Lenalidomide and Pidilizumab in Treating Patients With Relapsed or Refractory Multiple Myeloma

PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose (MTD), safety and efficacy of CT-011 (pidilizumab)
in combination with lenalidomide (Revlimid) and assess efficacy in terms of overall response
rate in patients with relapse/refractory multiple myeloma (MM).

OUTLINE: This is a phase I, dose-escalation study followed by a phase II study.

Patients receive lenalidomide orally (PO) daily on days 1-21 and pidilizumab intravenously
(IV) over 2 hours on day 3. Courses repeat every 28 days in the absence of disease
progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days.

Inclusion Criteria:

- Patients have evidence of relapse or refractory disease as defined by International
Myeloma Working Group (IMWG) criteria and measurable disease as defined by any of the
following:

- Serum M-protein >= 0.5 g/dl (>= 10 g/l)

- Urine monoclonal protein >= 200 mg/24h

- Involved free light chain (FLC) level >= 10mg/dl (>= 100mg/l) and an abnormal
serum free light chain ratio (< 0.26, or > 1.65)

- Measurable biopsy proven plasmacytoma (should be measured within 28 days of
initial investigational agent dosing)

- Patients must have had at least 2 prior line of therapy

- Patients must not have had progression of disease on lenalidomide 25 mg; stable
disease on lenalidomide is permitted

- Patient may be enrolled at any time from last line of therapy

- Absolute neutrophil count (ANC) > 1000/uL

- Platelets >= 75,000/uL, if plasma cell percentage on bone marrow biopsy aspirate or
core is > 30%, platelet eligibility requirement will be adjusted to 60,000/uL

- Total bilirubin =< 1.5 mg/dL

- Alkaline phosphatase =< 3 X the upper limit of normal (ULN)

- Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2 X the ULN

- Serum creatinine =< 2 mg/dL or calculated creatinine clearance of >= 40 ml/min within
14 days of registration using Modification of Diet in Renal Disease (MDRD) formula

- Patient must be able to swallow capsule or tablet

- Patients must provide informed consent

- Patients must have a left ventricular ejection fraction > 30%, no uncontrolled
arrhythmias or New York Heart Association class III-IV heart failure

- Patients must have a Karnofsky performance status >= 70

- A negative pregnancy test will be required for all women of child bearing potential;
breast feeding is not permitted

- Fertility requirements:

- Female patients with child bearing potential must have a negative pregnancy test
at least 7 days before starting treatment drugs

- Male patients must agree to use an adequate method of contraception for the
duration of the study and for 90 days afterwards

- Female patients must be either posy-menopausal, free from menses >= 2 years
(yrs), surgically sterilized, willing to use two adequate barrier methods of
contraception to prevent pregnancy, or agree to abstain from sexual activity
starting from screening and for 90 days afterwards

- Female patients of child bearing potential must agree to comply with the
fertility and pregnancy test requirements dictated by the Rev-Assist program

Exclusion Criteria:

- Patients with peripheral neuropathy > Common Terminology Criteria for Adverse Events
(CTCAE) grade 2

- Prior exposure to anti programmed cell death 1 (PD1) or anti programmed cell death 1
ligand 1 (PDL1)

- Patients receiving concurrent corticosteroids at the time protocol therapy is
initiated other than for physiologic maintenance treatment

- History of allergic reaction (including erythema nodosum) to lenalidomide

- Concurrent use of complementary or alternative medicines that would confound the
interpretation of toxicities and antitumor activity of the study drugs

- Patients with contraindication to thromboprophylaxis

- Unacceptable cardiac risk factors defined by any of the following criteria: patients
with congenital long QT syndrome, any history of ventricular fibrillation or torsade
de pointes, bradycardia defined as heart rate (HR) < 50 bpm, left ventricular ejection
fraction < 30%

- Patients who have received targeted or investigational agents within 2 weeks or within
5 half-lives of the agent and active metabolites (whichever is longer) and who have
not recovered from side effects of those therapies

- Patients who have undergone major surgery =< 2 weeks prior to starting study drug or
who have not recovered from the side-effects of surgery

- Patients with known positivity for human immunodeficiency virus (HIV), or hepatitis C;
baseline testing for HIV and hepatitis C is not required

- Patients with a history of another primary malignancy that is currently clinically
significant or currently requires active intervention, other than non-melanoma skin
cancer and carcinoma in situ of the cervix should not be enrolled; patients are not
considered to have a "currently active" malignancy if they have completed therapy for
a prior malignancy, are disease free from a prior malignancy for >= 5 yrs and are
considered by their physician to be less than 30% risk of relapse

- Patients with active (untreated or relapsed) central nervous system (CNS) metastasis
of the patient's myeloma

- Patients with a history of gastrointestinal surgery or other procedure that might, in
the opinion of the investigator(s), interfere with the absorption or swallowing of the
study drugs

- Patients with any significant history of non-compliance to medical regimens or
unwilling or unable to comply with the instructions given to them by the study staff

- Any other medical condition, including mental illness or substance abuse, deemed by
the investigator(s) to likely interfere with the patient's ability to sign informed
consent, cooperate and participate in the study, or interfere with the interpretation
of the results