Trial of Duvelisib in Combination With Either Romidepsin or Bortezomib in Relapsed/Refractory T-cell Lymphomas

Not Recruiting

Trial ID: NCT02783625


The purpose of this study is to test the safety of a study drug called duvelisib.

Official Title

A Phase I Trial of Duvelisib in Combination With Either Romidepsin or Bortezomib in Relapsed/Refractory T-cell Lymphomas

Stanford Investigator(s)

Youn H Kim, MD
Youn H Kim, MD

The Joanne and Peter Haas, Jr., Professor for Cutaneous Lymphoma Research and Professor, by courtesy, of Medicine (Oncology)

Michael Khodadoust
Michael Khodadoust

Assistant Professor of Medicine (Oncology) and of Dermatology


Inclusion Criteria:

   - Pathologically confirmed T-cell lymphomas at the enrolling institution, including
   stage ≥ Ib CTCL, which has relapsed or progressed after at least one systemic therapy.

   - Age ≥ 18

   - Previous systemic anti-cancer therapy must have been discontinued at least 3 weeks
   prior to treatment. For the dose expansion phase, in progressing subjects, a 2 week
   washout may be allowed after discussion with the MSK Principal Investigator.

   - Previous radiation 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 to Grade
   1 or baseline. Lymph node or other diagnostic biopsies within 2 weeks are not
   considered exclusionary.

   ° Patients who have received localized RT as part of their immediate prior therapy may
   be allowed to enroll with shorter washout period after discussion with the MSK
   Principal Investigator.

   - ECOG ≤ 2

   - Meet the following laboratory criteria without use of growth factor support or
   platelet transfusions for 1 week:

   i) Absolute neutrophil count ≥ 1.0 K/mcl, ii) Platelet count ≥ 80 K/μl (in the
   expansion cohorts, if thrombocytopenia is due to bone marrow involvement platelet
   count must be ≥ 50 K/μL), iii) Patients enrolled in the dose escalation phase who are
   not enrolled on the expansion cohorts must have calculated creatinine clearance ≥
   50ml/min by Cockcroft-Gault formula. Patients enrolled in the Dose Expansion phase
   must have calculated creatinine clearance ≥ 40ml/min by Cockcroft-Gault formula.

iv) Total bilirubin ≤ 1.5 x upper limit of normal (ULN) or ≤ 3 x ULN if documented hepatic
involvement with lymphoma, or ≤ 5 x ULN if history of Gilbert's syndrome; AST (SGOT) and
ALT (SGPT) ≤ 3 x ULN; ≤ 5 ULN if due to lymphoma involvement

   - Measurable disease for dose expansion and lead in phase only.

Measurable disease defined by:

   1. Revised International Working Group (Cheson, 2007) Classification for systemic
   lymphoma or

   2. Atypical and or malignant lymphocytes quantifiable by flow cytometry or morphology in

   3. or bone marrow mSWAT > 0 or Sezary couny >/= 1000 cells/ul

      - 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 20 mg of prednisone is

      i) Topical steroids that have been used for > 3 weeks may be continued (CTCL
      only). All other histologies (not CTCL): Topical steroids use is permissible
      without restriction

      - Women of reproductive potential† must have a negative serum or urine β human
      chorionic gonadotropin (βhCG) pregnancy test. All women of reproductive
      potential, all sexually active male patients, and all partners of patients must
      agree to use adequate methods of birth control (e.g. latex condoms) throughout
      the study and for 30 days after the last dose of study drug.

         - 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:

   - 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 the
   study medications).

   - Prior use of duvelisib if discontinued due to toxicity.

   - For the romidepsin arm of the study, prior therapy with romidepsin if discontinued due
   to toxicity.

   - For the bortezomib arm of the study, prior therapy with a proteasome inhibitor if
   discontinued due to toxicity.

   - For the bortezomib arm of the study, patients with grade ≥2 peripheral neuropathy.

   - History of chronic liver disease, veno-occlusive disease, or current alcohol abuse.

   - Administration of a live vaccine within 6 weeks of first dose of study drug.

   - Prior surgery or gastrointestinal dysfunction that may affect drug absorption (e.g.,
   gastric bypass surgery, gastrectomy)

   - Known seropositive and requiring anti-viral therapy for human immunodeficiency virus
   (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV). Subjects with chronic
   hepatitis B or C as defined as test .

   - Subjects with positive Hep B serology. Subjects with a negative HBsAg and a positive
   HBcAb require an undetectable/negative hepatitis B DNA test (e.g., polymerase chain
   reaction [PCR] test) to be enrolled, and will require prophylactic antiviral treatment
   (e.g., F) initiated prior to the first dose of study drug, an continued until
   approximately 6 to 12 months after completion of study drug(s).

   - Patients with positive hepatitis C virus Ab

   - Subjects with active EBV unrelated to underlying lymphoma (positive serology for
   anti-EBV VCA IgM antibody and negative for anti-EBV EBNA IgG antibody, or clinical
   manifestations and positive EBV PCR consistent with active EBV infection.

   - Subject with active CMV (positive serology for anti-CMV IgM antibody and negative for
   anti-CMV IgG antibody and positive CMV PCR with clinical manifestations consistent
   with active CMV infection) and requiring therapy will be excluded from participation
   in the study. Carriers will be monitored per institutional guidelines.

   - Receiving systemic therapy for another primary malignancy (other than T-cell lymphoma)

   - Patients with more than one type of lymphoma may be enrolled after discussion with the
   MSK Principal Investigator.

   - Adjuvant or maintenance therapy to reduce the risk of recurrence of other malignancy
   (other than T-call lymphoma) is permissible after discussion with the MSK Principal

   - Known central nervous system or meningeal involvement (in the absence of symptoms,
   investigation into central nervous system involvement is not required).

   - Uncontrolled infection requiring systemic antimicrobials

   - The following known cardiac abnormalities:

      1. Congenital long QT syndrome.

      2. QTc/QTf interval ≥ 480 milliseconds; unless secondary to pacemaker or bundle
      branch block.

      3. Myocardial infarction within 6 months. (Subjects with a history of myocardial
      infarction within the last 6 to12 months 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.)

      4. Other significant ECG abnormalities including 2nd degree atrio- ventricular (AV)
      block (AV) block type II, 3rd degree AV block.

      5. 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.

      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.

      6. 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.

      7. 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 MUGA,
      echocardiogram, or cardiac MRI.

      8. 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).

      9. Hypertrophic cardiomegaly or restrictive cardiomyopathy from prior treatment or
      other causes.

   10. 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 prior to study registration) and meet all other inclusion

   11. Any cardiac arrhythmia requiring an anti-arrhythmic medication (excluding stable
      doses of beta-blockers)

   12. For patients enrolling on the Romidepsin arm; taking drugs associated with
      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). Caution should be used when administering study drugs to patients
      taking medications significantly metabolized by these enzymes refer to
      ( 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.


drug: Romidepsin

drug: Bortezomib

drug: duvelisib

Not Recruiting

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Sophia Fong

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