An Open Label, International, Multi-centre, Phase I/IIa Study of Lenalidomide (Revlimid) and Romidepsin (Istodax) for Relapsed /Refractory Hodgkin Lymphoma, Mature T-cell Lymphoma and Multiple Myeloma. (RId Study)

Inclusion Criteria:

1. All patients must have a biopsy-proven diagnosis of one of the following malignancies
that meets the additional disease-specific inclusion criteria.

A. Mature T-Cell lymphoma. The following entities are eligible. PTCL or CTCL
(including MF and SS) but excluding adult T-cell leukemia/lymphoma, primary cutaneous
CD30+ lymphoma, lymphomatoid papulosis, and NK or LGL leukemia.(The complete WHO
classification of T-cell lymphoma can be found in the appendices).

1. Peripheral T-cell lymphoma: patients must have relapsed or progressed after: at
least one prior chemotherapy-based treatment, or not suitable for a conventional
chemotherapeutic approach as judged by the investigator.

2. Sezary syndrome/ Mycosis Fungoides: patients must have relapsed or progressed
after at least one prior systemic therapy.

B. Hodgkin lymphoma

1. At least one prior chemotherapy-based treatment.

2. Prior autograft in those eligible for autologous transplantation according to
institutional guidelines.

C. Myeloma

1. Relapsed after at least one prior systemic therapy that includes thalidomide
(unless intolerant or contraindicated) or lenalidomide. Those who have received
prior lenalidomide must have had a response that exceeded 6 months.

2. Patients who are candidates for autologous stem cell transplant in first
remission are not eligible.

3. Patients must have failed/relapsed after bortezomib therapy.

2. ECOG performance status <2

3. Age >18 years.

4. Life expectancy ≥90 days.

5. Patients must have normal organ and marrow function as defined below:

absolute neutrophil count >1.0 x109/L (or greater than 0.75x109/L if >50% plasma
cells or >50% lymphoma in the bone marrow) Neutrophil count must not be supported by
G-CSF prior to study entry. platelets >100 x109/L (or >75 x 109 if >50% plasma
cells or >50% lymphoma in the bone marrow).

(Transfusion to achieve these goals would not qualify the patient) total bilirubin
<1.5x the institutional upper limit of normal. (<2.5x for Gilbert's disease).

AST(SGOT)/ALT(SGPT) <2.5 X institutional upper limit of normal

Creatinine clearance >60 mL/min/1.73 m2 in the dose escalation phase, and >30
mL/min/1.73 m2 in phase II.

Serum potassium & magnesium Serum potassium ≥3.8 mmol/L Serum magnesium ≥1.8mg/dL
/0.75mmol/L (supplementation is allowed)

6. Females of childbearing potential (FCBP) must have a negative serum or urine
pregnancy test with a sensitivity of at least 50 mIU/mL within 10 - 14 days and again
within 24 hours prior to prescribing lenalidomide for Cycle 1 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.

Exclusion Criteria:

1. Patients receiving any other investigational agents within 4 weeks.

2. Patients who have had chemotherapy or radiotherapy within 4 weeks prior to entering
the study or those who have not adequately recovered from grade III/IV adverse events
due to agents administered more than 4 weeks earlier.

3. Prior exposure to lenalidomide, in patients with myeloma, except if a response
(including stable disease) was maintained for at least 6 months. (Washout period of 4
weeks required)

4. Prior treatment with HDAC inhibitor (not including sodium valproate for neurological
or psychiatric disorders), except if response (including stable disease) was
maintained for at least 3 months. (Washout period of 4 weeks required)

5. Concomitant treatment with sodium valproate (washout 4 weeks required).

6. Central nervous system involvement by lymphoma or myeloma.

7. A history of allergic reaction to romidepsin or lenalidomide, boron or mannitol.

8. A history of Gr III/IV drug-related non-hematological toxicity, excluding
thromboembolism or sepsis, in a prior exposure to either lenalidomide or a histone
deacetylase inhibitor.

9. Concomitant corticosteroid except for patients on a stable dose of ≤10mg
prednisone/day for at least 4 weeks prior to screening.

10. Congenital long QT syndrome, or a QTc interval >450 milliseconds

11. Patients who have had a myocardial infarction within twelve months of study entry.

12. Patients who have active coronary artery disease (for example NYHA class II or above
angina).

Any patient in whom coronary artery disease is suspected should be referred for a
cardiology consultation and if active myocardial ischemia is demonstrated, the
patient should be excluded. If a non-invasive imaging study is equivocal, it may be
necessary to proceed to coronary angiography.

13. Patients with a baseline ECG showing evidence of cardiac ischaemia (ST depression of
≥2mm)

14. Patients with NYHA-class congestive heart failure ≥II

15. Patients with cardiac ejection fraction less than the institutional lower limited of
normal by a gated heart-pool scan, or echocardiogram.

16. Patients with a history of sustained VT, VF, torsade de pointes or cardiac arrest
unless that issue is currently managed with an implantable cardioverter defibrillator
(AICD).

17. Patients with a cardiomyopathy of any cause.

18. Patients with uncontrolled hypertension ie. SBP ≥160mmHg or DBP ≥95mmHg

19. Patients with cardiac arrythmia requiring anti-arrythmic medication other than a beta
blocker or calcium channel blocker. Patients in who digitalis can not be
discontinued are excluded from the study.

20. Patients with mobitz-II second degree heart block that do not have a pacemaker.

1. Patients with first degree or Mobitz-I second degree block, bradyarrhythmia or
sick sinus syndrome require holter monitoring and evaluation for eligibility by
a cardiologist.

2. Patients with other cardiac disease may be excluded at the discretion of the PI
following consultation with a cardiologist.

21. Patients who require concomitant use of drugs known to cause significant prolongation
of the QT interval.

22. Patients who require concomitant use of warfarin, due to potential for drug
interaction.

23. Pregnancy in female patients. Lactating females must agree not to breast feed while
taking lenalidomide.

24. Patients with known HIV infection.

25. Patients with known Hepatitis B infection.

26. Prior allotransplantation, unless the patient has been completely weaned off
immunosuppressive agents for ≥3 months.

27. Myeloma, patient who is a candidate for autologous stem cell transplant

28. Pre-existing motor or sensory neuropathy ≥ grade 3.

29. Other serious and / or uncontrolled medication condition

30. Prior diagnosis of cancer that was:

1. more than 3 years prior to current diagnosis with estimated clinical expectation
of progression greater than 10% within next 2 years.

2. within 3 years of current diagnosis with the exception of successfully treated
basal cell or squamous cell skin carcinoma, carcinoma in situ of the cervix or
localised cancer treated curatively with local therapy only.