Clinical trial NCT01782963: Lenalidomide/Bortezomib/Dexamethasone for Multiple Myeloma (MM)
Official title: A Phase II Study of Modified Lenalidomide, Bortezomib and Dexamethasone for Transplant-Ineligible Patients With Newly Diagnosed Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Multiple Myeloma
Keywords: Newly diagnosed
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
First posted: 2013-02-04
Enrollment: 50
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This research study is a Phase II clinical trial. Phase II clinical trials test the effectiveness of an investigational combination of drugs. The purpose is to learn whether the combination of drugs works in treating a specific cancer. "Investigational" means that the combination of drugs is still being studied. It also means that research doctors are trying to find out more about it. Examples of what they want to learn about are the safest dose to use, the side effects it may cause, and if the combination of drugs works for treating different types of cancer.

Detailed description: If you are willing to participate in this study you will be asked to undergo some screening procedures and tests to confirm that you are eligible. Many of these tests and procedures are likely to be part of regular cancer care. They may be done even if it turns out that you do not take part in the research study. If you have had some of these tests or procedures recently, they may or may not have to be repeated. These tests and procedures include: a medical history, physical exam, performance status, vital signs, neurological exam, bone imaging studies, chest x-ray, bone marrow aspirate, ECG, blood tests and urine tests. If these tests show that you are eligible to participate in the research study, you will begin the study treatment. If you do not meet the eligibility criteria, you will not be able to participate in the research study.

For cycles 1-9 (each cycle lasts 35 days) you will receive the following: Lenalidomide-once a day on Days 1-21. You will take Lenalidomide by mouth at the same time each day. Bortezomib- once a day on Days 1, 8, 15 and 22. If you are one of the first ten patients enrolled you will get Bortezomib as an intravenous injection for the first cycle. You will get Bortezomib as an injection under the skin for all other cycles. If you are not one of the first 10 patients enrolled you will get Bortezomib as an injection under the skin for all cycles. Dexamethasone-if you are 75 years old or younger you will get Dexamethasone on Days 1, 2, 8, 9, 15, 16, 22 and 23. If you are more than 75 years old you will get Dexamethasone on Days 1, 8, 15 and 22. You will take Dexamethasone by mouth at the same time each day.

For cycles 10-15 (each cycle lasts 28 days) you will receive the following: Lenalidomide-once a day on Days 1-21. You will take Lenalidomide by mouth at the same time each day. Bortezomib-Once a day on Days 1 and 15. You will get Bortezomib as an injection under the skin. You will be given a drug diary to record taking your doses of the drugs. The study staff will tell you how to complete the diary.

During the study you will have to come to the clinic for visits. The tests and procedures that will be done at each visit are listed below:

Day 1 of all cycles: questions about health, medications etc., physical exam, performance status, vital signs, neurological exam, questionnaires, bone imaging studies, bone marrow aspirate, blood tests, pregnancy test, education and counseling, collection of bone marrow, plasma and serum (cycle 1 only), urine test.

Day 8 of cycles 1-9: questions about health, medications etc., vital signs, blood tests.

Day 15 of all cycles: questions about health, medications, etc., vital signs, blood tests, pregnancy test.

Day 22 of cycles 1-9: questions about health, medications, etc., vital signs, blood tests.

After the final dose of the study drug you will have an End of Treatment visit. The following tests and procedures will be done at this visit: questions about health, medications etc., physical exam, performance status, vital signs, neurological exam, questionnaires, bone imaging studies, bone marrow aspirate, blood tests, pregnancy test, education and counseling, collection of bone marrow, plasma and serum, urine test.

After your End of Treatment visit, we would like to follow your status every 2 months until your disease gets worse. The following tests and procedures will be done at these follow-up visits: questions about health, medications, symptoms etc., blood tests and urine test.

If you are one of the first twenty patients enrolled in the study you will also be asked to provide additional blood samples to study what the body does to the study drug. We will take one sample at five time points during cycle 1 and 2. Collection of these samples may require you to come back into the clinic on additional days when you are not receiving study drugs.

You will be in this research study for about 15 months. You can be in this study for a maximum of 15 cycles. If your disease gets worse before the 15th cycle you will be taken off the study.

Eligibility criteria: Inclusion Criteria:

* Documented symptomatic myeloma, with organ damage related to myeloma
* Myeloma that is measurable either by serum or urine evaluation of the monoclonal component or by assay of serum free light chains
* Must commit to complete abstinence from heterosexual contact or begin two acceptable method of birth control, one highly effective method and one additional effective (barrier) method

Exclusion Criteria:

* Eligible for autologous stem cell transplantation
* HIV positive on combination antiretroviral therapy
* Pregnant or breastfeeding
* Treated with any prior systemic therapy
* Primary amyloidosis or myeloma complicated by amyloidosis
* Receiving other investigational agents within 14 days of the start of this trial or during this trial
* Known brain metastases
* Poor tolerability or known allergy to any of the study drugs or similar compounds
* Intercurrent illness
* Previous history of another malignant condition except for basal cell carcinoma or stage I cervical cancer
* Inability to comply with an anti-thrombotic treatment regimen
* Peripheral neuropathy greater than or equal to grade 2

Primary outcomes:
measure: Objective Response Rate
timeFrame: 2 years
Secondary outcomes:
measure: Number of Participants With Grade 3 or Higher Treatment Related Adverse Events
timeFrame: 2 years
measure: Median Progression Free Survival
timeFrame: From the start of treatment until death or progression or until 3 years after the last participant is enrolled
measure: Median Overall Survival
timeFrame: From the start of treatment until death or until 5 years after the time of disease progression
measure: Median Time to Response
timeFrame: From the start of treatment until the time of first documented response, median duration of 1.1 months
measure: Response Rate With Respect to Cytogenetic Characteristics
timeFrame: 2 years
measure: Mean Plasma Bortezomib Concentration Following Intravenous and and Subcutaneous Injection
timeFrame: Day 1 (5 min, 30min, 5 hours post dose), Days 8, 15, Day 22 (pre dose and 5 min, 30 min, 5 hrs post dose), cycle 2 day 1 pre dose
measure: Pharmacogenomic Markers of Neuropathy
timeFrame: 2 years
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: John Hopkins University
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Danvers
country: United States
facility: Massachusetts General Hospital/North Shore Cancer Center
state: Massachusetts
Study officials:
References: