Everolimus, Rituximab, and Combination Chemotherapy in Treating Patients With Newly Diagnosed Untreated Diffuse Large B-Cell Lymphoma

• Register: ClinicalTrials.gov
• Last refreshed on: 17 October 2012
• Main ID: NCT01334502
• Date of registration: 12/04/2011
• Primary sponsor: North Central Cancer Treatment Group
• Public title: Everolimus, Rituximab, and Combination Chemotherapy in Treating Patients With Newly Diagnosed Untreated Diffuse Large B-Cell Lymphoma
• Scientific title: A Phase I and Feasibility Study of Everolimus (RAD001) Plus R-CHOP for New Untreated Diffuse Large B-Cell Lymphoma (DLBCL)
• Date of first enrolment: March 2012
• Target sample size: 37
• Recruitment status: Recruiting
• URL: http://clinicaltrials.gov/show/NCT01334502
• Study type: Interventional
• Study design: Masking: Open Label, Primary Purpose: Treatment

Countries of recruitment

United States

Contacts

• Name: Clinical Trials Office - All Mayo Clinic Locations

• Name: Patrick Johnston, MD, PhD
• Affiliation: Mayo Clinic

Key inclusion & exclusion criteria

DISEASE CHARACTERISTICS:

- Untreated, histological diagnosis of CD20-positive diffuse large B-cell lymphoma

- Stage II-IV (Ann Arbor Staging)

- Measurable or assessable disease defined as at least one of the following:

- A lymph node or tumor mass that is = 2.0 cm in at least one dimension by CT
portion of PET/CT scan, CT scan, or MRI

- Diffuse infiltration of an organ such as the stomach, bone marrow, peripheral
blood, liver, lungs, or bowel by lymphoma without a discrete mass would
constitute assessable, but not measurable, disease

- Diagnostic tissue slides and paraffin-embedded block must be available

- No CNS lymphoma or cerebrospinal fluid involvement with malignant lymphoma cells

PATIENT CHARACTERISTICS:

- ECOG performance status 0-2

- Absolute neutrophil count (ANC) = 1,500/mm³

- Peripheral platelet count = 100,000/mm³

- Hemoglobin (HgB) > 9.0 g/dL

- Total bilirubin = 1.5 times upper limit of normal (ULN)

- For total bilirubin > 1.5 times ULN, the direct bilirubin must be normal

- Alkaline phosphatase = 3 times ULN (= 5 times ULN if evidence of direct liver
involvement by lymphoma)

- AST = 3 times ULN (= 5 times ULN if evidence of direct liver involvement by lymphoma)

- Creatinine = ULN

- Negative serum or urine pregnancy test

- Not pregnant or nursing

- Men or women of childbearing potential must be willing to employ adequate
contraception throughout the study and for12 months after the last dose of study drug

- Willing to return to the National Central Cancer Treatment Group (NCCTG) enrolling
institution for follow-up

- Willing to provide archival tissue from the primary diagnosis (original lymphoma
lymph node tissue biopsy)

- Willing to abstain from eating grapefruit or drinking grapefruit juice for the
duration of the study

- Diabetic patients who are taking insulin or oral anti-diabetic therapy must have
HbA1c = 8%, or a fasting serum glucose = 110% ULN

- HIV-positive patients must have CD4 count = 400/mm³

- No co-morbid systemic illnesses or other severe concurrent disease that, in the
judgment of the investigator, would make the patient inappropriate for entry into
this study or interfere significantly with the proper assessment of safety and
toxicity of the prescribed regimens

- No immunocompromised patients (other than that related to the use of corticosteroids)
including patients known to be HIV positive with a CD4 count of < 400/mm³

- No uncontrolled intercurrent illness including, but not limited to, any of the
following:

- Ongoing or active infection

- Symptomatic congestive heart failure

- Unstable angina pectoris

- Cardiac arrhythmia

- Severely impaired lung function

- Uncontrolled diabetes as defined by fasting serum glucose > 1.5 times ULN

- Optimal glycemic control should be achieved before starting trial therapy

- Psychiatric illness/social situations that would limit compliance with study
requirements

- Liver disease such as cirrhosis or severe hepatic impairment

- Chronic active hepatitis

- Chronic persistent hepatitis or history of hepatitis B or C

- No other active malignancy except non-melanotic skin cancer or carcinoma in situ of
the cervix

- If there is a history of prior malignancy, patients must not be receiving other
specific treatment (other than hormonal therapy) for their cancer

- No positive hepatitis B antigen (HBsAg) or hepatitis C serology (HCV) tests meeting
the following criteria:

- Hepatitis B surface antigen (HbsAg) and antibody to hepatitis B core (anti-HBc)
or hepatitis C antibody

- All patients must be screened prior to registration

- Patients who have evidence of chronic or acute infection with either hepatitis B
or C may not be treated on this protocol

PRIOR CONCURRENT THERAPY:

- Not receiving any other investigational agent that would be considered as a treatment
for the primary neoplasm

- No planned immunization with attenuated live vaccines = 7 days prior to registration
or during study period

- Close contact with those who have received attenuated live vaccines should be
avoided during treatment with everolimus

- Examples of live vaccines include intranasal influenza, measles, mumps, rubella,
oral polio, BCG, yellow fever, varicella, and TY21a typhoid vaccines

- Not currently on enzyme-inducing anti-convulsants or other strong inducers of CYP3A4
(efavirenz, nevirapine, barbiturates, carbamazepine, modafinil, phenobarbital,
phenytoin, rifabutin, rifampin, pioglitazone, or St. John wort) or strong inhibitors
of CYP3A4 (indinavir, nelfinavir, ritonavir, clarithromycin, itraconazole,
voriconazole, ketoconazole, nefazodone, saquinavir, or telithromycin)



Age minimum: 18 Years
Age maximum: N/A
Gender: Both

Health Condition(s) or Problem(s) studied

Lymphoma

Intervention(s)

Biological: rituximab

Drug: cyclophosphamide

Drug: doxorubicin hydrochloride

Drug: everolimus

Drug: prednisone

Drug: vincristine sulfate

Other: laboratory biomarker analysis

Other: R-CHOP regimen

Primary Outcome(s)

Adverse events profile [Time Frame: Yes]

MTD of everolimus in combination with R-CHOP [Time Frame: No]

Proportion of patients who have a significant toxicity [Time Frame: Yes]

Toxicity profile [Time Frame: Yes]

Secondary Outcome(s)

Overall response rate, CR rate, overall survival, PFS, and duration of response [Time Frame: No]

Rate of EFS at 12 months [Time Frame: No]

Secondary ID(s)

CDR0000698584

NCCTG-N1085

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

National Cancer Institute (NCI)