Study to Evaluate Two Lenalidomide Dose Regimens With Low Dose Dexamethasone for the Treatment Relapsed Multiple Myeloma
| Status: | Active, not recruiting |
|---|---|
| Conditions: | Blood Cancer, Hematology |
| Therapuetic Areas: | Hematology, Oncology |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 4/21/2016 |
| Start Date: | August 2010 |
| End Date: | December 2016 |
A Controlled, Parallel-Group, Randomized, Open-Label Study to Evaluate Two Lenalidomide Dose Regimens When Used in Combination With Low Dose Dexamethasone for the Treatment of Subjects With Relapsed Multiple Myeloma
This is a research study to evaluate two different Lenalidomide doses (15 mg vs. 25 mg) in
combination with low dose dexamethasone in patients with relapsed multiple myeloma.
The investigators propose to use the need for dose reduction as a criterion to judge
tolerability from various causes. In the veteran population which predominantly is in the
older age category with number of co-morbidities, a lower dose regimen may be safer and
advantageous.
This study expects to enroll approximately 80 subjects from participating VA sites across
the nation.
The investigators will evaluate the safety of the two dose regimens by comparing frequency
of dose reductions. The investigators will also measure how long the responses last with
each dose.
Lenalidomide is approved by the Food and Drug Administration (FDA) for the treatment of
specific types of myelodysplastic syndrome (MDS) and in combination with dexamethasone for
patients with multiple myeloma (MM) who have received at least 1 prior therapy. MDS and MM
are cancers of the blood. It is currently being tested in a variety of cancer conditions. In
this case it is considered experimental.
At the time of enrollment, one-half of the subjects will be chosen at random to receive the
15 mg Lenalidomide dose and the other half will take the 25 mg dose regimen of Lenalidomide.
Depending on lenalidomide treatment assignment, subjects will receive either 15 mg p.o. q.d.
or 25 mg p.o. q.d. for days 1-21 of a 28 day cycle. In addition, dexamethasone (40 mg) will
be added once a week (Days 1, 8, 15 and 22) to the Lenalidomide regimen, with a dose
reduction on the same schedule if the patient cannot tolerate the higher dose of
dexamethasone. ASA (81 or 325mg) will be given daily for anticoagulation prophylaxis.
Patients intolerant to ASA may use low molecular weight heparin. Lovenox is recommended.
Coumadin will be allowed provided the patient is fully anticoagulate with INR 2.0 to 2.5.
combination with low dose dexamethasone in patients with relapsed multiple myeloma.
The investigators propose to use the need for dose reduction as a criterion to judge
tolerability from various causes. In the veteran population which predominantly is in the
older age category with number of co-morbidities, a lower dose regimen may be safer and
advantageous.
This study expects to enroll approximately 80 subjects from participating VA sites across
the nation.
The investigators will evaluate the safety of the two dose regimens by comparing frequency
of dose reductions. The investigators will also measure how long the responses last with
each dose.
Lenalidomide is approved by the Food and Drug Administration (FDA) for the treatment of
specific types of myelodysplastic syndrome (MDS) and in combination with dexamethasone for
patients with multiple myeloma (MM) who have received at least 1 prior therapy. MDS and MM
are cancers of the blood. It is currently being tested in a variety of cancer conditions. In
this case it is considered experimental.
At the time of enrollment, one-half of the subjects will be chosen at random to receive the
15 mg Lenalidomide dose and the other half will take the 25 mg dose regimen of Lenalidomide.
Depending on lenalidomide treatment assignment, subjects will receive either 15 mg p.o. q.d.
or 25 mg p.o. q.d. for days 1-21 of a 28 day cycle. In addition, dexamethasone (40 mg) will
be added once a week (Days 1, 8, 15 and 22) to the Lenalidomide regimen, with a dose
reduction on the same schedule if the patient cannot tolerate the higher dose of
dexamethasone. ASA (81 or 325mg) will be given daily for anticoagulation prophylaxis.
Patients intolerant to ASA may use low molecular weight heparin. Lovenox is recommended.
Coumadin will be allowed provided the patient is fully anticoagulate with INR 2.0 to 2.5.
Primary Objective:
• Evaluate the frequency of dose reductions in two different lenalidomide dose regimens.
Secondary Objectives:
- Evaluate the efficacy of two different lenalidomide dose regimens in patients with
multiple myeloma using the EBMT and IMWG criteria.
- Evaluate the duration of response of 15 mg Lenalidomide and 25 mg of Lenalidomide when
used in combination with Low Dose Dexamethasone.
- Evaluate the safety of 15 mg and 25 mg of Lenalidomide regiments when in combination
with dexamethasone.
- Explore blood and cellular levels of angiogenic factors, cytokines, and adhesion
molecules.
• Evaluate the frequency of dose reductions in two different lenalidomide dose regimens.
Secondary Objectives:
- Evaluate the efficacy of two different lenalidomide dose regimens in patients with
multiple myeloma using the EBMT and IMWG criteria.
- Evaluate the duration of response of 15 mg Lenalidomide and 25 mg of Lenalidomide when
used in combination with Low Dose Dexamethasone.
- Evaluate the safety of 15 mg and 25 mg of Lenalidomide regiments when in combination
with dexamethasone.
- Explore blood and cellular levels of angiogenic factors, cytokines, and adhesion
molecules.
Inclusion Criteria:
1. Previously diagnosed with multiple myeloma.
2. Must have relapsed or refractory disease (refractory is defined as progression during
treatment or within 60 days after the completion of treatment) requiring 2nd or 3rd
line therapy
3. Patients may have received lenalidomide and/or dexamethasone
4. Patients must have measurable disease:
- Serum monoclonal protein >0.5g/dL and/or 0.2g/24hr urine light chain excretion
- Patients with lower M-protein values or non-secretory myeloma will be eligible
if measurable disease can be established, such as serum FreeliteTM chain ratio
>5x ULN, measurable soft tissue plasmacytoma >2cm by either physical exam and/or
applicable radiographs (i.e. MRI, CT-scan) and/or bone marrow involvement >30%
5. Age >=18 years at the time of consent.
6. All necessary baseline studies for determining eligibility must be obtained within 14
days prior to enrollment. Serum pregnancy tests (sensitivity of at least 25 mIU/mL),
for females of childbearing potential (WCBP) must be completed. The first test must
be performed within 10-14 days, and the second test within 24 hours prior to
initiation of lenalidomide.
7. Pre-study ECOG performance status 0-2. Patients with lower performance status based
solely on bone pain will be eligible.
8. Adequate liver functions: AST and ALT =< 3xULN, alkaline phosphatase =< 3.0x ULN,
except if attributed to tumor, and bilirubin =< 2xULN.
9. Have Amylase =< 2.5x ULN
10. Able to adhere to the study visit schedule and other protocol requirements
11. Must understand and voluntarily sign an informed consent document.
12. Females of childbearing potential (FCBP)† must have a negative serum or urine
pregnancy test with a sensitivity of at least 50 mIU/mL 10 - 14 days prior to and
again within 24 hours of starting lenalidomide and must either commit to continued
abstinence from heterosexual intercourse or begin TWO acceptable methods of birth
control, one highly effective method and one additional effective method AT THE SAME
TIME, at least 4 weeks before she starts taking lenalidomide. FCBP must also agree to
ongoing pregnancy testing. Men must agree not to father a child and agree to use a
condom if his partner is of child bearing potential. All patients must be counseled
at a minimum of every 28 days about pregnancy precautions and risks of fetal
exposure.
13. All study participants must be registered into the mandatory RevAssist® program, and
be willing and able to comply with the requirements of RevAssist®. All counseling
will be done through RevAssist®.
14. Able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation. Patients
intolerant to ASA may use low molecular weight heparin. Lovenox is recommended.
Coumadin will be allowed provided the patient is fully anticoagulate with INR 2.0 to
2.5.
15. Patients may receive a bisphosphonate.
Exclusion Criteria:
1. Any serious medical condition, laboratory abnormality, or psychiatric illness that
would prevent the subject from signing the informed consent form.
2. Pregnant or breast feeding females.(Lactating females must agree not to breast feed
while taking lenalidomide).
3. Any condition, including the presence of laboratory abnormalities, which places the
subject at unacceptable risk if he/she were to participate in the study or confounds
the ability to interpret data from the study.
4. Renal insufficiency of creatinine clearance <40mL/min
5. Known hypersensitivity to thalidomide or lenalidomide.
6. Development of erythema nodosum if characterized by a desquamating rash while taking
thalidomide or similar drugs.
7. Concurrent use of other anti-cancer agents or treatments.
8. Known seropositive for an active viral infection with human immunodeficiency virus
(HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV). Patients who are
seropositive because of hepatitis B virus vaccine are eligible.
9. Has hemoglobin <8.0g/dL. The use of transfusion with pRBC to correct anemia and meet
eligibility criteria will not be allowed.
10. Has an absolute neutrophil count <1.0x10^9/L within 14 days before enrollment
11. Peripheral neuropathy of grade >=3. Patients with painful grade 2 neuropathy are also
excluded
12. Has platelet count <75x10^9/L within 14 days before enrollment.
13. Plasma cell leukemia at time of study entry.
We found this trial at
7
sites
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