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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00976248
Recruitment Status : Completed
First Posted : September 14, 2009
Results First Posted : June 16, 2014
Last Update Posted : October 3, 2018
Brigham and Women's Hospital
Information provided by (Responsible Party):
Steven P. Treon, MD, PhD, Dana-Farber Cancer Institute

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.

Condition or disease Intervention/treatment Phase
Waldenstrom's Macroglobulinemia Drug: RAD001 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 33 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Study of Everolimus (RAD001) in Primary Therapy of Waldenstrom's Macroglobulinemia
Study Start Date : November 2009
Actual Primary Completion Date : July 2016
Actual Study Completion Date : July 2018

Arm Intervention/treatment
Experimental: RAD001
RAD001, oral, 10 mg, daily
Drug: RAD001
Taken orally once a day
Other Name: Everolimus

Primary Outcome Measures :
  1. Overall Response Rate of RAD001 in Patients With Previously Untreated WM [ Time Frame: 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

  2. Time to Progression With Single Agent RAD001 Therapy in Previously Untreated WM. [ Time Frame: 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.

  3. Time to Next Therapy With Single Agent RAD001 Therapy in Previously Untreated WM [ Time Frame: End of follow-up, an average of 18 months ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00976248

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United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
Sponsors and Collaborators
Dana-Farber Cancer Institute
Brigham and Women's Hospital
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Principal Investigator: Steven Treon, MD Dana-Farber Cancer Institute
Publications of Results:
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
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.

Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Steven P. Treon, MD, PhD, Director, Bing Center, Dana-Farber Cancer Institute Identifier: NCT00976248    
Other Study ID Numbers: 09-214
First Posted: September 14, 2009    Key Record Dates
Results First Posted: June 16, 2014
Last Update Posted: October 3, 2018
Last Verified: September 2018
Keywords provided by Steven P. Treon, MD, PhD, Dana-Farber Cancer Institute:
Additional relevant MeSH terms:
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Waldenstrom Macroglobulinemia
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs