Recurrent Waldenstrom Macroglobulinemia, Refractory Waldenstrom Macroglobulinemia
Conditions
Brief summary
This phase I trial studies the side effects and best dose of pomalidomide in treating patients with Waldenstrom macroglobulinemia that has returned after a period of improvement (relapsed) or does not respond to treatment (refractory). Pomalidomide may stimulate the immune system in different ways and stop cancer cells from growing.
Detailed description
PRIMARY OBJECTIVES: I. To determine the maximum tolerated dose (MTD) of pomalidomide in patients with relapsed or refractory Waldenstrom macroglobulinemia. SECONDARY OBJECTIVES: I. To evaluate the safety and toxicity profile of pomalidomide in patients with relapsed or refractory Waldenstrom macroglobulinemia. II. To evaluate the efficacy of pomalidomide in patients with relapsed or refractory Waldenstrom macroglobulinemia. OUTLINE: This is a dose-escalation study. Patients receive pomalidomide orally (PO) on days 1-28 or 1-21. Courses repeat every 21 or 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 6 months.
Interventions
DRUGPomalidomide
Given PO
Sponsors
National Cancer Institute (NCI)
M.D. Anderson Cancer Center
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
* Understand and voluntarily sign an informed consent form * Able to adhere to the study visit schedule and other protocol requirements * Waldenstrom's macroglobulinemia that has relapsed and/or is refractory to at least one prior line of therapy * All previous cancer therapy, including radiation, hormonal therapy and surgery, must have been discontinued at least 4 weeks prior to treatment in this study * Eastern Cooperative Oncology Group (ECOG) performance status of =\< 2 at study entry * Serum creatinine =\< 2.0 mg/dL * Creatinine clearance \>= 45 ml/min * Total bilirubin =\< 3 x upper limit of normal (ULN) or direct bilirubin =\< 2 x ULN * Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2 x ULN * Platelet count \>= 20 K/microL * Absolute neutrophil count \>= 500 K/microL * 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 to 14 days prior to and again within 24 hours of starting pomalidomide 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 pomalidomide; FCBP must also agree to ongoing pregnancy testing; men must agree to practice complete abstinence or agree use a latex condom during sexual contact with a FCBP while participating in the study, during dose interruptions and for at least 90 days following study drug discontinuation, even if they have had a successful vasectomy; all patients must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure * Able to take aspirin (325 mg) daily as prophylactic anticoagulation (patients intolerant to acetylsalicylic acid \[ASA\] may use therapeutic dose warfarin or low molecular weight heparin) * All study participants must be registered into the mandatory POMALYST REMS program, and be willing and able to comply with the requirements of the POMALYST REMS program
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; (lactating females must agree not to breast feed while taking pomalidomide or for 28 days after stopping pomalidomide) * Any medical or psychiatric 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 the first dose of study drug * Known hypersensitivity to thalidomide or lenalidomide * The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs * Any prior use of pomalidomide * Concurrent use of other anti-cancer agents or treatments * Known positive for human immunodeficiency virus (HIV) or acute hepatitis A or acute or chronic active hepatitis B or C * Grade \> 2 peripheral neuropathy * Neutrophil count \< 1000 K/microL and/or * Platelet count \< 100 K/microL unless infiltration by Waldenström's macroglobulinemia equals or exceed 60% of bone marrow cellularity
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients Experiencing MTD | Participants Experiencing Study Medication Maximum Tolerated Dose through Study Completion (Avg. 1 Year) | Maximum Tolerated Dose |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cycles Completed | Study Completion (Avg. 1 Year) | Length of Treatment |
| Changes in Waldestrom Biomarkers | Through Study Completion (Avg. 1 Year) | Average Paraprotein1 gm/dL Change Cycle 1 thru Study |
Countries
United States
Participant flow
Recruitment details
Patient Eligibility:Waldenstrom relapsed,\>/18 - years old,ECOG \<\ 2,Labs NCS,no prior cancers,females not preganant,\ 1\> line(s) prior therapy, no therapy in 4 weeks. Excluded:pregnant, breast-feeding, serious diagnosis,chemotherapy reaction,prior pomalidomide,HIV/ Hepatitis A-C +,concurrent chemotherapy,grade\ \>2 neuropathy,andANC count \<\ 1000K/ul.
Pre-assignment details
Six patients were screen failures; did not meet inclusion criteria. Original study design included Arms with assignment to increasing dose escalation including 3 and 4mg Pomolidomide Arms/Cohorts; however, safety concerns early on regarding Dose Limiting Toxicities for 2mg Cohort compelled omitting the 3 and 4mg Arms/Cohorts.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 2 2mg Pomolidomide per day per Cycle (Cycle = 28 days) | 3 |
| Cohort 3 1mg Pomolidomide per day per Cycle (Cycle = 28 days) | 6 |
| Total | 9 |
Baseline characteristics
| Characteristic | Cohort 3 | Total | Cohort 2 |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 4 Participants | 2 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants | 5 Participants | 1 Participants |
| Age, Continuous | 66 years STANDARD_DEVIATION 11 | 66 years STANDARD_DEVIATION 11 | 67 years STANDARD_DEVIATION 10 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 6 Participants | 9 Participants | 3 Participants |
| Region of Enrollment United States | 6 participants | 9 participants | 3 participants |
| Sex: Female, Male Female | 1 Participants | 2 Participants | 1 Participants |
| Sex: Female, Male Male | 5 Participants | 7 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 6 |
| other Total, other adverse events | 3 / 3 | 6 / 6 |
| serious Total, serious adverse events | 3 / 3 | 1 / 6 |
Outcome results
Primary
Number of Patients Experiencing MTD
Maximum Tolerated Dose
Time frame: Participants Experiencing Study Medication Maximum Tolerated Dose through Study Completion (Avg. 1 Year)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 2 | Number of Patients Experiencing MTD | 1 Participants |
| Cohort 3 | Number of Patients Experiencing MTD | 5 Participants |
Secondary
Changes in Waldestrom Biomarkers
Average Paraprotein1 gm/dL Change Cycle 1 thru Study
Time frame: Through Study Completion (Avg. 1 Year)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 2 | Changes in Waldestrom Biomarkers | 0.3 Paraprotein #1 gm/dL | Standard Deviation 0.1 |
| Cohort 3 | Changes in Waldestrom Biomarkers | 1.4 Paraprotein #1 gm/dL | Standard Deviation 0.7 |
Secondary
Changes in Waldestrom Biomarkers
Average Reduction in IgM Protein mg/dL from Cycle 1 thru Study
Time frame: Through Study Completion (Avg. 1 Year)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 2 | Changes in Waldestrom Biomarkers | 493 IgM Protein mg/dL | Standard Deviation 955 |
| Cohort 3 | Changes in Waldestrom Biomarkers | 1252 IgM Protein mg/dL | Standard Deviation 2011 |
Secondary
Cycles Completed
Length of Treatment
Time frame: Study Completion (Avg. 1 Year)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 2 | Cycles Completed | 2 Number of Cycles |
| Cohort 3 | Cycles Completed | 7 Number of Cycles |