Everolimus, Bortezomib and/or Rituximab in Patients With Relapsed/Refractory Waldenstrom's Macroglobulinemia

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Novartis
Millennium Pharmaceuticals, Inc.
Information provided by (Responsible Party):
Irene Ghobrial, MD, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:
NCT01125293
First received: March 16, 2010
Last updated: October 2, 2014
Last verified: October 2014
  Purpose

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 Intervention Phase
Waldenstrom's Macroglobulinemia
Drug: Everolimus
Drug: Rituximab
Drug: Bortezomib
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Dana-Farber Cancer Institute:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
    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:
  • To assess the safety of the combination of everolimus/rituximab or everolimus/bortezomib/rituximab in the Phase II study. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: No ]
  • To identify molecular regulators of response/resistance using tumor samples pre and post-treatment. [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 70
Study Start Date: March 2010
Estimated Study Completion Date: October 2015
Estimated Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01125293

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

No publications provided

Responsible Party: Irene Ghobrial, MD, Principal Investigator, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT01125293     History of Changes
Other Study ID Numbers: 09-280, R01FD003743; X05310
Study First Received: March 16, 2010
Last Updated: October 2, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Dana-Farber Cancer Institute:
everolimus
rituximab
bortezomib
RAD001
Rituxan
Velcade

Additional relevant MeSH terms:
Waldenstrom Macroglobulinemia
Blood Protein Disorders
Cardiovascular Diseases
Hematologic Diseases
Hemorrhagic Disorders
Hemostatic Disorders
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Plasma Cell
Paraproteinemias
Vascular Diseases
Bortezomib
Everolimus
Rituximab
Sirolimus
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Antineoplastic Agents
Antirheumatic Agents
Immunologic Factors
Immunosuppressive Agents
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 21, 2014