Study of RAD001 in Patients With Relapsed/Refractory Hodgkin Lymphoma That Has Progressed After High-dose Chemotherapy and Autologous Stem Cell Transplant and/or After Gemcitabine- or Vinorelbine- or Vinblastine-based Treatment.

Study Overview
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Brief Summary
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This study will assess RAD001 in patients with refractory or relapsed Hodgkin Lymphoma that has progressed after high-dose chemotherapy and Autologous Stem cell transplant and/or after gemcitabine- or vinorelbine- or vinblastine-based treatment.

Official Title
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An Open-label, Single-arm Phase II Study of RAD001 in Patients With Relapsed/Refractory Classical Hodgkin Lymphoma

Conditions
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Hodgkin Lymphoma

Intervention / Treatment
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* Drug: Everolimus (RAD001)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with a history of classical Hodgkin's lymphoma that has progressed after high-dose chemotherapy and Autologous Stem cell transplant and/or after gemcitabine- or vinorelbine- or vinblastine-based treatment Patients with at least one site of measurable disease measuring ≥ 2.0cm confirmed by PET and CT Scan (or MRI) Patients with adequate bone marrow, liver and renal function (confirmed by laboratory values) Patients with fasting serum cholesterol ≤300 mg/dL OR ≤7.75 mmol/L AND fasting triglycerides ≤ 2.5 x ULN Exclusion Criteria: Previous treatment with mTOR inhibitors Prior allogeneic stem cell transplant Chemotherapy, monoclonal antibody therapy, major surgery or treatment with other investigational drugs within 4 weeks of starting study treatment Another malignancy within 3 years of study entry (except adequately treated non-melanoma skin cancer and carcinoma in situ of the cervix) Severe and/or uncontrolled medical conditions that could affect participation in this study Female patients who are pregnant or breastfeeding; patients who are not willing to use adequate birth control during the study and for 8 weeks after the last study treatment Other protocol-defined inclusion/exclusion criteria may apply

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RAD001<br>Patients with a history of classical Hodgkin lymphoma (ie, nodular sclerosing, mixed cellularity, lymphocyte-rich, lymphocyte-depleted) whose disease had progressed after receiving high-dose chemotherapy with AHSCT (if eligible) and/or after therapy with a gemcitabine- or vinorelbine- or vinblastine-containing regimen, were enrolled into this study. All patients were assigned to a daily dose of everolimus 10 mg (two 5-mg tablets), selfadministered orally and continuously from Cycle 1 Day 1 (Visit 2) until progression of disease, unacceptable toxicity, death, or discontinuation from the study for any other reason. A treatment cycle consisted of 28 days. | Drug: Everolimus (RAD001)<br>* Everolimus (RAD001) 10 mg (two 5mg tablets) given orally once daily and packed in blisters.<br>* Other names: RAD001;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (ORR) Based on the Assessments by Investigator | ORR: % of patients whose overall disease response was a complete response (CR) or a partial response (PR) in 8 cycles CR: Complete normalization of all index nodal & extranodal lesions: Radiological regression to normal size of all lymph nodes & nodal masses & complete disappearance of all lesions PR: At least a 50% decrease in the SPD of all index nodal & extranodal lesions FDG-avid or PET positive prior to therapy: one or more PET positive at previously involved site.At least a 50% increase in the SPD of all index nodal & extranodal lesions, taking as reference the smallest sum of the product of the diameters of all index lesions recorded at or after baseline . Lesions PET positive if FDG-avid lymphoma or PET positive prior to therapy. Unknown (UNK): Progression not documented & one or more of the index lesions not assessed or assessed using a different method than baseline at the time of radiologic evaluation. Each cycle was 28 days. | at screening and every threee months beginning at cycle 3 until end of treatment due to progression of disease, unacceptable toxicity, death or discontinuation from the study for any other reason | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Overall Response (TTR) Per Kaplan-Meier Estimate | Time to overall response was defined as the time from the first date of treatment to the date of first documented response of CR or PR. Time to overall response is applied to patients whose best overall response is CR or PR. Patients who drop-out or did not have a response (CR or PR) will be treated as censored at the date of last adequate tumor assessment. | Every three months beginning at Cycle 3 until end of treatment due to progression of disease, unacceptable toxicity, death or discontinuation from the study for any other reason | 
| Duration of Overall Response (DoR) | The duration of overall response was calculated from the date of first documented response (CR or PR) to the date of first documented disease progression or death due to any cause or start of a new antineoplastic therapy. This only applies to patients whose best overall response is CR or PR. | Every three months beginning at Cycle 3 until end of treatment due to progression of disease, unacceptable toxicity, death or discontinuation from the study for any other reason | 
| Disease Control Rate (DCR) | The disease control rate was defined as the percentage of patients with a best overall response of CR, PR or stable disease (SD). | Every three months beginning at Cycle 3 until end of treatment due to progression of disease, unacceptable toxicity, death or discontinuation from the study for any other reason | 
| Duration of Disease Control | The duration of overall response (CR/PR) was applied only to patients whose best overall response was CR or PR. Duration of overall response was calculated from the date of the first documented response of CR or PR to the date of first documented disease progression or death due to any cause or start of a new antineoplastic therapy. | Every three months beginning at Cycle 3 until end of treatment due to progression of disease, unacceptable toxicity, death or discontinuation from the study for any other reason | 
| Progression Free Survival (PFS) by Kaplan-Meier Estimate | Progression-free survival (PFS) was defined as the time from the first date of treatment to the date of first documented disease progression or death due to any cause or start of a new antineoplastic therapy. An event for PFS was defined as a documented disease progression or death due to any cause or start of a new antineoplastic therapy, whichever occurred first. Cycle = 28 days. | Every three months beginning at Cycle 3 until end of treatment due to progression of disease, unacceptable toxicity, death or discontinuation from the study for any other reason | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hodgkin's Lymphoma, Hodgkin Lymphoma, Hodgkin's Disease, Hodgkin Disease, Lymphoma, Lymphoproliferative Disorders, Neoplasms by Histological type, Lymphatic Diseases, Hemic and Lymphatic Diseases, Recurrent Lymphoma, Refractory Lymphoma, Relapsed Lymphoma, Classical Hodgkin Lymphoma, Classical Hodgkin's Disease, Nodular sclerosing Hodgkin Lymphoma, Mixed-cellularity Hodgkin Lymphoma, Lymphocyte-rich Hodgkin Lymphoma, Lymphocyte depleted Hodgkin Lymphoma