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Everolimus Plus Rituximab for Relapsed/Refractory Diffuse Large B Cell Lymphoma
This study is currently recruiting participants.
Verified by Massachusetts General Hospital, May 2009
First Received: March 25, 2009   Last Updated: May 6, 2009   History of Changes
Sponsors and Collaborators: Massachusetts General Hospital
Beth Israel Deaconess Medical Center
Novartis
Information provided by: Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT00869999
  Purpose

Everolimus is an oral mTOR inhibitor with demonstrated preliminary efficacy and safety in diffuse large B-cell lymphoma (DLBCL) in both preclinical and clinical studies. The purpose of this research study is to determine whether Everolimus plus rituximab is safe and effective in participants with relapsed or refractory DLBCL. Everolimus is an investigational drug that works by blocking a special protein that helps cancer cells grow. The safety and effectiveness of Everolimus in the treatment of DLBCL has not yet been fully determined and is still investigational. The other drug in this study, rituximab, is approved by the US Food and Drug Administration (FDA) for use in patients who have diffuse large B-cell lymphoma and certain other types of non-Hodgkin lymphoma. Rituximab is a drug that destroys both normal and cancerous B-cells.


Condition Intervention Phase
Diffuse Large B-Cell Lymphoma
Drug: Everolimus
Drug: rituximab
Phase II

MedlinePlus related topics: Lymphoma
Drug Information available for: Everolimus Rituximab
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Non-Randomized, Open Label, Single Group Assignment, Safety/Efficacy Study
Official Title: Everolimus in Combination With Rituximab for Relapsed/Refractory Diffuse Large B Cell Lymphoma

Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:
  • Determine clinical efficacy of Everolimus in combination with rituximab in relapsed/refractory DLBCL [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Determine progression-free survival and duration of response [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Assess safety of this combination in relapsed/refractory DLBCL patients [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  • Assess effect of Everolimus on a PBMC biomarker of mTOR inhibition [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Correlate response with pharmacodynamic evidence of mTOR inhibition in PBMCs [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 25
Study Start Date: May 2009
Estimated Primary Completion Date: March 2011 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Everolimus
    Taken orally once daily in the morning
    Drug: rituximab
    Given intravenously on Days 1, 8, 15, and 22 of Cycle 1 then on Day 1 of cycles 2-6
Detailed Description:

Participants will receive oral Everolimus and intravenous rituximab for DLBCL that has relapsed or been refractory to prior therapy.

  • Each treatment cycle lasts 28 days (4 weeks). Everolimus will be taken orally, once daily in the morning.
  • Rituximab will be administered by an intravenous (IV) infusion on Days 1, 8, 15 and 22 of Cycle 1. In Cycles 2-6, rituximab will be administered only on Day 1 of each cycle.
  • Participants will come into the clinic weekly during the first cycle, then on Day 1 of all cycles thereafter. The following tests and procedures will be performed:
  • Weekly During Cycle 1: blood tests
  • Day 1 of all Subsequent Cycles: brief physical examination; review of current medications, treatments, symptoms and side effects; vital signs; performance status evaluation; blood tests.
  • A full body CT and PET scan to assess the participants tumor will be done within 7 days of completing cycles 2, 4, 6, 9 and 12.

Responding subjects may receive up to 6 cycles of Everolimus plus rituximab, and an additional 6 months of oral Everolimus for participants continuing to respond.

  Eligibility

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

Inclusion Criteria:

  • Histologically determined DLBCL that is relapsed or primary refractory after initial therapy
  • Greater than 1 prior line of chemotherapy (including an anthracycline unless contraindicated) or immunotherapy. Patients must have relapsed after autologous stem cell transplantation, not be eligible for autologous stem call transplantation in the judgment of the investigator, or refuse autologous stem cell transplantation. Salvage chemotherapy and high dose conditioning for autologous stem cell transplantation count as two separate regimens.
  • Measurable disease that has not been previously irradiated on PET-CT of at least 2cm, OR if the patient has had previous radiation to the marker lesion(s), there must be evidence of progression since the radiation. Imaging must be completed no greater than 3 weeks from study enrollment.
  • ECOG performance status 0-2
  • 18 years of age or older
  • Life expectancy of greater than 3 months
  • Adequate Organ and marrow function
  • Fasting serum cholesterol of 300 mg/dl or less OR 7.75 mmol/L or less AND fasting triglycerides 2.5 x ULN or less

Exclusion Criteria:

  • Currently receiving anticancer therapies or who have received anticancer therapies within 3 weeks of the start of the study drug
  • Receiving any other investigational agents, or have received investigational agents within 4 weeks of beginning treatment
  • 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 (defined as requiring general anesthesia) or patients that may require major surgery during the course of the study
  • Known leptomeningeal or brain metastases. Imaging or spinal fluid analysis to exclude CNS involvement is not required, unless there is clinical suspicion by the treating investigator
  • Known HIV infection
  • Systemic fungal, bacterial, viral, or other infection not controlled
  • Prior history of malignancy (except for non-melanoma skin cancer or in situ cervical or breast cancer) unless disease free for at least one year.

Patients with prostate cancer are allowed if PSA is less than 1

  • Patients should not receive immunization with attenuated live vaccines within one week of study entry or during study period
  • Severely impaired lung function defined as DLCO of <60%
  • Uncontrolled diabetes as defined by fasting serum glucose > 1.5 x ULN
  • Liver disease such as cirrhosis, chronic active hepatitis or chronic persistent hepatitis
  • Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of Everolimus
  • Active bleeding diathesis
  • Female patients who are pregnant or breastfeeding, or adults of reproductive potential who are not using effective birth control methods
  • Prior treatment with an mTOR inhibitor
  • Known hypersensitivity to murine antibodies,everolimus,other rapamycin
  • Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study
  • No chronic treatment with systemic corticosteroids or other immunosuppressive agents. Topical or inhaled corticosteroids are permitted
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00869999

Contacts
Contact: Jeremy S. Abramson, MD 617-726-8743 jabramson@partners.org

Locations
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Kathleen Shea     617-724-9190     kshea@partners.org    
Contact: Christine Connolly     617-726-5131     cconnolly1@partners.org    
Principal Investigator: Jeremy S. Abramson, MD            
Beth Israel Deaconsess Medical Center Not yet recruiting
Boston, Massachusetts, United States, 02215
Principal Investigator: Robin Joyce, MD            
Sponsors and Collaborators
Massachusetts General Hospital
Beth Israel Deaconess Medical Center
Novartis
Investigators
Principal Investigator: Jeremy S. Abramson, MD Massachusetts General Hospital
  More Information

No publications provided

Responsible Party: Massachusetts General Hospital ( Jeremy S. Abramson, MD )
Study ID Numbers: 09-002
Study First Received: March 25, 2009
Last Updated: May 6, 2009
ClinicalTrials.gov Identifier: NCT00869999     History of Changes
Health Authority: United States: Food and Drug Administration

Keywords provided by Massachusetts General Hospital:
rituximab
everolimus
DLBCL
mTOR

Study placed in the following topic categories:
Everolimus
Lymphoma, Large B-Cell, Diffuse
Immunoproliferative Disorders
Immunologic Factors
Rituximab
Immunosuppressive Agents
Lymphoma, B-Cell
Lymphatic Diseases
B-cell Lymphomas
Lymphoproliferative Disorders
Lymphoma, Non-Hodgkin
Lymphoma, Large-cell
Antirheumatic Agents
Lymphoma

Additional relevant MeSH terms:
Everolimus
Lymphoma, Large B-Cell, Diffuse
Neoplasms by Histologic Type
Immunoproliferative Disorders
Immune System Diseases
Immunologic Factors
Antineoplastic Agents
Rituximab
Physiological Effects of Drugs
Immunosuppressive Agents
Pharmacologic Actions
Lymphoma, B-Cell
Lymphatic Diseases
Neoplasms
Therapeutic Uses
Antirheumatic Agents
Lymphoproliferative Disorders
Lymphoma, Non-Hodgkin
Lymphoma

ClinicalTrials.gov processed this record on May 07, 2009