Everolimus, Bortezomib and/or Rituximab in Patients With Relapsed/Refractory 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: NCT01125293
Recruitment Status : Active, not recruiting
First Posted : May 18, 2010
Last Update Posted : November 5, 2018
Millennium Pharmaceuticals, Inc.
Information provided by (Responsible Party):
Irene Ghobrial, MD, Dana-Farber Cancer Institute

Brief Summary:

The purpose of this research study is to test the safety of the combination of everolimus, rituximab and bortezomib. Everolimus is a drug that works by preventing cells in your body from growing and dividing. Information from basic and other clinical research suggests that everolimus may also inhibit tumor growth in people with relapsed or refractory lymphoma. The FDA has approved everolimus for the treatment of multiple myeloma, a cancer that is closely related to Waldenstrom's Macroglobulinemia. Rituximab is approved by the FDA for the treatment of non-Hodgkin's lymphoma, which included Waldenstrom's Macroglobulinemia.

Funding Source - FDA OOPD

Condition or disease Intervention/treatment Phase
Waldenstrom's Macroglobulinemia Drug: Everolimus Drug: Rituximab Drug: Bortezomib Phase 1 Phase 2

Detailed Description:
  • Since we are looking for the highest dose of a combination of study drugs that can be administered safely without severe or unmanageable side effects in participants that have Waldenstrom's Macroglobulinemia, not everyone who participates in this research study will receive the same combination of study drugs or the same dose of the study drug.
  • In this research study every 4 week (28 day) period is called a cycle. While on study, participants will receive up to 6 cycles of combination treatment followed by everolimus alone for up to 2 years.
  • Participants will take everolimus by mouth everyday, and will receive rituximab intravenously on days 1, 8, 15 and 22 on Cycle 1 and Cycle 4 only. If the participant receives bortezomib, it will be given intravenously on days 1, 8 and 15 of every cycle.
  • After the third cycle, tests will be done to see how the disease is responding to the study treatment. If the disease stays the same, or is helped, the participant will continue to get the combination of study treatment for another 3 cycles.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 46 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I/II Study of Combination Everolimus (RAD001), and Rituximab (Rituxan), OR Everolimus, Bortezomib (Velcade, PS-341), and Rituximab in Patients With Relapsed and/or Relapsed/Refractory Waldenstrom's Macroglobulinemia
Study Start Date : March 2010
Estimated Primary Completion Date : February 2020
Estimated Study Completion Date : February 2020

Arm Intervention/treatment
Experimental: single arm
Combination of everolimus & rituximab with bortezomib in patients with relapsed or refractory WM
Drug: Everolimus
Taken orally on a daily basis
Other Name: RAD001

Drug: Rituximab
Given intravenously on days 1, 8, 15 and 22 of Cycle 1 and Cycle 4 only
Other Name: Rituxan

Drug: Bortezomib
Given intravenously on days 1, 8 and 15 of every cycle
Other Names:
  • Velcade
  • PS-341

Primary Outcome Measures :
  1. Phase I/II Study of Combination Everolimus (RAD001), and Rituximab (Rituxan), OR Everolimus, Bortezomib (Velcade, PS-341), and Rituximab in Patients with Relapsed and/or Relapsed/Refractory Waldenstrom's Macroglobulinemia [ Time Frame: 2 years ]
    To determine the safety and maximum tolerated dose (MTD) of the combination of everolimus/rituximab or everolimus/bortezomib/rituximab and to assess the depth of response to the combination of everolimus/bortezomib/rituximab.

Secondary Outcome Measures :
  1. To assess the safety of the combination of everolimus/rituximab or everolimus/bortezomib/rituximab in the Phase II study. [ Time Frame: 2 years ]
  2. To assess overall response rate, duration of response, time to progression, and progression free survival in these patients in the Phase II study. [ Time Frame: 3 years ]
  3. To identify molecular regulators of response/resistance using tumor samples pre and post-treatment. [ Time Frame: 2 years ]

Information from the National Library of Medicine

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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
  • Patients must have received prior therapies for their WM and have relapsed or refractory WM requiring therapy. Any number of prior therapies is acceptable. Patients must not have been refractory to rituximab. The last rituximab must be at least 3 months prior to the start of treatment. Prior treatment with bortezomib and/or everolimus is permitted.
  • Measurable monoclonal IgM protein in the serum OR measurable quantitative immunoglobulin M (serum IgM).
  • Lymphoplasmacytic cells in the bone marrow during any previous bone marrow biopsy.
  • CD20 positive disease based on any previous bone marrow immuno-histochemistry or flow cytometric analysis performed prior to enrollment.
  • ECOG Performance Status 0, 1 or 2
  • Laboratory values as outlined in the protocol
  • Capable of swallowing intact study medication tablets
  • Life expectancy of 12 weeks or greater

Exclusion Criteria:

  • Uncontrolled infection
  • Other active malignancies
  • Cytotoxic chemotherapy 3 weeks or less, or biologic or targeted novel therapy 2 weeks or less, or corticosteroids 2 weeks or less, or radiation therapy 2 weeks or less, or any ancillary treatment considered investigation 2 weeks or less, prior to registration. Patients may be receiving chronic corticosteroids if they are being given for disorders other than WM.
  • Pregnant women, nursing women, men or women of childbearing potential who are unwilling to employ adequate contraception throughout the trial and for 8 weeks after the last dose of study treatment.
  • Known to be HIV positive, or Hepatitis B positive. If the status of HIV is not known and patients are not at risk, then patients will not be specifically tested for HIV. Patients will be tested for Hepatitis B at time of screening. If patients are not considered high risk and have been vaccinated at an earlier date, results of the test are not required at the time of registration. For patients that are high risk, results must be obtained prior to registration.
  • Patient has Grade 2 or higher peripheral neuropathy within 14 days of enrollment
  • Diagnosed or treated for another malignancy within 3 years of enrollment, with the exception of complete resection fo basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy.
  • Severely impaired lung function
  • Uncontrolled diabetes
  • Liver disease such as cirrhosis, chronic active hepatitis or chronic persistent hepatitis
  • Impairment of gastrointestinal function or gastrointestinal disease
  • Patients with active, bleeding diathesis
  • Myocardial infarction within 6 months prior to enrollment or had NYHA Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities.
  • Hypersensitivity to everolimus or other rapamycins or to is excipients
  • Patients who may need or are receiving live vaccines for immunization
  • Serious medical or psychiatric illness likely to interfere with participation in this clinical study

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): NCT01125293

United States, Colorado
Colorado Blood Cancer Institute
Denver, Colorado, United States, 80218
United States, Massachusetts
Milford Hospital
Boston, Massachusetts, United States, 01757
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
Sponsors and Collaborators
Dana-Farber Cancer Institute
Millennium Pharmaceuticals, Inc.
Principal Investigator: Irene Ghobrial, MD Dana-Farber Cancer Institute

Responsible Party: Irene Ghobrial, MD, Principal Investigator, Dana-Farber Cancer Institute Identifier: NCT01125293     History of Changes
Other Study ID Numbers: 09-280
R01FD003743; X05310 ( Other Grant/Funding Number: FDAOOPD; Millennium )
R01FD003743 ( U.S. NIH Grant/Contract )
First Posted: May 18, 2010    Key Record Dates
Last Update Posted: November 5, 2018
Last Verified: November 2018

Keywords provided by Irene Ghobrial, MD, Dana-Farber Cancer Institute:

Additional relevant MeSH terms:
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
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Immunosuppressive Agents
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents