Everolimus (RAD001) in Primary Therapy of Waldenstrom's Macroglobulinemia

NCT00976248 | Completed Phase 2 Results DMC

• 1 other identifier: 09-214
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this research study is to determine the safety of RAD001(Everolimus) and the highest dose of this drug that can be given to people safely. RAD001(Everolimus) is a drug that works by preventing cells in the body from growing and dividing. Information from basic and Phase I clinical research studies suggests that RAD001 also may help to prevent tumor growth in people with relapsed or refractory lymphoma.

Conditions

Waldenstrom's Macroglobulinemia

Keywords

everolimus; RAD001; WM

Outcome Measures

Primary Outcomes (3)

• Overall Response Rate of RAD001 in Patients With Previously Untreated WM

  Overall Response = Complete Response + Near Complete Response + Very Good Partial Response + Partial Response + Minor Response Complete Response: resolution of all symptoms, normalization of serum IgM levels with complete disappearance of IgM paraprotein by immunofixation, and resolution of any adenopathy or splenomegaly. A near CR (nCR) is defined as fulfilling all CR criteria in the presence of positive immunofixation test for an IgM paraprotein. Very Good Partial Response: \> 90% reduction in serum IgM levels. Partial Response: \> 50% reduction in serum IgM levels. Minor Response: 25-49% reduction in serum IgM levels Progressive Disease: greater than 25% increase in serum IgM level occurs from the lowest attained response value or progression of clinically significant disease related symptom(s). Stable Disease: \< 25% change in serum IgM levels, in the absence of new or increasing adenopathy or splenomegaly and/or other progressive signs or symptoms of WM

  End of Treatment, an average of 16 months

• Time to Progression With Single Agent RAD001 Therapy in Previously Untreated WM.

  Progression is defined as a 25% increase in serum IgM from the lowest attained response value or progression of clinically significant disease related symptoms.

  End of Treatment, an average of 16 months

• Time to Next Therapy With Single Agent RAD001 Therapy in Previously Untreated WM

  End of follow-up, an average of 18 months

Study Arms (1)

RAD001

EXPERIMENTAL

RAD001, oral, 10 mg, daily

Drug: RAD001

Interventions

RAD001 DRUG

Taken orally once a day

Also known as: Everolimus

RAD001

Eligibility Criteria

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

You may qualify if:

• years of age or older
• Adequate liver and renal function as outlined in the protocol
• Fasting serum cholesterol 300mg/dl or less OR 7.75mmol/L or less AND fasting triglycerides 2.5 x institutional ULN or less.
• Clinicopathological diagnosis of Waldenstrom's macroglobulinemia as defined by consensus panel of the Second International Workshop on Waldenstrom's macroglobulinemia
• No previous therapy for WM
• Measurable disease, defined as presence of immunoglobulin M (IgM) paraprotein with a minimum IgM level of 2 times the upper limit of each institution's normal value or greater is required
• ECOG Performance status of 0-2
• Patients must have a life expectancy of at least 3 months
• Baseline platelet and absolute neutrophil as outlined in the protocol
• INR and PTT 1.5 x normalized ratio or less
• A male subject agrees to use an acceptable method for contraception for the duration of study and for 8 weeks after the last dose of the study drug
• Female subject either post-menopausal or surgically sterilized or willing to use acceptable methods of birth control for the duration of the study and for 8 weeks after the last dose of study drug

You may not qualify if:

• Patients experiencing symptomatic hyperviscosity and requiring plasmapheresis. This includes any patient who, in the judgement of the investigator requires urgent response and will not be eligible. These patients have hyperviscosity which includes serum IgM levels of 5000 mg/dL or greater. Symptoms may include nosebleeds, visual complications, fatigue, headaches, confusion, etc.
• 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 or patients that may require major surgery during the course of the study.
• Patients receiving chronic, systemic treatment with corticosteroids or another immunosuppressive agent. Topical or inhaled corticosteroids are allowed.
• Patients should not receive any immunization with attenuated live vaccines within one week of study entry or during study period.
• Patients who have had any severe and/or uncontrolled medical conditions or other conditions that would affect their participation in the study.
• Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of RAD001.
• Female patients that are pregnant or breast feeding, or adults of reproductive potential who are not using effective birth control methods.
• Patients with known hypersensitivity to RAD001 or other rapamycins or to its excipients
• Patients with other malignancies within the past 3 years except for adequately treated carcinoma of the cervix or basal or squamous cell of the skin
• Patients with known history of HIV seropositivity
• History of noncompliance to medical regimens
• Patients unwilling to or unable to comply with the protocol

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Brigham and Women's Hospital: collaborator
• Novartis: collaborator

Study Sites (1)

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Related Publications (3)

• Treon SP, Tripsas CK, Ioakimidis L, Warren D, Patterson C, Heffner L, Eradat H, Gregory SA, Thomas S, Advani R, Baz R, Badros, Ashraf Z, Matous J, Anderson KC, Ghobrial IM Prospective, Multicenter Study of the MTOR Inhibitor Everolimus (RAD001) As Primary Therapy in Waldenstrom's Macroglobulinemia ASH Annual Meeting Abstracts 2011 118: 2951

  RESULT

• Treon SP, Tripsas CK, Meid K, Patterson CJ, Heffner H, Gregory SA, Thomas SK, Advani RH, Baz R, Badros AZ, Matous J, Murphy TJ, Ghobrial IM. Prospective, Multicenter Study Of The MTOR Inhibitor Everolimus (RAD001) As Primary Therapy In Waldenstrom's Macroglobulinemia Blood 2013 122:1822.

  RESULT

• Treon SP, Meid K, Tripsas C, Heffner LT, Eradat H, Badros AZ, Xu L, Hunter ZR, Yang G, Patterson CJ, Gustine J, Castillo JJ, Matous J, Ghobrial IM. Prospective, Multicenter Clinical Trial of Everolimus as Primary Therapy in Waldenstrom Macroglobulinemia (WMCTG 09-214). Clin Cancer Res. 2017 May 15;23(10):2400-2404. doi: 10.1158/1078-0432.CCR-16-1918. Epub 2016 Nov 11.

  PMID: 27836860 DERIVED

MeSH Terms

Conditions

Waldenstrom Macroglobulinemia

Interventions

Everolimus

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals

Results Point of Contact

• Title: Steven P. Treon, MD, PhD
• Organization: Dana-Farber Cancer Institute

steven_treon@dfci.harvard.edu

617-632-2681

Study Officials

• Steven Treon, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Bing Center

Study Record Dates

• First Submitted: September 11, 2009
• First Posted: September 14, 2009
• Study Start: November 1, 2009
• Primary Completion: July 1, 2016
• Study Completion: July 1, 2018
• Last Updated: October 3, 2018
• Results First Posted: June 16, 2014

Record last verified: 2018-09

Locations

US (1)