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

NCT01665768 | Completed Phase 2 Results DMC

• 2 other identifiers: J1228NA_00067315
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 1

Brief Summary

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.

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

Outcome Measures

Primary Outcomes (1)

• Safety as Assessed by Avoidance of Grade 3-4 Adverse Events

  Number of participants who did not experience at least one grade 3-4 adverse event by CTCAE 4.0.

  Up to 3 years

Secondary Outcomes (3)

• Event Free Survival (EFS)

  2.5 years

• Percentage Change in the Frequency of Circulating Cancer Cells

  Baseline, 1 year, 2 years and 3 years

• Percentage Change in Cancer Cells When mTOR Kinase Inhibition is Applied

  1 year, 2 years, and 3 years

Study Arms (1)

Everolimus and Rituximab

EXPERIMENTAL

Everolimus daily for one year and IV rituximab four times during that year.

Drug: Everolimus; Biological: Rituximab

Interventions

Everolimus DRUG

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.

Also known as: RAD001

Everolimus and Rituximab

Rituximab BIOLOGICAL

375mg/m2 day +1 and then every 90 days for 1 year (a total of 4 infusions)

Also known as: Rituxan

Everolimus and Rituximab

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• Novartis Pharmaceuticals: collaborator

Study Sites (1)

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21231, United States

Location

Related Publications (1)

• Schoch LK, Asiama A, Zahurak M, Shanbhag S, Hurtt J, Sawyer K, Swinnen LJ, Wagner-Johnston N, Jones RJ, Ambinder RF, Gladstone DE. Pharmacokinetically-targeted dosed everolimus maintenance therapy in lymphoma patients. Cancer Chemother Pharmacol. 2018 Feb;81(2):347-354. doi: 10.1007/s00280-017-3499-y. Epub 2017 Dec 13.

  PMID: 29234922 RESULT

MeSH Terms

Conditions

Lymphoma, B-Cell; Lymphoma, Mantle-Cell; Hodgkin Disease

Interventions

Everolimus; Rituximab

Condition Hierarchy (Ancestors)

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: Douglas Gladstone, MD
• Organization: Johns Hopkins University

dgladst1@jhmi.edu

4109558781

Study Officials

• Douglas Gladstone, MD

  Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 27, 2012
• First Posted: August 15, 2012
• Study Start: September 1, 2012
• Primary Completion: October 1, 2017
• Study Completion: August 1, 2020
• Last Updated: October 26, 2021
• Results First Posted: December 26, 2018

Record last verified: 2021-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)