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

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2016 by Sidney Kimmel Comprehensive Cancer Center
Sponsor:
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT01665768
First received: July 27, 2012
Last updated: May 17, 2016
Last verified: May 2016

July 27, 2012
May 17, 2016
August 2012
July 2017   (final data collection date for primary outcome measure)
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)
Number of patients with adverse events when given treatment with maintenance rituximab and prolonged mTOR inhibition with everolimus in CD20+, B cell lymphomas and Hodgkin's Lymphoma after high-dose consolidative therapy [ Designated as safety issue: Yes ]
• Avoidance of ≥ grade III common toxicities (CTCAE version 4.0)
Complete list of historical versions of study NCT01665768 on ClinicalTrials.gov Archive Site
  • 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 ]
  • 1) The secondary endpoint of this study is to evaluate 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) To determine whether maintenance rituximab with everolimus treatment reduces the frequency of circulating cancer cells. [ Designated as safety issue: No ]
  • 3) To determine if relapsed disease is sensitive, in-vivo, to mTor kinase inhibition. [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Maintenance Rituximab With mTor Inhibition After High-dose Consolidative Therapy in Lymphoma
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
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.

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.

Interventional
Phase 2
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • 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
Everolimus: The initial dose of everolimus will be 2.5mg 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
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.
Intervention: Drug: Everolimus and Rituximab
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
60
July 2018
July 2017   (final data collection date for primary outcome measure)

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.
Both
18 Years to 100 Years   (Adult, Senior)
No
Contact: Douglas Gladstone, MD 410-955-8781 dgladst1@jhmi.edu
United States
 
NCT01665768
J1228, NA_00067315
Yes
Not Provided
Not Provided
Sidney Kimmel Comprehensive Cancer Center
Sidney Kimmel Comprehensive Cancer Center
Not Provided
Principal Investigator: Douglas Gladstone, MD Sidney Kimmel Comprehensive Cancer Center
Sidney Kimmel Comprehensive Cancer Center
May 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP