Brief Title
Everolimus and Lenalidomide in Treating Patients With Relapsed or Refractory Non-Hodgkin or Hodgkin Lymphoma
Official Title
A Phase I/II Clinical Trial of the mTor Inhibitor RAD001 (Everolimus) in Combination With Lenalidomide (Revlimid) for Patients With Relapsed or Refractory Lymphoid Malignancy
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.
Detailed Description
PRIMARY OBJECTIVES:
I.Phase I: To establish the maximum tolerated dose of EVEROLIMUS and lenalidomide in subjects
with relapsed/refractory Non-Hodgkin Lymphoma or Hodgkin Lymphoma.
II. Phase II: To assess tumor response to EVEROLIMUS and lenalidomide in subjects with
relapsed/refractory Non-Hodgkin Lymphoma or Hodgkin Lymphoma.
SECONDARY OBJECTIVES:
I. To evaluate overall survival, progression-free survival, duration of response, and time to
treatment failure of subjects receiving EVEROLIMUS and lenalidomide.
II. To describe the adverse event profile (using CTCAE CTEP Version 4.0) of EVEROLIMUS and
lenalidomide.
OUTLINE: 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.
After completion of study treatment, patients are followed periodically.
Study Phase
Phase 1/Phase 2
Study Type
Interventional
Primary Outcome
Number of Patients Reporting Dose-Limiting Toxicity (DLT) (Phase I)
Secondary Outcome
Overall Survival for All Eligible Patients
Condition
Adult Nasal Type Extranodal NK/T-cell Lymphoma
Intervention
everolimus
Study Arms / Comparison Groups
Arm I
Description: 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.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
58
Start Date
January 10, 2011
Completion Date
February 13, 2020
Primary Completion Date
February 28, 2015
Eligibility Criteria
Inclusion
- 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
- Females of childbearing potential (FCBP) must have a negative serum pregnancy test
with a sensitivity of at least 50 IU/ml within 10-14 days prior to and again within 24
hours of starting lenalidomide and must either commit to continued abstinence from
heterosexual intercourse or begin TWO acceptable methods of birth control, one highly
effective method and one additional effective method AT THE SAME TIME, at least 28
days before she starts taking lenalidomide, during study treatment and for 8 weeks
after the last dose of RAD001 (FCBP must also agree to ongoing pregnancy testing)
- Men must agree to use a latex condom during sexual contact with a FCBP even if they
have had a successful vasectomy (All patients must be counseled at a minimum of every
28 days about pregnancy precautions and risks of fetal exposure)
- Provide informed written consent
- Willingness to return to Mayo Clinic enrolling institution for follow-up
- Patient is willing to provide blood samples for research purposes
- Recovered from acute side effects of prior myelosuppressive chemotherapy or biological
therapy
- All study participants must be registered into the mandatory RevAssist program, and be
willing and able to comply with the requirements of RevAssist
Exclusion
- 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)
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Craig Reeder, M.D., ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT01075321
Organization ID
MC0981
Secondary IDs
NCI-2010-00235
Responsible Party
Sponsor
Study Sponsor
Mayo Clinic
Study Sponsor
Craig Reeder, M.D., Study Chair, Mayo Clinic
Verification Date
September 2020