Thalidomide and Rituximab in Waldenstrom's Macroglobulinemia

This study has been completed.
Sponsor:
Collaborators:
Dana-Farber Cancer Institute
Massachusetts General Hospital
Beth Israel Deaconess Medical Center
Brigham and Women's Hospital
Cape Cod Healthcare
Information provided by (Responsible Party):
Steven P. Treon, MD, PhD, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:
NCT00142116
First received: September 1, 2005
Last updated: May 8, 2014
Last verified: May 2014
  Purpose

The purpose of this study is to determine the percentage of people who can attain remission and the length of time such responses to therapy are sustained, as well as the side effects that might result from rituximab and thalidomide in people with lymphoplasmacytic lymphoma.


Condition Intervention Phase
Waldenstrom's Macroglobulinemia
Lymphoplasmacytic Lymphoma
Drug: Thalidomide
Drug: Rituximab
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 II Study of Thalidomide and Rituximab in Waldenstrom's Macroglobulinemia

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Objective Response Rate [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    Response determinations were made using modified consensus panel criteria from the Third International Workshop on WM, and response rates were determined on an evaluable basis. A complete response was defined as having resolution of all symptoms, normalization of serum IgM levels with complete disappearance of IgM paraprotein by immunofixation, and resolution of any adenopathy or splenomegaly. Patients achieving a partial response and a minor response were defined as achieving a more than or equal to 50% and more than or equal to 25% reduction in serum IgM levels, respectively. Patients with stable disease were defined as having less than 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. Progressive disease was defined as a greater than 25% increase in serum IgM level occurred from the lowest attained response value or progression of clinically significant disease-related symptom(s).

  • Time to Progression [ Time Frame: 49.1 months ] [ Designated as safety issue: No ]
    Time to disease progression (TTP) was calculated from the start of therapy using the Kaplan-Meier method.


Secondary Outcome Measures:
  • To Identify the Mechanism(s) of Action for Combined Thalidomide and Rituximab Activity. [ Time Frame: 3 years ] [ Designated as safety issue: No ]

Enrollment: 25
Study Start Date: May 2003
Study Completion Date: February 2008
Primary Completion Date: February 2004 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Thalidomide and Rituximab

Thalidomide 200mg orally once a day for 14 weeks if that dosage is tolerated well, it will be increased to 400mg for up to 50 weeks

Rituximab Given intravenously once weekly for 4 weeks beginning the second week of study treatment. If tolerated well, this may be repeated 8 weeks later.

Drug: Thalidomide
200mg orally once a day for 14 weeks if that dosage is tolerated well, it will be increased to 400mg for up to 50 weeks.
Other Name: Thalomid
Drug: Rituximab
Given intravenously once weekly for 4 weeks beginning the second week of study treatment. If tolerated well, this may be repeated 8 weeks later.
Other Name: Rituxan

Detailed Description:
  • Patients will receive thalidomide(200mg) orally once daily for two weeks. If after two weeks of thalidomide, the patient is doing well the dose of thalidomide will increase (400mg) and they will remain on it for up to 50 additional weeks. The length of time a patient is on thalidomide will depend upon how they are responding to therapy.
  • During the second week of the study patients will also begin receiving rituximab intravenously once weekly for 4 weeks, which may then be repeated 8 weeks later depending upon the response.
  • A determination of how the patient is responding will be made based on testing conducted at 12 weeks. This testing includes blood tests and possibly a bone marrow biopsy. If it is determined that the disease is not progressing, patients will begin a second phase of treatment which includes 4 additional weekly infusions of rituximab and the continuation of oral thalidomide.
  • If it is determined at the 12-week evaluation, or at any time thereafter, that the disease has progressed (by studying serum immunoglobulin M (IgM) levels, bone marrow involvement, tumor cells, and/or development of new signs and symptoms) then the patient will be removed from the study.
  • Periodic examinations and tests will be done to determine how the patient is doing, what response and side effects (if any) the patient may be having from the study drugs. If patient is responding to therapy then they will remain on this study and followed for a period of two years.
  • Bone marrow biopsies and aspirations will be obtained at 3-6 month intervals extending for 2 years following the last treatment.
  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Clinicopathological diagnosis of Waldenstrom's macroglobulinemia requiring therapy
  • Baseline staging requirements
  • Absolute Neutrophil Count > 500/microliter (uL)
  • Platelet Count > 25,000/uL
  • Serum creatinine < 2.5mg/dL
  • Total bilirubin and transaminase (SGOT) < 2.5 X Upper Limit of Normal (ULN)
  • Greater than 18 years of age
  • Life expectancy of 3 months or greater
  • Eastern Cooperative Oncology Group (ECOG) status performance of 0-2

Exclusion Criteria:

  • Chemotherapy, steroid therapy, or radiation therapy within 30 days of study entry
  • Pregnant or lactating women
  • Serious co-morbid disease
  • Uncontrolled bacterial, fungal or viral infection
  • Active second malignancy
  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: NCT00142116

Locations
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
Sponsors and Collaborators
Steven P. Treon, MD, PhD
Dana-Farber Cancer Institute
Massachusetts General Hospital
Beth Israel Deaconess Medical Center
Brigham and Women's Hospital
Cape Cod Healthcare
Investigators
Principal Investigator: Steven P. Treon, MD, MA, PhD Dana-Farber Cancer Institute
  More Information

Publications:
Responsible Party: Steven P. Treon, MD, PhD, Director, Bing Center for WM, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT00142116     History of Changes
Other Study ID Numbers: 03-077
Study First Received: September 1, 2005
Results First Received: June 13, 2013
Last Updated: May 8, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Dana-Farber Cancer Institute:
thalidomide
rituximab
Waldenstrom's

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

ClinicalTrials.gov processed this record on September 30, 2014