Multiple MyelomaPhase 1NCT00729638
RAD001 and Lenalidomide in the Treatment of Subjects With Relapsed and Relapsed/Refractory Multiple Myeloma
A Phase 1 study testing RAD001 and lenalidomide in people with Multiple Myeloma, run by Massachusetts General Hospital at 5 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Multiple Myeloma
- What is being tested?
- RAD001 and lenalidomide
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 28 participants
- Where
- 5 sitesUnited States
- Study dates
- Jun 2008to Nov 2009
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- Prior thalidomide/lenalidomide therapy is allowed
- Able to take bactrim
- Female of childbearing potential must have a negative serum or urine pregnancy test
Who cannot join
- 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
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- 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
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
Massachusetts General Hospital
Boston, Massachusetts, 02114
Dana-Farber Cancer Institute
Boston, Massachusetts, 02115
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226'
Memorial Sloan-Kettering Cancer Center
New York, New York, 10021
Mayo Clinic
Rochester, Minnesota, 55905
About this study
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
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.
Read the 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.
- Conditions
- Multiple Myeloma
- Being tested
- RAD001, lenalidomide
- Keywords
- relapsed multiple myeloma, refractory multiple myeloma, RAD001, lenalidomide
- Medical subject headings
- Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RAD001Drug
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.
lenalidomideDrug
Dose level will vary: taken orally 30-60 minutes after taking RAD001 every day for the first three weeks of each cycle.
| Study group | Role | What they receive |
|---|---|---|
| Single arm | Experimental | Single arm phase I study Receives: Drug: RAD001; Drug: lenalidomide |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 2 years
Secondary outcomes (3)
To evaluate the response to the combination of RAD001 and lenalidomide in subjects with multiple myeloma.
Measured: 2 years
To determine the pharmacokinetics of RAD001 and lenalidomide.
Measured: 2 years
To identify possible surrogate markers to better define mechanisms of action for the combination of the two drugs.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Aug 2008 (estimated)
- Study startJun 2008
- Primary completionNov 2009
- Study completionNov 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Multiple MyelomaStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 28 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Dana-Farber Cancer Institute, Brigham and Women's Hospital, Mayo Clinic, Memorial Sloan Kettering Cancer Center, Medical College of Wisconsin
- Responsible party
- Principal investigator, Noopur Raje, Massachusetts General Hospital
- Investigators
- Noopur Raje, MD, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00729638
- Sponsor's protocol ID
- 07-288
- Other IDs
- RV-MM-PI-142
- Status last verified
- Aug 2014
- First submitted
- 4 Aug 2008
- Last updated
- 11 Aug 2014
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 24761838
Study at a glance
From the registry record, last updated by the sponsor on 11 Aug 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00729638
- Acronym / sponsor ID
- 07-288
- Conditions
- Multiple Myeloma
- Keywords
- relapsed multiple myeloma, refractory multiple myeloma, RAD001, lenalidomide
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 28 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Collaborators
- Dana-Farber Cancer Institute, Brigham and Women's Hospital, Mayo Clinic, Memorial Sloan Kettering Cancer Center, Medical College of Wisconsin
- Study start
- Jun 2008
- Primary completion
- Nov 2009 (actual)
- Study completion
- Nov 2009 (actual)
- First posted
- 7 Aug 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Single arm | Experimental | Drug: RAD001, Drug: lenalidomideSingle arm phase I study |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (25 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RAD001Dose 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. | Drug | Single arm |
| lenalidomideDose level will vary: taken orally 30-60 minutes after taking RAD001 every day for the first three weeks of each cycle. | Drug | Single arm |
Primary outcome
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
3 secondary outcomes
To evaluate the response to the combination of RAD001 and lenalidomide in subjects with multiple myeloma.
Time frame: 2 years
To determine the pharmacokinetics of RAD001 and lenalidomide.
Time frame: 2 years
To identify possible surrogate markers to better define mechanisms of action for the combination of the two drugs.
Time frame: 2 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Aug 2014.
- Results publication: PubMed 24761838Yee 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Noopur Raje, MD principal investigator
Massachusetts General Hospital
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing RAD001 and lenalidomide in people with Multiple Myeloma, run by Massachusetts General Hospital at 5 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Aug 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00729638, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Aug 2014.