Maintenance Rituximab With mTor Inhibition After High-dose Consolidative Therapy in Lymphoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2015 by Sidney Kimmel Comprehensive Cancer Center
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center Identifier:
First received: July 27, 2012
Last updated: October 30, 2015
Last verified: October 2015
This research is being done to determine if combining an investigational drug called Everolimus with Rituximab can reduce the risk of your cancer from returning after high dose chemotherapy.

Condition Intervention Phase
CD20+, B-cell Lymphomas
Mantle Cell Lymphoma
Non-Mantle Cell Low Grade B Cell Lymphomas (SLL/CLL)
Transformed Lymphoma/DLBCL/PMBCL
Hodgkin's Disease
Gray Zone Lymphoma
Drug: Everolimus and 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: A Trial of Maintenance Rituximab With mTor Inhibition After High-dose Consolidative Therapy in CD20+, B-cell Lymphomas, Gray Zone Lymphoma, and Hodgkin's Lymphoma

Resource links provided by NLM:

Further study details as provided by Sidney Kimmel Comprehensive Cancer Center:

Primary Outcome Measures:
  • Number of patients with adverse events when given treatment with maintenance rituximab and prolonged mTOR inhibition with everolimus in CD20+, B cell lymphomas, Gray Zone Lymphoma, and Hodgkin's Lymphoma after high-dose consolidative therapy [ Designated as safety issue: Yes ]
    • Avoidance of ≥ grade III common toxicities (CTCAE version 4.0)

Secondary Outcome Measures:
  • 1) Event free survival at three years based on histology [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
    • EFS will be histology grade specific: Mantle cell lymphoma group, low-grade lymphoma group, high-grade lymphoma group

  • 2) Reduction of the frequency of circulating cancer cells due to maintenance rituximab with everolimus treatment [ Designated as safety issue: No ]
  • 3) Sensitivity, in-vivo, of relapsed disease to mTor kinase inhibition. [ Designated as safety issue: No ]

Estimated Enrollment: 60
Study Start Date: August 2012
Estimated Study Completion Date: July 2018
Estimated Primary Completion Date: July 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Everolimus and Rituximab
After your body has fully recovered from the effects of the chemotherapy, you will receive everolimus daily for one year and IV rituximab four times during that year.
Drug: Everolimus and Rituximab
Everolimus: The initial dose of everolimus will be 5mg orally daily for a total of one year to maintain a target trough concentration between 3-15 ng/mL Rituximab: 375mg/m2 day +1 and then every 90 days for 1 year (a total of 4 infusions)
Other Name: RAD001

Detailed Description:

Everolimus is a pill that interferes with lymphoma cell growth by blocking a cellular pathway important in causing cancer cells to grow, called mTor. Rituximab is an intravenous medication that specifically attacks a protein commonly found on lymphoma cells called CD20.

Rituximab is already widely used to treat multiple forms of lymphoma. Moreover, continuing rituximab after the completion of chemotherapy is already commonly used to help patients stay in remission longer. Everolimus has been shown in many types of relapsed lymphoma to decrease the size of lymph nodes by itself. Everolimus is approved by the Food and Drug Administration (FDA) for the treatment of advanced kidney cancer and subependymal giant cell astocytoma. It is not approved for use in lymphoma. The use of everolimus in this research study is investigational. The word "investigational" means that everolimus is not approved for marketing by the Food and Drug Administration (FDA). The FDA is allowing the use of everolimus in this study.

The combination of everolimus and rituximab for 1 year after high dose therapy is also new. We believe the combination of these medications right after your chemotherapy will be more effective in attacking your remaining cancer before they have time to re-grow.

The usual treatment of lymphoma after high-dose chemotherapy is observation. After your body has fully recovered from the effects of the chemotherapy, you will receive everolimus daily for one year and IV rituximab four times during that year.


Ages Eligible for Study:   18 Years to 100 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Age >18 years of age
  • ECOG performance status ≤ 2
  • INR ≤ 2
  • Adequate renal and hepatic function defined as a serum creatinine <2.0mg/dL, total bilirubin <5mg/dL, and AST and ALT ˂ 2.5 ULN.
  • Platelet count >75 x 109/L
  • Hemoglobin >10mg/dL
  • ANC >3.0x109/L
  • Fasting serum cholesterol ≤300 mg/dL OR ≤7.75 mmol/L and fasting triglycerides ≤ 2.5 x ULN. NOTE: In case one or both of these thresholds are exceeded, the patient can only be included after initiation of appropriate lipid lowering medication.
  • A willingness to use an accepted and effective method of birth control for sexually active women of childbearing potential during the study and for 8 weeks after the end of study drug treatment.
  • Ability to sign informed consent

Exclusion Criteria:

Patient who have previously received an mTor inhibitor

  • Patients who are pre-terminal or moribund
  • Patients currently receiving anticancer therapies or who have received anticancer therapies within 4 weeks of the start of Everolimus (including chemotherapy, radiation therapy, antibody based therapy, etc.)
  • Uncontrolled diabetes mellitus as defined by HbA1c>8% despite adequate therapy. Patients with a known history of impaired fasting glucose or diabetes mellitus (DM) may be included, however blood glucose and antidiabetic treatment must be monitored closely throughout the trial and adjusted as necessary
  • Chronic treatment with corticosteroids or other immunosuppressive agents. Topical or inhaled cortosteroids are allowed
  • Patients who have received live attenuated vaccines within 1 week of start of Everolimus and during the study. Patient should also avoid close contact with others who have received live attenuated vaccines. Examples of live attenuated vaccines include intranasal influenza, measles, mumps, rubella, oral polio, BCG, yellow fever, varicella and TY21a typhoid vaccines;
  • Patients who have a history of another primary solild malignancy, with the exceptions of: non-melanoma skin cancer, and carcinoma in situ of the cervix, uteri, or breast from which the patient has been disease free for ≥3 years;
  • Patients with a history of non-compliance to medical regimens or who are considered potentially unreliable or will not be able to complete the entire study;
  • Patients with active bacterial or fungal infections requiring oral or intravenous antimicrobials are not eligible until resolution of the infection
  • Female patients who are pregnant or breast feeding, or of reproductive potential whoe are not using effective birth control methods. Adequate contraception must be used throughout the trial and for 8 weeks after the last dose of study drug.
  • Male patients whose sexual partner(s) are WOCBP who are not willing to use adequate contraception, during the study and for 8 weeks after the end of treatment
  • Patients with known intolerance to rituximab
  • Known history of HIV or Hepatitis C
  • Active Hepatitis B as defined by seropositivity for hepatitis B surface antigen. Subjects with positive hepatitis B core antibody titers and normal liver transaminases are allowed provided that prophylaxis is administered per institutional guidelines. Please see Addendum 8 for the action to be taken for patients with positive baseline hepatitis B results.
  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 identifier: NCT01665768

Contact: Douglas Gladstone, MD 410-955-8781

United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Recruiting
Baltimore, Maryland, United States, 21231
Contact: Clinical Trials Office- SKCCC    410-955-8804   
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center
Principal Investigator: Douglas Gladstone, MD Sidney Kimmel Comprehensive Cancer Center
  More Information

No publications provided

Responsible Party: Sidney Kimmel Comprehensive Cancer Center Identifier: NCT01665768     History of Changes
Other Study ID Numbers: J1228, NA_00067315
Study First Received: July 27, 2012
Last Updated: October 30, 2015
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Hodgkin Disease
Lymphoma, B-Cell
Lymphoma, Mantle-Cell
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoma, Non-Hodgkin
Lymphoproliferative Disorders
Neoplasms by Histologic Type
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 processed this record on November 30, 2015