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.

• ClinicalTrials.gov Identifier: NCT01022996
• Recruitment Status: Completed
• First Posted: December 1, 2009
• Results First Posted: April 6, 2016
• Last Update Posted: May 18, 2016
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Hodgkin Lymphoma	Drug: Everolimus (RAD001)	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 57 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-label, Single-arm Phase II Study of RAD001 in Patients With Relapsed/Refractory Classical Hodgkin Lymphoma
• Study Start Date: December 2009
• Actual Primary Completion Date: November 2014
• Actual Study Completion Date: November 2014

Arms and Interventions

Arm

Intervention/treatment

Experimental: RAD001; 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); Everolimus (RAD001) 10 mg (two 5mg tablets) given orally once daily and packed in blisters.; Other Name: RAD001

Outcome Measures

Primary Outcome Measures :

1. Overall Response Rate (ORR) Based on the Assessments by Investigator [ Time Frame: 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 ]
   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.

Secondary Outcome Measures :

1. Time to Overall Response (TTR) Per Kaplan-Meier Estimate [ Time Frame: 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 ]
   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.
2. Duration of Overall Response (DoR) [ Time Frame: 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 ]
   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.
3. Disease Control Rate (DCR) [ Time Frame: 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 ]
   The disease control rate was defined as the percentage of patients with a best overall response of CR, PR or stable disease (SD).
4. Duration of Disease Control [ Time Frame: 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 ]
   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.
5. Progression Free Survival (PFS) by Kaplan-Meier Estimate [ Time Frame: 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) 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, California

University of California at Los Angeles UCLS School of Medicine

Los Angeles, California, United States, 90095

United States, Colorado

Rocky Mountain Cancer Centers RMCC - Aurora

Greenwood Village, Colorado, United States

United States, Florida

MD Anderson Cancer Center - Orlando

Orlando, Florida, United States, 32806

United States, Georgia

Emory University School of Medicine/Winship Cancer Institute Emory University Med School

Atlanta, Georgia, United States, 30322

United States, Illinois

Lurie Children's Hospital of Chicago Robert H. Lurie Comp Cancer

Chicago, Illinois, United States, 60611

United States, Indiana

Indiana University Simon Cancer Center

Indianapolis, Indiana, United States, 46202

United States, Massachusetts

Dana Farber Cancer Institute

Boston, Massachusetts, United States, 02115

United States, Michigan

Karmanos Cancer Institute Karmanos-1

Detroit, Michigan, United States, 48201

United States, Minnesota

Mayo Clinic - Rochester Mayo Lymphoma Group

Rochester, Minnesota, United States, 55905

United States, Missouri

Washington University School Of Medicine-Siteman Cancer Ctr StudyCoordinator:CLBH589B2201

St. Louis, Missouri, United States, 63110

United States, New York

New York Presbyterian Hospital Weill Cornell Med Ctr

New York, New York, United States, 10021

United States, North Carolina

Duke University Medical Center Duke University Medical Ctr

Durham, North Carolina, United States, 27710

United States, Tennessee

University of Tennessee Cancer Institute Univ Tennessee Cancer

Memphis, Tennessee, United States, 38104

United States, Texas

University of Texas/MD Anderson Cancer Center Dept.ofMDAndersonCancerCtr(3)

Houston, Texas, United States, 77030-4009

United States, Wisconsin

University of Wisconsin Comprehensive Cancer Center Clinical Science Center - H4

Madison, Wisconsin, United States, 53792

Medical College of Wisconsin

Milwaukee, Wisconsin, United States, 53226

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals; Novartis Pharmaceuticals

More Information

Additional Information:

Related Info 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Johnston PB, Pinter-Brown LC, Warsi G, White K, Ramchandren R. Phase 2 study of everolimus for relapsed or refractory classical Hodgkin lymphoma. Exp Hematol Oncol. 2018 May 11;7:12. doi: 10.1186/s40164-018-0103-z. eCollection 2018.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT01022996
• Other Study ID Numbers: CRAD001NUS65
• First Posted: December 1, 2009
• Results First Posted: April 6, 2016
• Last Update Posted: May 18, 2016
• Last Verified: April 2016

Keywords provided by Novartis ( Novartis Pharmaceuticals ):

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

Additional relevant MeSH terms:

Lymphoma; Hodgkin Disease; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Everolimus; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs