St. Francis Hospital & Medical Center, Hartford CT, Weill Medical College of Cornell University, University of Nebraska, Celgene Corporation, Biologics, Inc.
- Study start
- Dec 2012
- Primary completion
- Oct 2023 (actual)
- Study completion
- Oct 2023 (actual)
- First posted
- 24 Dec 2012 (estimated)
- Results
- Posted 7 Nov 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The treatments used to treat lymphoma and multiple myeloma sometimes do not always work well or they may only work for a short period of time. This is why new treatments are being tested.
This study will test a new combination of two drugs that are already approved by the Food and Drug Administration for treatment of certain kinds of blood cancers. These drugs are romidepsin and lenalidomide. Both these drugs by themselves have been used to treat lymphoma or multiple myeloma. However, while these drugs are routinely used alone, this is the first time they will be tested together. The mechanism of action of both drugs is not well understood but both have been shown to to be effective by themselves in lymphoma and multiple myeloma.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Romidepsin and Lenalidomide | Experimental | Drug: Romidepsin, Drug: LenalidomideThis will be a multicentered, open label, phase Ib/IIa trial of romidepsin and lenalidomide in patients with relapsed or refractory lymphomas or multiple myeloma. Lenalidomide will be provided in accordance with the Celgene Corporation's Revlimid REMS® program. Per standard Revlimid REMS® program requirements, all physicians who prescribe lenalidomide for research subjects enrolled into this trial, and all research subjects enrolled into this trial, must be registered in, and must comply with, all requirements of the Revlimid REMS® program. Only enough lenalidomide for one cycle of therapy will be supplied to the patient each cycle. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (25 listed)
- Pathology confirmed lymphoma or multiple myeloma
- Hodgkin lymphoma is eligible for either phase and will be considered a B-cell lymphoma in the phase IIa study.
- Phase IIa portion, subjects must have B-cell lymphoma, T-cell lymphoma, or multiple myeloma.
- Relapse or progression after at least 1 systemic therapy.
- Measurable disease for phase IIa portion only.
Key exclusion criteria (24 listed)
- 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 lenalidomide or romidepsin).
- Known hypersensitivity to thalidomide.
- The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs.
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 |
|---|---|---|
| RomidepsinRomidepsin will be administered intravenously on days 1, 8, and 15 of a 28-day cycle. | Drug | Romidepsin and Lenalidomide |
| LenalidomideLenalidomide will be taken orally daily for 21 days of a 28-day cycle. | Drug | Romidepsin and Lenalidomide |
Primary outcome
Number of Dose Limiting Toxicities/DLTs
Time frame: 1 year
The phase Ib portion of the study is designed to determine the MTD of romidepsin and lenalidomide.
Number of Participants Evaluable for AEs
Time frame: 1 year
Subjects will be evaluated for AEs at each visit with the NCI CTCAE v4.0 used as a guide for the grading of severity.
3 secondary outcomes
Assess the Overall Response Rate (ORR)
Time frame: 1 year
Complete Response Rate/CRR
Time frame: 1 year
Assess the Time to Best Response (TTBR)
Time frame: up to 50 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Nov 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Memorial Sloan Kettering Cancer CenterLink provided by the sponsor.
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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.
Steven Horwitz, MD principal investigator
Memorial Sloan Kettering Cancer Center
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Romidepsin and Lenalidomide in people with Multiple Myeloma and Non-Hodgkin's Lymphoma, run by Memorial Sloan Kettering Cancer Center at 7 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 25 inclusion and 24 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 7 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 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 combined 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.
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 7 Nov 2024). 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?
Number of Dose Limiting Toxicities/DLTs (time frame: 1 year). The study lists 2 primary outcomes in all. 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 7 Nov 2024.