Pomalidomide, Dexamethasone and Rituximab in Waldenstrom's Macroglobulinemia

Phase 1

Terminated

Brief Summary: Pomalidomide is a newly discovered drug that may stop cancer cells from growing abnormally. Pomalidomide may also stimulate the immune system to fight the cancer cells and possibly improve the effectiveness of dexamethasone and rituximab to fight the Waldenstrom's Macroglobulinemia (WM) cancer cells. This drug have been used in multiple myeloma and information from these other research studies suggests that Pomalidomide may help to reduce or prevent the growth of cancer cells.

Detailed Description: * Participants will be given a study drug-dosing calendar for each treatment cycle. Each treatment cycle lasts 28 days during which time participants will take Pomalidomide orally once a day. Dexamethasone and rituximab will be administered intravenously on weeks 1, 2, 3, 4 and on weeks 12, 13, 14, 15.

* Since we are looking for the highest dose of Pomalidomide in combination with dexamethasone and rituximab which can be administered safely without severe or unmanageable side effects, not everyone who participates will receive the same dose of the study drug. The dose participants will get will depend on the number of participants who have been enrolled in the study and how well they have tolerated their doses.

* As long as there is no evidence that the participant's Waldenstrom's Macroglobulinemia has progressed, they can continue to receive Pomalidomide for up to 52 weeks. Participants will be asked to return to the clinic for follow-up tests at least every three months for four years.

Recruitment & Eligibility

Inclusion Criteria

18 years of age or older
Able to adhere to the study visit schedule and other protocol requirements
Clinicopathological diagnosis of Waldenstrom's macroglobulinemia using consensus panel criteria
CD20 positive based on any previous performed bone marrow immunohistochemistry or flow cytometric analysis
Meet criteria to treat based on consensus panel criteria
Patient must have received at least one previous therapy for WM
All previous cancer therapy, including radiation, hormonal therapy and surgery, must have been discontinued at least 4 weeks prior to treatment in this study
Measurable disease, defined as presence of immunoglobulin M (IgM) paraprotein with a minimum IgM level of 2 times (or greater) the upper limit of each institution's normal value is required
ECOG Performance status of 0, 1 or 2
Laboratory tests within ranges outlined in the protocol
Disease free of prior malignancies for 5 years or more with exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma in situ of the cervix or breast
Screening of patients at high risk of HBV or HCV infection
Willing and able to take aspirin or alternate prophylactic anticoagulants

Exclusion Criteria

Any serious medical condition, laboratory abnormality, or psychiatric illness
Pregnant or lactating females
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
Resistance or intolerance to prior rituximab therapy
Previous therapy with thalidomide or lenalidomide
Known hypersensitivity to thalidomide, lenalidomide or pomalidomide
The development of erythema nodosum if characterized by a desquamating rash while taking similar drugs
Concurrent use of other anti-cancer agents or treatments
History of non-compliance to medical regimens
Patients unwilling to or unable to comply with the protocol
Known positive for HIV or hepatitis infection
Any history of CVA (Cerebral Vascular Accident/stroke) or clots
Active DVT or PE that has not been therapeutically anticoagulated
NYHA classification III and greater heart failure
Any patient that is unable to ingest or process pomalidomide

Arm && Interventions

Group	Intervention	Description
pomalidomide, dexamethasone, rituximab	rituximab	Drug: pomalidomide Taken orally once a day Drug: dexamethasone Given intravenously on weeks 1, 2, 3 and 4 and weeks 12, 13, 14 and 15 Drug: rituximab Given intravenously on weeks 1, 2, 3 and 4 and weeks 12, 13, 14 and 15
pomalidomide, dexamethasone, rituximab	dexamethasone	Drug: pomalidomide Taken orally once a day Drug: dexamethasone Given intravenously on weeks 1, 2, 3 and 4 and weeks 12, 13, 14 and 15 Drug: rituximab Given intravenously on weeks 1, 2, 3 and 4 and weeks 12, 13, 14 and 15
pomalidomide, dexamethasone, rituximab	pomalidomide	Drug: pomalidomide Taken orally once a day Drug: dexamethasone Given intravenously on weeks 1, 2, 3 and 4 and weeks 12, 13, 14 and 15 Drug: rituximab Given intravenously on weeks 1, 2, 3 and 4 and weeks 12, 13, 14 and 15

Primary Outcome Measures

Name	Time	Method
Maximum Tolerated Dose of Pomalidomide	2 years	To determine the MTD of pomalidomide administered orally in patients with Waldenstrom's Macroglobulinemia in combination with dexamethasone and rituximab. Because maximum tolerated dose was not determined due to study termination, the highest dose of pomalidomide administered is presented below.
Tolerability of Pomalidomide	2 years	Number of participants with dose limiting toxicities which resulted in being removed from pomalidomide therapy

Secondary Outcome Measures