An open-label, single-arm phase II study of everolimus (RAD001) in patients with relapsed/refractory classical Hodgkin lymphoma
Michelle A. Fanale
The goal of this clinical research study is to learn if everolimus can help to control Hodgkin lymphoma. The safety of this drug will also be studied.
Disease Group: Lymphoma
Treatment Agent: Everolimus,RAD001
Treatment Location: Both at MDACC & and Other Sites
Primary objectives To determine the objective response rate to therapy with 10 mg everolimus in patients with refractory/relapsed classical Hodgkin lymphoma (HL) (determined by Positron Emission Tomography PET and computer tomography CT scans). Secondary objectives To assess the time to response To assess the duration of response To determine the disease control rate (complete response (CR), partial response (PR), and stable disease (SD)) To evaluate progression-free survival and overall survival To determine the safety and tolerability of 10 mg qd everolimus monotherapy
IRB Review and Approval Date: 08/30/2010
Recruitment Status: Not Accepting
Projected Accrual: 54
1) Age >/= 18 years
2) Eastern Cooperative Oncology Group (ECOG) performance status of </= 2
3) History of classical Hodgkin lymphoma (i.e. Nodular sclerosing, Mixed-cellularity, Lymphocyte-rich, Lymphocyte depleted) that has progressed after receiving high dose chemotherapy with AHSCT (if eligible) and/or after therapy with a gemcitabine- or vinorelbine- or vinblastine-containing regimen. Note: A bone marrow biopsy is required within 3 months of study entry for all patients regardless of bone marrow status. For all patients with confirmed bone marrow involvement at study entry, a follow - up bone marrow biopsy is required at the time of Complete Response.
4) At least one site of measurable disease at baseline >/= 2.0 cm in the longest transverse diameter and clearly measurable in at least two perpendicular dimensions, as determined by PET and CT scan (MRI is allowed only if CT scan can not be performed). Note: Patients with bone marrow involvement are eligible, but these criteria alone may not be used for disease measurement.
5) Patient has the following laboratory values: • Absolute neutrophil count (ANC) >/= 1.0 x 10 9/L [SI units 1.0 x 109/L] • Platelet count >/= 75 x 109/L • Serum creatinine </= 1.5 x ULN • Serum bilirubin </= 1.5 x ULN (or </= 3.0 x ULN, if patient has Gilbert syndrome) • AST/SGOT and/or ALT/SGPT </= 2.5 x upper limit of normal (ULN) or </= 5.0 x ULN if the transaminase elevation is due to disease involvement • 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.
6) Written informed consent was obtained from the patient prior to any study-specific screening procedures
7) Patient has the ability to swallow tablets
1) Prior treatment with an mTOR inhibitor (e.g., sirolimus,
2) Treatment with monoclonal antibody therapy (e.g., rituximab or anti CD-30 antibody, etc.) within 4 weeks of start of study treatment
3) Patient has received chemotherapy or any investigational drug or undergone major surgery </= 4 weeks prior to starting study drug and/or the side effects of such therapy have not resolved to </= grade 1
4) Patient has received prior radiation therapy </= 4 weeks or limited field radiotherapy </= 2 weeks prior to start of study treatment or whose side effects of such therapy have not resolved to </= grade 1
5) Patient is using any anti-cancer therapy concomitantly
6) Patient has been treated with allogeneic hematopoietic stem cell transplant
7) Patient has a history of another primary malignancy </= 3 years before study entry, with the exception of adequately treated non-melanoma skin cancer, and carcinoma in situ of uterine cervix
8) Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as: • Symptomatic congestive heart failure of New York Heart Association Class III or IV • unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction within 6 months of start of study drug, serious uncontrolled cardiac arrhythmia or any other clinically significant cardiac disease • severely impaired lung function as defined as spirometry and DLCO that is less than 50% of the normal predicted value and/or 02 saturation that is 88% or less at rest on room air • uncontrolled diabetes as defined by fasting serum glucose >1.5 x ULN (Note: Optimal glycemic control should be achieved before starting everolimus) • active (acute or chronic) or uncontrolled severe infections
9) Liver disease such as cirrhosis and/or severe hepatic impairment (Child-Pugh class C). Note: A detailed assessment of Hepatitis B/C medical history and risk factors must be done for all patients at screening. hepatitis B virus-deoxyribonucleic Acid (HBV-DNA), hepatitis B surface antigen (HBsAg), hepatitis B surface antibodies (HBs Ab), and HBc Ab and hepatitis C virus ribonucleic acid polymerase chain reaction (HCV RNA PCR) testing are required at screening for all patients with a positive medical history based on risk factors and/or confirmation of prior HBV/HCV infection.
10) Patient has an impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of everolimus (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, obstruction, or stomach and/or small bowel resection)
11) Patient has a known history of human immunodeficiency virus (HIV) seropositivity. HIV testing is not required at screening.
12) Female patients who are pregnant or breast feeding, or adults of reproductive potential who 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, by both sexes. (Women of childbearing potential must have a negative serum pregnancy test within 7 days prior to administration of everolimus)
13) Male patients whose sexual partner(s) are Women of Childbearing potential (WOCBP) who are not willing to use adequate contraception, during the study and for 8 weeks after the end of treatment
14) Patients receiving chronic, systemic treatment with corticosteroids at a dose equivalent of greater than 20 mg prednisone per day or another immunosuppressive agent. Topical or inhaled corticosteroids are allowed.
15) Patients who have received immunization with attenuated live vaccines within one week of study entry or during study period (Note: 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.
16) Patients with a known hypersensitivity to everolimus or other rapamycins (sirolimus, temsirolimus) or to its excipients
17) Patients with a history of noncompliance to medical regimens
18) Patients unwilling to or unable to comply with the protocol
Information and next steps
Michelle A. Fanale
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