Waldenstrom's Macroglobulinemia
Conditions
Keywords
WM, pomalidomide, dexamethasone, rituximab
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.
Interventions
DRUGpomalidomide
Taken orally once a day
DRUGdexamethasone
Given intravenously on weeks 1, 2, 3 and 4 and weeks 12, 13, 14 and 15
DRUGrituximab
Given intravenously on weeks 1, 2, 3 and 4 and weeks 12, 13, 14 and 15
Sponsors
Celgene Corporation
Steven P. Treon, MD, PhD
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
United States
Participant flow
Recruitment details
A total of 7 participants were recruited at the DFCI medical clinic between 9/22/2010 and 4/3/2012.
Participants by arm
| Arm | Count |
|---|---|
| Pomalidomide, Dexamethasone, 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: Taken orally once a day
dexamethasone: Given intravenously on weeks 1, 2, 3 and 4 and weeks 12, 13, 14 and 15
rituximab: Given intravenously on weeks 1, 2, 3 and 4 and weeks 12, 13, 14 and 15 | 7 |
| Total | 7 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 3 |
Baseline characteristics
| Characteristic | Pomalidomide, Dexamethasone, Rituximab |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 3 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants |
| Age, Continuous | 64 years STANDARD_DEVIATION 7.27 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 7 Participants |
| Region of Enrollment United States | 7 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 7 / 7 |
| serious Total, serious adverse events | 3 / 7 |
Outcome results
Primary
Maximum Tolerated Dose of Pomalidomide
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.
Time frame: 2 years
Population: The maximum tolerated dose was not determined due to study termination. Three participants experienced IgM flare causing them to be removed from the study early.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pomalidomide, Dexamethasone, Rituximab | Maximum Tolerated Dose of Pomalidomide | 1 mg |
Primary
Tolerability of Pomalidomide
Number of participants with dose limiting toxicities which resulted in being removed from pomalidomide therapy
Time frame: 2 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pomalidomide, Dexamethasone, Rituximab | Tolerability of Pomalidomide | 3 participants |