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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

Phase 1/Phase 2
18 Years
Open (Enrolling)
Waldenstrom's Macroglobulinemia

Thank you

Trial Information

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

- 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

- 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.

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

- 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

- 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

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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

Outcome Description:

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.

Outcome Time Frame:

2 years

Safety Issue:


Principal Investigator

Irene Ghobrial, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Dana-Farber Cancer Institute


United States: Food and Drug Administration

Study ID:




Start Date:

March 2010

Completion Date:

October 2014

Related Keywords:

  • Waldenstrom's Macroglobulinemia
  • everolimus
  • rituximab
  • bortezomib
  • RAD001
  • Rituxan
  • Velcade
  • Waldenstrom Macroglobulinemia



Dana-Farber Cancer InstituteBoston, Massachusetts  02115
Colorado Blood Cancer InstituteDenver, Colorado  80218
Milford HospitalMilford, Massachusetts  01757