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Everolimus (RAD001) in Primary Therapy of Waldenstrom's Macroglobulinemia

Primary Purpose

Waldenstrom's Macroglobulinemia

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
RAD001
Sponsored by
Dana-Farber Cancer Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Waldenstrom's Macroglobulinemia focused on measuring everolimus, RAD001, WM

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Dana-Farber Cancer Institute

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

RAD001

Arm Description

RAD001, oral, 10 mg, daily

Outcomes

Primary Outcome Measures

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 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 to Next Therapy With Single Agent RAD001 Therapy in Previously Untreated WM

Secondary Outcome Measures

Full Information

First Posted
September 11, 2009
Last Updated
September 6, 2018
Sponsor
Dana-Farber Cancer Institute
Collaborators
Brigham and Women's Hospital, Novartis
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1. Study Identification

Unique Protocol Identification Number
NCT00976248
Brief Title
Everolimus (RAD001) in Primary Therapy of Waldenstrom's Macroglobulinemia
Official Title
Phase II Study of Everolimus (RAD001) in Primary Therapy of Waldenstrom's Macroglobulinemia
Study Type
Interventional

2. Study Status

Record Verification Date
September 2018
Overall Recruitment Status
Completed
Study Start Date
November 2009 (undefined)
Primary Completion Date
July 2016 (Actual)
Study Completion Date
July 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Dana-Farber Cancer Institute
Collaborators
Brigham and Women's Hospital, Novartis

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Waldenstrom's Macroglobulinemia
Keywords
everolimus, RAD001, WM

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
33 (Actual)

8. Arms, Groups, and Interventions

Arm Title
RAD001
Arm Type
Experimental
Arm Description
RAD001, oral, 10 mg, daily
Intervention Type
Drug
Intervention Name(s)
RAD001
Other Intervention Name(s)
Everolimus
Intervention Description
Taken orally once a day
Primary Outcome Measure Information:
Title
Overall Response Rate of RAD001 in Patients With Previously Untreated WM
Description
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
Title
Time to Progression With Single Agent RAD001 Therapy in Previously Untreated WM.
Description
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
Title
Time to Next Therapy With Single Agent RAD001 Therapy in Previously Untreated WM
Time Frame
End of follow-up, an average of 18 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Steven Treon, MD
Organizational Affiliation
Dana-Farber Cancer Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Dana-Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States

12. IPD Sharing Statement

Citations:
Citation
Treon SP, Tripsas CK, Ioakimidis L, Warren D, Patterson C, Heffner L, Eradat H, Gregory SA, Thomas S, Advani R, Baz R, Badros, Ashraf Z, Matous J, Anderson KC, Ghobrial IM Prospective, Multicenter Study of the MTOR Inhibitor Everolimus (RAD001) As Primary Therapy in Waldenstrom's Macroglobulinemia ASH Annual Meeting Abstracts 2011 118: 2951
Results Reference
result
Citation
Treon SP, Tripsas CK, Meid K, Patterson CJ, Heffner H, Gregory SA, Thomas SK, Advani RH, Baz R, Badros AZ, Matous J, Murphy TJ, Ghobrial IM. Prospective, Multicenter Study Of The MTOR Inhibitor Everolimus (RAD001) As Primary Therapy In Waldenstrom's Macroglobulinemia Blood 2013 122:1822.
Results Reference
result
PubMed Identifier
27836860
Citation
Treon SP, Meid K, Tripsas C, Heffner LT, Eradat H, Badros AZ, Xu L, Hunter ZR, Yang G, Patterson CJ, Gustine J, Castillo JJ, Matous J, Ghobrial IM. Prospective, Multicenter Clinical Trial of Everolimus as Primary Therapy in Waldenstrom Macroglobulinemia (WMCTG 09-214). Clin Cancer Res. 2017 May 15;23(10):2400-2404. doi: 10.1158/1078-0432.CCR-16-1918. Epub 2016 Nov 11.
Results Reference
derived

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Everolimus (RAD001) in Primary Therapy of Waldenstrom's Macroglobulinemia

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