Everolimus Plus Rituximab for Relapsed/Refractory Diffuse Large B Cell Lymphoma

NCT00869999 | Completed Phase 2 Results DMC

• 1 other identifier: 09-002
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Diffuse Large B-cell Lymphoma

Keywords

rituximab; everolimus; DLBCL; mTOR

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate

  Complete response plus partial response after 6 cycles. Response rate will be evaluated by using the modified Cheson criteria for lymphoma response. Complete response requires all of the following: 1) PET positive prior to therapy: mass of any size permitted if PET negative. Variable FDG-avid or PET negative prior to therapy: regression to normal size on CT (\</= 1.5cm in their greatest transverse diameter for nodes \>/= 1.5 cm before therapy) 2) Spleen (if enlarged before therapy) must have regressed in size and must not be palpable, 3) If bone marrow is known to be involved, repeat biopsy documents clearance. Partial response requires 1) \>/= 50% decrease in SPD, 2) No new sites of disease or increase in the size of other nodes, liver or spleen, 3) Splenic and hepatic nodules must regress by at least 50% in SPD

  Assessed at the conclusion of cycle 2, cycle 4 and cycle 6

Secondary Outcomes (2)

• Duration of Overall Response

  2 years

• Progression-free Survival

  2 years

Interventions

Everolimus DRUG

Taken orally once daily in the morning

rituximab DRUG

Given intravenously on Days 1, 8, 15, and 22 of Cycle 1 then on Day 1 of cycles 2-6

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Beth Israel Deaconess Medical Center: collaborator
• Dana-Farber Cancer Institute: collaborator
• Novartis: collaborator

Study Sites (2)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Beth Israel Deaconsess Medical Center

Boston, Massachusetts, 02215, United States

Location

Related Publications (1)

• Barnes JA, Jacobsen E, Feng Y, Freedman A, Hochberg EP, LaCasce AS, Armand P, Joyce R, Sohani AR, Rodig SJ, Neuberg D, Fisher DC, Abramson JS. Everolimus in combination with rituximab induces complete responses in heavily pretreated diffuse large B-cell lymphoma. Haematologica. 2013 Apr;98(4):615-9. doi: 10.3324/haematol.2012.075184. Epub 2012 Nov 9.

  PMID: 23144193 DERIVED

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Interventions

Everolimus; Rituximab

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Jeffrey Barnes, MD
• Organization: Massachusetts General Hospital Cancer Center

jabarnes@partners.org

617-724-4000

Study Officials

• Jeremy S. Abramson, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Lymphoma Program

Study Record Dates

• First Submitted: March 25, 2009
• First Posted: March 26, 2009
• Study Start: May 1, 2009
• Primary Completion: November 1, 2011
• Study Completion: November 1, 2011
• Last Updated: October 27, 2014
• Results First Posted: October 27, 2014

Record last verified: 2013-10

Locations

US (2)