RAD001 and Lenalidomide in the Treatment of Subjects With Relapsed and Relapsed/Refractory Multiple Myeloma
Primary Purpose
Multiple Myeloma
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
RAD001
lenalidomide
Sponsored by
About this trial
This is an interventional treatment trial for Multiple Myeloma focused on measuring relapsed multiple myeloma, refractory multiple myeloma, RAD001, lenalidomide
Eligibility Criteria
Inclusion Criteria:
- Subject was previously diagnosed with multiple myeloma bases on standard criteria listed in protocol
- Patients must have relapsed or relapsed/refractory disease
- 18 years of age or older
- All necessary baseline studies for determining eligibility must be obtained within 21 days prior to enrollment
- ECOG Performance Status of 0 to 2
- Able to take aspirin (81 or 325mg) daily as prophylactic anticoagulation
- Prior thalidomide/lenalidomide therapy is allowed
- Able to take bactrim
- Female of childbearing potential must have a negative serum or urine pregnancy test
Exclusion Criteria:
- Renal insufficiency
- Concommitant therapy medications that include corticosteroids or other chemotherapy that is or may be active against myeloma or therapy with chemotherapy within 2 weeks prior to day 1. Nitrosoureas must be discontinued 6 weeks prior to day 1. Concurrent radiation therapy is not permitted.
- Subjects with evidence of mucosal or internal bleeding and/or platelet refractory
- Subjects with poorly controlled diabetes mellitus
- Subjects with an ANC < 10-00 cells/mm3
- Subjects with a hemoglobin < 8.0 g/Dl
- AST (SGOT and ALT (SGPT) greater or equal to 2x ULN
- Prior therapy with RAD001
- Known hypersensitivity to thalidomide or lenalidomide
- Any condition, including laboratory abnormalities, that in the opinion of the Investigator, places the subject at unacceptable risk if he/she were to participate in the study
- Clinically relevant active infection or serious co-morbid medical conditions such as recent thromboembolic disease are ineligible if occurred less than 2 weeks prior to enrollment or clinically unstable
- Chronic obstructive or chronic restrictive pulmonary disease, difficult to control diabetes, upper gastrointestinal ulceration, and cirrhosis
- Prior malignancy (within the last 3 years) except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, in situ breast cancer, in situ prostate cancer or other cancer for which the subject has been disease-free for at least 3 years
- Pregnant or breast-feeding females
- Prior treatment with any investigational drug within preceding 4 weeks
- Major surgery, and or radiation with 2 weeks of study initiation
- Uncontrolled leptomeningeal disease
- Prior treatment with other mTOR inhibitors
- The use of G-CSF is not permitted to render the patient eligible fot the study
- POEMS syndrome
- Known HIV infection
- Known active Hepatitis B or C infection
- Myocardial infarction within 6 months prior to enrollment or has NYHA Class III or IV heart failure, uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities
- Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of RAD001
- Patients with active, bleeding diathesis or on oral anti-vitamin K medication
Sites / Locations
- Massachusetts General Hospital
- Dana-Farber Cancer Institute
- Mayo Clinic
- Memorial Sloan-Kettering Cancer Center
- Medical College of Wisconsin
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Single arm
Arm Description
Single arm phase I study
Outcomes
Primary Outcome Measures
To evaluate the safety of RAD001 when given in combination with lenalidomide and to identify the maximum tolerated dose (MTD) as well as a recommended Phase 2 dose for the combination in this patient population.
Secondary Outcome Measures
To evaluate the response to the combination of RAD001 and lenalidomide in subjects with multiple myeloma.
To determine the pharmacokinetics of RAD001 and lenalidomide.
To identify possible surrogate markers to better define mechanisms of action for the combination of the two drugs.
Full Information
NCT ID
NCT00729638
First Posted
August 4, 2008
Last Updated
August 7, 2014
Sponsor
Massachusetts General Hospital
Collaborators
Dana-Farber Cancer Institute, Brigham and Women's Hospital, Mayo Clinic, Memorial Sloan Kettering Cancer Center, Medical College of Wisconsin
1. Study Identification
Unique Protocol Identification Number
NCT00729638
Brief Title
RAD001 and Lenalidomide in the Treatment of Subjects With Relapsed and Relapsed/Refractory Multiple Myeloma
Official Title
An Open-Label Phase I Study of the Safety of and Efficacy of RAD001 in Combination With Lenalidomide in the Treatment of Subjects With Relapsed and Relapsed/Refractory Multiple Myeloma
Study Type
Interventional
2. Study Status
Record Verification Date
August 2014
Overall Recruitment Status
Completed
Study Start Date
June 2008 (undefined)
Primary Completion Date
November 2009 (Actual)
Study Completion Date
November 2009 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Massachusetts General Hospital
Collaborators
Dana-Farber Cancer Institute, Brigham and Women's Hospital, Mayo Clinic, Memorial Sloan Kettering Cancer Center, Medical College of Wisconsin
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this research study is to determine the highest dose of lenalidomide and RAD001 that can be given without causing too many serious side effects. Another goal of this research study is to look at how the participants cancer may respond to the study treatment. Additionally, we wish to learn more about how the body breaks down and gets rid of the study drugs. We will also try to find substances in the blood (biomarkers) that may help predict how myeloma will respond to study treatment.
Detailed Description
Researchers are looking for the highest doses of RAD001 and lenalidomide used in combination that can be given safely so small groups of people will be enrolled in steps in this trial. The first group will be given a certain dose of RAD001 and a certain dose of lenalidomide. If they have few or manageable side effects, the next small group of people will be enrolled with a higher dose of RAD001 and/or a higher dose of lenalidomide. This will continue until the highest dose of the drugs used is determined.
Study treatment will be given in 28 day cycles. Both RAD001 and lenalidomide are pills that are taken orally. Both drugs will be started on the same day. RAD001 will be taken either every other day or every day for the first 3 weeks (days 1-21) of each 28-day cycle. Lenalidomide will be taken daily for the first 3 weeks (days 1-21) of each cycle.
Participants will come to the clinic weekly during the first cycle to monitor side effects. The following will be performed at these clinic visits: physical examination, medical history update, questionnaires, and blood work.
On cycles 2-8, participants will come to the clinic on Day 1 of each cycle. The following will be performed at this clinic visit: physical examination, medical history update, questionnaire, and blood word.
At the end of cycle 8, a skeletal survey, bone marrow aspiration and biopsy will be performed to check response to study treatment.
Participants may continue to receive RAD001 and lenalidomide beyond 8 cycles if their cancer does not get worse and they do not have unacceptable side effects.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma
Keywords
relapsed multiple myeloma, refractory multiple myeloma, RAD001, lenalidomide
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
28 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Single arm
Arm Type
Experimental
Arm Description
Single arm phase I study
Intervention Type
Drug
Intervention Name(s)
RAD001
Intervention Description
Dose levels will change: Taken orally either every other day for the first three weeks of each cycle or taken every day for the first three weeks of each cycle.
Intervention Type
Drug
Intervention Name(s)
lenalidomide
Intervention Description
Dose level will vary: taken orally 30-60 minutes after taking RAD001 every day for the first three weeks of each cycle.
Primary Outcome Measure Information:
Title
To evaluate the safety of RAD001 when given in combination with lenalidomide and to identify the maximum tolerated dose (MTD) as well as a recommended Phase 2 dose for the combination in this patient population.
Time Frame
2 years
Secondary Outcome Measure Information:
Title
To evaluate the response to the combination of RAD001 and lenalidomide in subjects with multiple myeloma.
Time Frame
2 years
Title
To determine the pharmacokinetics of RAD001 and lenalidomide.
Time Frame
2 years
Title
To identify possible surrogate markers to better define mechanisms of action for the combination of the two drugs.
Time Frame
2 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Subject was previously diagnosed with multiple myeloma bases on standard criteria listed in protocol
Patients must have relapsed or relapsed/refractory disease
18 years of age or older
All necessary baseline studies for determining eligibility must be obtained within 21 days prior to enrollment
ECOG Performance Status of 0 to 2
Able to take aspirin (81 or 325mg) daily as prophylactic anticoagulation
Prior thalidomide/lenalidomide therapy is allowed
Able to take bactrim
Female of childbearing potential must have a negative serum or urine pregnancy test
Exclusion Criteria:
Renal insufficiency
Concommitant therapy medications that include corticosteroids or other chemotherapy that is or may be active against myeloma or therapy with chemotherapy within 2 weeks prior to day 1. Nitrosoureas must be discontinued 6 weeks prior to day 1. Concurrent radiation therapy is not permitted.
Subjects with evidence of mucosal or internal bleeding and/or platelet refractory
Subjects with poorly controlled diabetes mellitus
Subjects with an ANC < 10-00 cells/mm3
Subjects with a hemoglobin < 8.0 g/Dl
AST (SGOT and ALT (SGPT) greater or equal to 2x ULN
Prior therapy with RAD001
Known hypersensitivity to thalidomide or lenalidomide
Any condition, including laboratory abnormalities, that in the opinion of the Investigator, places the subject at unacceptable risk if he/she were to participate in the study
Clinically relevant active infection or serious co-morbid medical conditions such as recent thromboembolic disease are ineligible if occurred less than 2 weeks prior to enrollment or clinically unstable
Chronic obstructive or chronic restrictive pulmonary disease, difficult to control diabetes, upper gastrointestinal ulceration, and cirrhosis
Prior malignancy (within the last 3 years) except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, in situ breast cancer, in situ prostate cancer or other cancer for which the subject has been disease-free for at least 3 years
Pregnant or breast-feeding females
Prior treatment with any investigational drug within preceding 4 weeks
Major surgery, and or radiation with 2 weeks of study initiation
Uncontrolled leptomeningeal disease
Prior treatment with other mTOR inhibitors
The use of G-CSF is not permitted to render the patient eligible fot the study
POEMS syndrome
Known HIV infection
Known active Hepatitis B or C infection
Myocardial infarction within 6 months prior to enrollment or has NYHA Class III or IV heart failure, uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities
Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of RAD001
Patients with active, bleeding diathesis or on oral anti-vitamin K medication
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Noopur Raje, MD
Organizational Affiliation
Massachusetts General Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Dana-Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
Memorial Sloan-Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
Medical College of Wisconsin
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226'
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
24761838
Citation
Yee AJ, Hari P, Marcheselli R, Mahindra AK, Cirstea DD, Scullen TA, Burke JN, Rodig SJ, Hideshima T, Laubach JP, Ghobrial IM, Schlossman RL, Munshi NC, Anderson KC, Weller EA, Richardson PG, Raje NS. Outcomes in patients with relapsed or refractory multiple myeloma in a phase I study of everolimus in combination with lenalidomide. Br J Haematol. 2014 Aug;166(3):401-9. doi: 10.1111/bjh.12909. Epub 2014 Apr 25.
Results Reference
result
Learn more about this trial
RAD001 and Lenalidomide in the Treatment of Subjects With Relapsed and Relapsed/Refractory Multiple Myeloma
We'll reach out to this number within 24 hrs