Clinical Trials /

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

NCT01665768

Description:

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.

Related Conditions:
  • Hodgkin Lymphoma
  • Mature B-Cell Non-Hodgkin Lymphoma
Recruiting Status:

Completed

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Maintenance Rituximab With mTor Inhibition After High-dose Consolidative Therapy in Lymphoma
  • 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

Clinical Trial IDs

  • ORG STUDY ID: J1228
  • SECONDARY ID: NA_00067315
  • NCT ID: NCT01665768

Conditions

  • 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

Interventions

DrugSynonymsArms
EverolimusRAD001Everolimus and Rituximab
RituximabRituxanEverolimus and Rituximab

Purpose

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.

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.
    

Trial Arms

NameTypeDescriptionInterventions
Everolimus and RituximabExperimentalEverolimus daily for one year and IV rituximab four times during that year.
  • Everolimus
  • Rituximab

Eligibility Criteria

        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.
      
Maximum Eligible Age:100 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Safety as Assessed by Avoidance of Grade 3-4 Adverse Events
Time Frame:Up to 3 years
Safety Issue:
Description:Number of participants who did not experience at least one grade 3-4 adverse event by CTCAE 4.0.

Secondary Outcome Measures

Measure:Event Free Survival (EFS)
Time Frame:2.5 years
Safety Issue:
Description:Percentage of participants alive without disease progression. As defined by Cheson criteria, disease progression is a new lesion or >= 50% increase in the size of previously identified sites of disease. EFS was estimated using Kaplan-Meier survival analysis.
Measure:Percentage Change in the Frequency of Circulating Cancer Cells
Time Frame:Baseline, 1 year, 2 years and 3 years
Safety Issue:
Description:Percentage change in circulating cancer cells between baseline and each timepoint noted below.
Measure:Percentage Change in Cancer Cells When mTOR Kinase Inhibition is Applied
Time Frame:1 year, 2 years, and 3 years
Safety Issue:
Description:Percentage change in cancer cells when mTOR inhibition is applied in the laboratory. Samples from participants will be evaluated at each timepoint noted below.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Completed
Lead Sponsor:Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Last Updated

September 28, 2020