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A Phase Ib/IIa Study of Romidepsin in Combination With Lenalidomide in Adults With Relapsed or Refractory Lymphomas and Myeloma

Phase 1/Phase 2
18 Years
Open (Enrolling)
Multiple Myeloma, Non-Hodgkin's Lymphoma

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Trial Information

A Phase Ib/IIa Study of Romidepsin in Combination With Lenalidomide in Adults With Relapsed or Refractory Lymphomas and Myeloma

Inclusion Criteria:

- 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

- 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.

- Multiple myeloma: measurable M protein.

- 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

- 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

- 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 RevAssist® program, and
be willing and able to comply with the requirements of RevAssist®.

- Females of childbearing potential (FCBP)† must have a negative serum pregnancy test
with a sensitivity of at least 25 mIU/mL within 10 - 14 days and again within 24
hours prior to prescribing lenalidomide for Cycle 1 (prescriptions must be filled
within 7 days) and must either commit to continued abstinence from heterosexual
intercourse or begin TWO acceptable methods of birth control, one highly effective
method and one additional effective method AT THE SAME TIME, at least 28 days before
she starts taking lenalidomide. FCBP must also agree to ongoing pregnancy testing.
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

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
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.

- 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).

- 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 are eligible in phase IIa after discussion with prinicipal 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

- 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

- 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.

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

define the maximum tolerated dose

Outcome Description:

The phase Ib portion of the study is designed to determine the MTD of romidepsin and lenalidomide.

Outcome Time Frame:

1 year

Safety Issue:


Principal Investigator

Steven Horwitz, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Memorial Sloan-Kettering Cancer Center


United States: Institutional Review Board

Study ID:




Start Date:

December 2012

Completion Date:

December 2015

Related Keywords:

  • Multiple Myeloma
  • Non-Hodgkin's Lymphoma
  • Romidepsin (Istodax)
  • 12-170
  • Lymphoma
  • Lymphoma, Non-Hodgkin
  • Multiple Myeloma
  • Neoplasms, Plasma Cell



Memorial Sloan Kettering Cancer Center New York, New York  10021
Weill Cornell Medical Center New York, New York  10021
Saint Francis/Mount Sinai Regional Cancer Center Hartford, Connecticut  06105