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

NCT01334502 | Completed Phase 1

• 3 other identifiers: NCCTG-N1085CDR0000698584NCI-2011-02643
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

RATIONALE: Everolimus may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as rituximab, can block cancer cells in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Drugs used in chemotherapy, such as cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone, work in different ways to stop the growth of cancer cells, either by killing the cells or stopping them from dividing. Giving everolimus together with rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone may kill more cancer cells. PURPOSE: This phase I trial is studying the side effects and the best dose of everolimus when given together with rituximab and combination chemotherapy in treating patients with newly diagnosed untreated diffuse large B-cell lymphoma.

Conditions

Lymphoma

Keywords

contiguous stage II adult diffuse large cell lymphoma; noncontiguous stage II adult diffuse large cell lymphoma; stage III adult diffuse large cell lymphoma; stage IV adult diffuse large cell lymphoma

Outcome Measures

Primary Outcomes (4)

• MTD of everolimus in combination with R-CHOP

  Up to 15 months post registration to Phase I portion of the study

• Adverse events profile

  Up to 15 months post registration to Phase I portion of the study

• Toxicity profile

  Up to 15 months post registration to Phase I portion of the study

• Proportion of patients who have a significant toxicity

  Up to 2.5 years post registration to Feasibility portion of the study

Secondary Outcomes (2)

• Rate of EFS

  Up to 5 years post treatment of the feasibility portion of the study

• Overall response rate, CR rate, overall survival, PFS, and duration of response

  Up to 5 years post treatment of the feasibility portion of the study

Study Arms (1)

everolimus and RCHOP

EXPERIMENTAL

Patients registered to the study will receive an assigned dose of everolimus by mouth and RCHOP for a maximum of six cycles. Each cycle is a total of 21 days. RCHOP consists of 375 mg/m2 IV rituximab, 750 mg/m2 IV cyclophosphamide, 50 mg/m2 IV doxorubicin, 1.4 mg/m2 IV vincristine and 100 mg/m2 by mouth QD prednisone. The study includes a Phase I component to determine the maximum tolerated dose of everolimus and the second component determines the feasibility of therapy administered to lymphoma patients.

Biological: rituximab; Drug: cyclophosphamide; Drug: doxorubicin hydrochloride; Drug: everolimus; Drug: prednisone; Drug: vincristine sulfate

Interventions

rituximab BIOLOGICAL

PO

everolimus and RCHOP

cyclophosphamide DRUG

IV

everolimus and RCHOP

doxorubicin hydrochloride DRUG

IV

everolimus and RCHOP

everolimus DRUG

PO

everolimus and RCHOP

prednisone DRUG

PO

everolimus and RCHOP

vincristine sulfate DRUG

IV

everolimus and RCHOP

Eligibility Criteria

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

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)

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Alliance for Clinical Trials in Oncology: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Mayo Clinic Cancer Center

Rochester, Minnesota, 55905, United States

Location

Related Publications (1)

• Johnston PB, LaPlant B, McPhail E, Habermann TM, Inwards DJ, Micallef IN, Colgan JP, Nowakowski GS, Ansell SM, Witzig TE. Everolimus combined with R-CHOP-21 for new, untreated, diffuse large B-cell lymphoma (NCCTG 1085 [Alliance]): safety and efficacy results of a phase 1 and feasibility trial. Lancet Haematol. 2016 Jul;3(7):e309-16. doi: 10.1016/S2352-3026(16)30040-0. Epub 2016 Jun 5.

  PMID: 27374464 DERIVED

MeSH Terms

Conditions

Lymphoma; Lymphoma, Large B-Cell, Diffuse

Interventions

Rituximab; Cyclophosphamide; Doxorubicin; Everolimus; Prednisone; Vincristine

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Sirolimus; Macrolides; Lactones; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines

Study Officials

• Patrick Johnston, MD, PhD

  Mayo Clinic

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 12, 2011
• First Posted: April 13, 2011
• Study Start: March 1, 2012
• Primary Completion: February 1, 2015
• Study Completion: August 1, 2017
• Last Updated: August 10, 2017

Record last verified: 2017-08

Locations

US (1)