Pomalidomide in Gene Expression Profiling (GEP)-Defined High-risk Multiple Myeloma

Study Overview
=================
Brief Summary
-----------------
This is a phase II study, open-label, single institution trial of pomalidomide in GEP-defined, high-risk relapsing/refractory multiple myeloma. Prior therapy must have included lenalidomide. Patient accrual is 30 over a 2 year period. Primary objective: To determine progression-free survival (PFS) after initiation of pomalidomide therapy Secondary objective: To determine the response rate (CR, n-CR, VGPR) and duration of response after pomalidomide therapy. To determine gene expression profiling (GEP) changes exerted within 48 hours of initiation of daily pomalidomide dosing. To determine gene expression profiling (GEP) changes exerted within 48 hours of initiation 3 concurrent days of exposure to lenalidomide. To determine MRI- and PET-CT-defined CR in studies obtained at baseline and every 6 month examinations.

Detailed Description
-----------------
Pomalidomide is a 2nd generation immunomodulatory agent (IMiD®) with greater efficacy than lenalidomide and with a similar toxicity spectrum. Phase I trials have shown that pomalidomide 1 to 5 mg is well-tolerated1,2. TT3 has been remarkably successful in the management of newly diagnosed MM, inducing CR rates of >60% and 4-year estimates of overall and event-free survival of 85% and 75%. Of those achieving CR, estimated 4-year CR rate is 85%. TT3 maintenance has been with either VTD in 2003-33 or VRD in 2006-66, so that pomalidomide's role in overcoming refractoriness to lenalidomide can be assessed. Pharmacogenomic investigations comparing GEP data obtained at baseline and 48hr post-treatment have been performed in case of thalidomide, dexamethasone, lenalidomide, bortezomib and melphalan3. Thus, as most patients on TT3 had baseline and 48-hr GEP investigations performed after bortezomib, the opportunity exists to investigate, at the time of relapse, not only a re-challenge with bortezomib with 48hr GEP but also pomalidomide's effect. This is a phase II study, open-label, single institution trial of pomalidomide in GEP-defined, high-risk relapsing/refractory multiple myeloma. Prior therapy must have included lenalidomide.

Official Title
-----------------
Phase II Trial of Pomalidomide in GEP-defined High-risk Multiple Myeloma That is Relapsing or Refractory to Prior Therapy

Conditions
-----------------
Multiple Myeloma

Intervention / Treatment
-----------------
* Drug: Pomalidomide


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Participant has multiple myeloma, relapsed or resistant to prior therapy. Participant has high-risk disease, as defined by any of the following: GEP risk score of > 0.66 OR Metaphase based abnormalities of 1q or 1p OR LDH > 360 U/L Participant has received prior therapy with lenalidomide-containing regimen and has been determined to be refractory, resistant, or relapsed. Participant has no significant peripheral neuropathy (< grade 3 by the most current NCI CTCAE version) Participant has adequate hematopoietic reserve as defined by platelet count ≥ 50,000/µL and ANC of > 1000/µL. Participant has adequate renal function as defined by serum creatinine < 2 mg/dL. Participant has adequate hepatic function, defined by serum Total bilirubin </= 1.5 mg/dL and AST (SGOT) and ALT (SGPT) </= x ULN. Participant is 18 years of age or greater. Participant has not received anti-cancer therapy within 4 weeks prior to treatment on this study. Zubrod ≤ 2, unless solely due to symptoms of MM-related bone disease. Disease free of prior malignancies for >/= 5 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma in situ of the cervix or breast. Females of childbearing potential (FCBP)† must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL within 10 - 14 days prior to and again within 24 hours prior to starting lenalidomide or CC-4047 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 or CC-4047. All patients must be informed of the investigational nature of this study and must sign and give written voluntary consent in accordance with institutional and federal guidelines. Willing and able to take aspirin or alternate prophylactic anticoagulation. Exclusion Criteria: Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form. Pregnant or breast feeding females. Men unwilling to use a condom (even if they have undergone a prior vasectomy) while having intercourse with any woman, while taking the drug and for 4 weeks after stopping treatment. Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study. Use of any other experimental drug or therapy within 28 days of baseline. Known hypersensitivity to lenalidomide. The development of erythema nodosum if characterized by a desquamating rash while taking lenalidomide, CC-4047 or similar drugs. Any prior use of CC-4047. Concurrent use of other anti-cancer agents or treatments. Known seropositive for or active viral infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV). Patients who are seropositive because of hepatitis B virus vaccine are eligible. Active malignancy (exception of non melanoma skin cancer or in situ cervical or breast cancer). Active DVT or PE that has not been therapeutically anticoagulated. ≥ grade 3 peripheral neuropathy.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pomalidomide<br> | Drug: Pomalidomide<br>* Only enough CC-4047 for 1 cycle of therapy may be provided to the patient each cycle. Participants will receive CC-4047 4 mg/day for 21 days, every 28 days. Treatment will continue until disease recurrence or untoward toxicity.<br>* Other names: CC-4047;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival (PFS) After Initiation of Pomalidomide Therapy | Progression -free survival (PFS) after initiation of pomalidomide therapy. Progressive disease is defined as increase of > 25% from lowest response value in any one or more of the following: Serum M-component and/or (the absolute increase must be > 0.5 g/dL); Urine M-component and/or (the absolute increase must be > 200 mg/24 h); Only in patients without measurable serum and urine M-protein levels; the difference between involved and uninvolved FLC levels. The absolute increase must be > 10 mg/dL; Bone marrow plasma cell percentage; the absolute percentage must be > 10%; Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas; Development of hypercalcaemia (corrected serum calcium > 11.5 mg/dL or 2.65 mmol/L) that can be attributed solely to the plasma cell proliferative disorder. | 1 year following initiation of pomalidomide therapy | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
relapsed, Pomalidomide, multiple myeloma