Everolimus and Lenalidomide in Treating Patients With Relapsed or Refractory Non-Hodgkin or Hodgkin Lymphoma

NCT01075321 | Completed Phase 1 Results DMC

• 5 other identifiers: MC0981NCI-2010-0023509-003801RV-NHL-HL-PI-0466CRAD001NUS113T
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 2

Brief Summary

RATIONALE: Everolimus may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Lenalidomide may stop the growth of cancer cells by blocking blood flow to the cancer. Giving everolimus together with lenalidomide may be an effective treatment for lymphoma. PURPOSE: This phase I/II trial is studying the side effects and best dose of giving everolimus and lenalidomide together and to see how well they work in treating patients with relapsed or refractory non-Hodgkin or Hodgkin lymphoma.

Conditions

Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Peripheral T-cell Lymphoma; Post-transplant Lymphoproliferative Disorder; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Splenic Marginal Zone Lymphoma; Waldenstrom Macroglobulinemia

Outcome Measures

Primary Outcomes (2)

• Number of Patients Reporting Dose-Limiting Toxicity (DLT) (Phase I)

  The number of dose-limiting toxic events (DLT) for this combination of drug treatment will determine the Maximum Tolerated Dose (MTD) in subsequent phases of this study. The following events were defined as a DLT: a grade 4+ Neutropenia or platelet count decrease, a grade 4 infection, or any grade 3+ non-hematologic event as assessed using Common Terminology Criteria for Adverse Events (CTCAE) CTEP Version 4.0. Here, the number of patients reporting a DLT are reported

  After one 28 day cycle

• Best Response to Dose Level 0

  Patients were assessed using the Cheson et al. Revised Response Criteria for Malignant Lymphoma (Cheson, et al 2007). A Complete Response (CR) was defined as the disappearance of all evidence of disease, no palpable nodules and bone marrow cleared on biopsy. A Partial Response (PR) was defined as regression of measureable disease and no new sites, with a 50% decrease in sum of the products of dimension (SPD) of nodal masses, and no increase in spleen or liver size. Patients with Waldenstrom's Macroglobulinemia were eligible to be evaluated as a Minor Response (MR) in which a reduction between 25% and 50% of serum monoclonal IgM was observed. A Progression (PD) was defined as having any new lesions or a 50% increase in the SPD of any previously involved nodes. A Stable Disease (SD) is the absence of any of the previously defined responses.

  Up to 5 years

Secondary Outcomes (4)

• Overall Survival for All Eligible Patients

  Up to 5 years

• Progression-Free Survival For All Eligible Patients

  Up to 5 years

• Duration of Response for All Eligible Patients

  Up to 5 years

• Time to Treatment Failure for All Eligible Patients

  Up to 5 years

Study Arms (1)

Arm I

EXPERIMENTAL

Patients receive oral everolimus once daily and oral lenalidomide once daily on days 1-21. Treatment repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.

Drug: everolimus; Drug: lenalidomide; Other: laboratory biomarker analysis; Genetic: polymorphism analysis; Other: immunohistochemistry staining method; Genetic: microarray analysis; Genetic: fluorescence in situ hybridization

Interventions

everolimus DRUG

Given orally

Also known as: 42-O-(2-hydroxy)ethyl rapamycin, Afinitor, RAD001

Arm I

lenalidomide DRUG

Given orally

Also known as: CC-5013, IMiD-1, Revlimid

Arm I

laboratory biomarker analysis OTHER

Correlative studies

Arm I

polymorphism analysis GENETIC

Correlative studies

Arm I

immunohistochemistry staining method OTHER

Optional correlative studies

Also known as: immunohistochemistry

Arm I

microarray analysis GENETIC

Optional correlative studies

Also known as: gene expression profiling

Arm I

fluorescence in situ hybridization GENETIC

Optional correlative studies

Also known as: fluorescence in situ hybridization (FISH)

Arm I

Eligibility Criteria

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

You may qualify if:

• Histological or cytological confirmation of relapsed or refractory non-Hodgkin lymphoma or Hodgkin lymphoma =\< 6 months prior to registration
• The following disease types are eligible: Study 1 - Aggressive lymphomas- Transformed lymphomas; Diffuse large B cell lymphoma; Mantle cell lymphoma; Follicular lymphoma grade III; Precursor B lymphoblastic leukemia/lymphoma; Mediastinal (thymic) large B-cell lymphoma; Burkitt lymphoma/leukemia; Precursor T lymphoblastic leukemia/lymphoma; Primary cutaneous anaplastic large cell lymphoma; and Anaplastic large cell lymphoma-primary systemic type
• Study 2- Indolent lymphomas: Follicular lymphoma, grades 1, 2; Extranodal marginal zone B-cell lymphoma of MALT type; Nodal marginal zone B-cell lymphoma; Splenic marginal zone B-cell lymphoma; Small lymphocytic lymphoma
• Study 3- Uncommon lymphomas: Peripheral T cell lymphoma, unspecified; Anaplastic large cell lymphoma (T and null cell type); Lymphoplasmacytic lymphoma (Waldenstrom Macroglobulinemia); Post transplant lymphoproliferative disorders; Mycosis fungoides/Sezary syndrome; Hodgkin Disease; Primary effusion lymphoma; Adult T-cell leukemia/lymphoma; Extranodal NK/T-cell lymphoma, nasal type; Enteropathy-type T-cell lymphoma; Hepatosplenic T-cell lymphoma; Subcutaneous panniculitis-like T-cell lymphoma; Angioimmunoblastic T-cell lymphoma; Anaplastic large cell lymphoma-primary cutaneous type; and Blastic plasmacytoid dendritic cell neoplasm
• Measurable disease by CT or MRI or PET/CT: Must have at least one lesion that has a single diameter of \>= 2 cm or tumor cells in the blood \>= 5 x10\^9/L (Skin lesions can be used if the area is \>= 2 cm in at least one diameter and photographed with a ruler)
• For lymphoplasmacytic lymphoma patients without measurable lymphadenopathy, measurable disease is defined by both of the following criteria: Bone marrow lymphoplasmacytosis with \> 10% lymphoplasmacytic cells or aggregates, sheets, lymphocytes, plasma cells, or lymphoplasmacytic cells on bone marrow biopsy and quantitative IgM monoclonal protein \> 800 mg/dL
• ANC \>= 1200/uL
• Hgb \> 9 g/dl
• PLT \>= 50,000/uL
• Total bilirubin =\< 1.5 x upper limit of normal (ULN) or if total bilirubin is \> 1.5 x ULN the direct bilirubin must be normal
• AST =\< 2.5 x ULN or AST =\< 5 x ULN if liver involvement
• Creatinine =\< 1.5 x ULN
• Creatinine clearance \>= 50mL/min (Cockcroft-Gault calculation)
• Fasting serum cholesterol =\< 300 mg/dL OR =\< 7.75 mmol/L AND fasting triglycerides =\< 2.5 x ULN (NOTE: Lipid lowering medication is allowed)
• ECOG Performance Status (PS) 0, 1, or 2

You may not qualify if:

• Co-morbid systemic illnesses or other severe concurrent disease which, 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
• Active other malignancy, excepting non-melanotic skin cancer or carcinoma-in-situ of the cervix (If there is a history of prior malignancy, they must not be receiving other specific treatment (other than hormonal therapy) for their cancer)
• History of myocardial infarction =\< 6 months, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
• Any of the following because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects; Nursing women; Men or women of childbearing potential who are unwilling to employ adequate contraception throughout the study and for 8 weeks after the last dose of study drug (NOTE: If barrier contraceptives are being used, these must be continued throughout the trial by both sexes; hormonal contraceptives are not acceptable as a sole method of contraception)
• Patients who have received prior treatment with both an mTOR inhibitor (sirolimus, temsirolimus, everolimus) and lenalidomide who did not have a response to either when used as single agents
• Patients with a known allergic reaction to thalidomide, RAD001 (everolimus) or other rapamycins (sirolimus, temsirolimus) or their excipients to the point where either agent should not be given again
• The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs
• Known positive for HIV or infectious hepatitis, type A, B or C
• Patients, who have had a major surgery or significant traumatic injury within 4 weeks of start of study drug, patients who have not recovered from the side effects of any major surgery (defined as requiring general anesthesia) or patients that may require major surgery during the course of the study
• Immunization with attenuated live vaccines within one week of study entry or during study period
• Uncontrolled brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases
• Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of RAD001 (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection)
• Prior Allogeneic Stem Cell Transplant
• No chronic treatment with systemic steroids or another immunosuppressive agents (at a dose equivalent of greater than 20 mg prednisone per day) or other immunosuppressive agents)

Sponsors & Collaborators

• Mayo Clinic: lead

Study Sites (2)

Mayo Clinic in Arizona

Scottsdale, Arizona, 85259, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

MeSH Terms

Conditions

Lymphoma, Extranodal NK-T-Cell; Lymphoma, Large-Cell, Anaplastic; Immunoblastic Lymphadenopathy; Lymphoma, B-Cell, Marginal Zone; Lymphoma, T-Cell, Peripheral; Burkitt Lymphoma; Lymphoma, Large B-Cell, Diffuse; Hodgkin Disease; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma; Lymphoma, Follicular; Lymphoma, Mantle-Cell; Mycosis Fungoides; Sezary Syndrome; Waldenstrom Macroglobulinemia

Interventions

Everolimus; Lenalidomide; Amplified Fragment Length Polymorphism Analysis; Immunohistochemistry; Microarray Analysis; Gene Expression Profiling; In Situ Hybridization, Fluorescence

Condition Hierarchy (Ancestors)

Lymphoma, T-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphadenopathy; Lymphoma, B-Cell; Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Leukemia; Hematologic Diseases; Lymphoma, T-Cell, Cutaneous; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; DNA Fingerprinting; Genetic Techniques; Investigative Techniques; Polymerase Chain Reaction; Nucleic Acid Amplification Techniques; Histocytochemistry; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Histological Techniques; Immunologic Techniques; Microchip Analytical Procedures; In Situ Hybridization; Staining and Labeling; Histocytological Preparation Techniques; Cytogenetic Analysis; Nucleic Acid Hybridization

Results Point of Contact

• Title: Craig B. Reeder MD
• Organization: Mayo Clinic

Reeder.Craig@mayo.edu

480.301.8000

Study Officials

• Craig Reeder, M.D.

  Mayo Clinic

  STUDY CHAIR

• Thomas E. Witzig, M.D.

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

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: February 23, 2010
• First Posted: February 25, 2010
• Study Start: January 10, 2011
• Primary Completion: February 28, 2015
• Study Completion: February 13, 2020
• Last Updated: October 22, 2020
• Results First Posted: March 23, 2020

Record last verified: 2020-09

Locations

US (2)