Waldenstrom's Macroglobulinemia
Conditions
Keywords
everolimus, RAD001, WM
Brief summary
The purpose of this research study is to determine the safety of RAD001(Everolimus) and the highest dose of this drug that can be given to people safely. RAD001(Everolimus) is a drug that works by preventing cells in the body from growing and dividing. Information from basic and Phase I clinical research studies suggests that RAD001 also may help to prevent tumor growth in people with relapsed or refractory lymphoma.
Detailed description
* Participants will take RAD001 orally once a day in the morning. Each treatment cycle lasts for four weeks. Participants will receive up to 72 cycles of treatment. * During each cycle, participants will be asked to visit the clinic for scheduled tests and exams. They will visit the clinic on the first day of each of the first three cycles, and then once every 3 cycles. During the visits, participants will have a physical exam and blood tests.. Participants may also have CT scans of the chest, abdomen and pelvis as well as a bone marrow aspirate and biopsy.
Interventions
DRUGRAD001
Taken orally once a day
Sponsors
Brigham and Women's Hospital
Novartis
Dana-Farber Cancer Institute
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 * Adequate liver and renal function as outlined in the protocol * Fasting serum cholesterol 300mg/dl or less OR 7.75mmol/L or less AND fasting triglycerides 2.5 x institutional ULN or less. * Clinicopathological diagnosis of Waldenstrom's macroglobulinemia as defined by consensus panel of the Second International Workshop on Waldenstrom's macroglobulinemia * No previous therapy for WM * Measurable disease, defined as presence of immunoglobulin M (IgM) paraprotein with a minimum IgM level of 2 times the upper limit of each institution's normal value or greater is required * ECOG Performance status of 0-2 * Patients must have a life expectancy of at least 3 months * Baseline platelet and absolute neutrophil as outlined in the protocol * INR and PTT 1.5 x normalized ratio or less * A male subject agrees to use an acceptable method for contraception for the duration of study and for 8 weeks after the last dose of the study drug * Female subject either post-menopausal or surgically sterilized or willing to use acceptable methods of birth control for the duration of the study and for 8 weeks after the last dose of study drug
Exclusion criteria
* Patients experiencing symptomatic hyperviscosity and requiring plasmapheresis. This includes any patient who, in the judgement of the investigator requires urgent response and will not be eligible. These patients have hyperviscosity which includes serum IgM levels of 5000 mg/dL or greater. Symptoms may include nosebleeds, visual complications, fatigue, headaches, confusion, etc. * Patients, who have had a major surgery or significant traumatic injury within 4 weeks of start of study drug, patients who have not recovered from the side effects of any major surgery or patients that may require major surgery during the course of the study. * Patients receiving chronic, systemic treatment with corticosteroids or another immunosuppressive agent. Topical or inhaled corticosteroids are allowed. * Patients should not receive any immunization with attenuated live vaccines within one week of study entry or during study period. * Patients who have had any severe and/or uncontrolled medical conditions or other conditions that would affect their participation in the study. * Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of RAD001. * Female patients that are pregnant or breast feeding, or adults of reproductive potential who are not using effective birth control methods. * Patients with known hypersensitivity to RAD001 or other rapamycins or to its excipients * Patients with other malignancies within the past 3 years except for adequately treated carcinoma of the cervix or basal or squamous cell of the skin * Patients with known history of HIV seropositivity * History of noncompliance to medical regimens * Patients unwilling to or unable to comply with the protocol
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate of RAD001 in Patients With Previously Untreated WM | End of Treatment, an average of 16 months | Overall Response = Complete Response + Near Complete Response + Very Good Partial Response + Partial Response + Minor Response Complete Response: resolution of all symptoms, normalization of serum IgM levels with complete disappearance of IgM paraprotein by immunofixation, and resolution of any adenopathy or splenomegaly. A near CR (nCR) is defined as fulfilling all CR criteria in the presence of positive immunofixation test for an IgM paraprotein. Very Good Partial Response: \> 90% reduction in serum IgM levels. Partial Response: \> 50% reduction in serum IgM levels. Minor Response: 25-49% reduction in serum IgM levels Progressive Disease: greater than 25% increase in serum IgM level occurs from the lowest attained response value or progression of clinically significant disease related symptom(s). Stable Disease: \< 25% change in serum IgM levels, in the absence of new or increasing adenopathy or splenomegaly and/or other progressive signs or symptoms of WM |
| Time to Progression With Single Agent RAD001 Therapy in Previously Untreated WM. | End of Treatment, an average of 16 months | Progression is defined as a 25% increase in serum IgM from the lowest attained response value or progression of clinically significant disease related symptoms. |
| Time to Next Therapy With Single Agent RAD001 Therapy in Previously Untreated WM | End of follow-up, an average of 18 months | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| RAD001 RAD001, oral, 10 mg, daily
RAD001 : Taken orally once a day | 33 |
| Total | 33 |
Baseline characteristics
| Characteristic | RAD001 |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 12 Participants |
| Age, Categorical Between 18 and 65 years | 21 Participants |
| Region of Enrollment United States | 33 participants |
| Sex: Female, Male Female | 9 Participants |
| Sex: Female, Male Male | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 33 / 33 |
| serious Total, serious adverse events | 7 / 33 |
Outcome results
Primary
Overall Response Rate of RAD001 in Patients With Previously Untreated WM
Overall Response = Complete Response + Near Complete Response + Very Good Partial Response + Partial Response + Minor Response Complete Response: resolution of all symptoms, normalization of serum IgM levels with complete disappearance of IgM paraprotein by immunofixation, and resolution of any adenopathy or splenomegaly. A near CR (nCR) is defined as fulfilling all CR criteria in the presence of positive immunofixation test for an IgM paraprotein. Very Good Partial Response: \> 90% reduction in serum IgM levels. Partial Response: \> 50% reduction in serum IgM levels. Minor Response: 25-49% reduction in serum IgM levels Progressive Disease: greater than 25% increase in serum IgM level occurs from the lowest attained response value or progression of clinically significant disease related symptom(s). Stable Disease: \< 25% change in serum IgM levels, in the absence of new or increasing adenopathy or splenomegaly and/or other progressive signs or symptoms of WM
Time frame: End of Treatment, an average of 16 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| RAD001 | Overall Response Rate of RAD001 in Patients With Previously Untreated WM | 22 participants |
Primary
Time to Next Therapy With Single Agent RAD001 Therapy in Previously Untreated WM
Time frame: End of follow-up, an average of 18 months
Population: 13 participants were censored due to follow-up ending prior to new therapy initiation.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| RAD001 | Time to Next Therapy With Single Agent RAD001 Therapy in Previously Untreated WM | 15 Months |
Primary
Time to Progression With Single Agent RAD001 Therapy in Previously Untreated WM.
Progression is defined as a 25% increase in serum IgM from the lowest attained response value or progression of clinically significant disease related symptoms.
Time frame: End of Treatment, an average of 16 months
Population: 13 participants were excluded from this analysis due to treatment and follow-up ending prior to progression.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| RAD001 | Time to Progression With Single Agent RAD001 Therapy in Previously Untreated WM. | 21 Months |