The goal of this clinical research study is to learn if Revlimid® (lenalidomide), along with
standard-of-care steroid treatment you are already receiving, can help to control cGVHD. The
safety of this study drug in combination with the steroids will also be studied.
- To assess the response rate of chronic GVHD to Lenalidomide after failing steroids
- To evaluate the safety and tolerability of Lenalidomide in patients with chronic GVHD
- To assess the steroid-sparing capacity of Lenalidomide (as proportion of patients able
to discontinue steroids while receiving or following therapy with Lenalidomide)
- To assess changes in QOL after treatment with Lenalidomide
- To analyze survival at 6 and 12 months after initiation of Lenalidomide
- To evaluate relapse of underlying malignancy as well as second malignancies at 6 and 12
months after initiation of Lenalidomide
Standard Care Treatment:
You are currently receiving steroids (corticosteroids, prednisone, or medrol), which is the
standard treatment for cGVHD.
Not all patients have a complete response to this steroid treatment, and long-term treatment
with steroids may cause cataracts, extreme muscle weakness, osteoporosis (bone disease),
diabetes, and/or fluid retention.
However, stopping steroid treatment may worsen the cGVHD.
The Study Drug:
Lenalidomide is designed to change the body's immune system. It may also interfere with the
development of tiny blood vessels that help support tumor growth. It may decrease or
prevent the growth of cancer cells.
Researchers want to find out if lenalidomide can improve the cGVHD and if it can help
decrease the amount of steroids you need, which may help prevent long-term side effects that
occur when steroids are used over a long period of time.
Before you can start treatment on this study, you will have "screening tests." These tests
will help the study doctor decide if you are eligible to take part in this study.
- Your study doctor will review any treatments you had for the cancer.
- You will be asked about any medications you may have taken within 4 weeks before
starting this study.
- You will have a complete physical exam, including measurement of your vital signs
(blood pressure, heart rate, breathing rate, and temperature), height, and weight.
- You will have an electrocardiogram (ECG -- a test that measures the electrical activity
of the heart).
- You will have the status of the cGVHD checked. For this assessment, you will complete
questionnaires so that the study doctor can find out how cGVHD impacts your quality of
life. It should take about 20 minutes to complete.
- You will have up to 2 tablespoons of blood drawn and urine collected for routine tests.
- You will have a chest x-ray.
Females who are able to have children will need to have 2 negative pregnancy tests, one test
will be 10-14 days before receiving the first dose of lenalidomide, another test will be
performed within the 24 hours before receiving the first dose of lenalidomide.
If you are found to be eligible to take part in this study, you will take lenalidomide by
mouth (1 larger-dose capsule or 2 smaller-dose capsules) once daily for 21 days followed by
7 days without treatment (a "rest period"). Each 28-day period is called a cycle of therapy.
You will have up to 6 cycles of therapy on this study.
Study Drug Administration:
You will swallow lenalidomide capsules whole with water (about 16 ounces) at the same time
each day. You should not break, chew, or open capsules. If you miss a dose of
lenalidomide, you should take it as soon as you remember on the same day. If you miss
taking your dose for the entire day, you will take your regular dose the next day ( DO NOT
take double your regular dose to make up for the missed dose).
During treatment, you will have additional testing to check for side effects and to learn
your body's response to therapy. You will have these tests every 2 weeks (during Cycles 1
and 2), once a month (during Cycles 3-6), and every 3 months for up to 1 year from when you
started treatment with the study drug.
- You will have a physical exam.
- You will have a full skin assessment. For this assessment, the study doctor will look
at your skin to see if your skin shows a reaction to the cGVHD transplant.
- You will have a 2-minute walking test. For this test, you will be asked to walk for 2
minutes, and your walking distance will be measured.
- You will have a grip strength test. For this test, you will be asked to sit down and
squeeze something that has a meter to measure your strength.
- You will complete some questionnaires about how you are feeling physically,
emotionally, and socially. It should take about 20 minutes to complete.
- You will complete another questionnaire about how you assess your symptoms. It should
take about 20 minutes to complete.
- You will have blood drawn (about 2 tablespoons) for routine tests and to check
immune-suppressive drug (such as tacrolimus or cyclosporine) levels in your blood.
- You will be asked about how you are feeling and about any side effects you may have
experienced since your last visit.
Females who are able to have children that have regular or no menstrual cycles must agree to
have pregnancy tests weekly for the first 28 days of study participation and then every 28
days while on study, at the end of the study, and 28 days following the end of the study.
If your menstrual cycles are irregular, the pregnancy testing must occur weekly for the
first 28 days and then every 14 days while on study, at study discontinuation, and at days
14 and 28 following discontinuation from the study.
Your dose of the study drug will be temporarily stopped or decreased if the study doctor
thinks it is necessary for your safety. Other drugs may also be given to you to help
decrease side effects. The study doctor will tell you what these drugs will be if this is
Length of Study:
You will be taken off this study if the disease gets worse or you experience any intolerable
side effects. If you are tolerating and responding to the study treatment, you will be on
this study for up to 1 year from enrollment.
This is an investigational study. Lenalidomide is FDA approved and commercially available
for the treatment of specific types of myelodysplastic syndrome (MDS). It is also approved
in combination with dexamethasone for previously treated multiple myeloma. Its use in this
study is investigational and authorized for use in research only. Up to 46 patients will
take part in this study. All will be enrolled at M. D. Anderson.
1. Patients with chronic GVHD following allogeneic HSCT of any source (bone marrow,
peripheral blood or cord blood stem cells), from any donor type (related, unrelated,
mismatched) and with any type of malignancy.
2. Patients must have failed a trial of steroids and calcineurin inhibitors. Steroids
must have been given at an initial dose of 1 mg/kg/d of methylprednisolone (MP) or
equivalent in combination with tacrolimus or cyclosporine. Steroid refractoriness or
resistance will be defined as: 1- Lack of any response after 1 month of treatment
with MP, including 15 days of at least 0.5 mg/kg/d, 2- Worsening of existing GVHD or
new organ involvement at any time following one week of initiation of MP at 1
mg/kg/day, 3- Reflare or worsening of GVHD at any time during steroid taper.
3. Patients may have received steroids and calcineurin inhibitors (i.e. cyclosporine or
tacrolimus) for chronic GVHD. Patients who have previously been treated for chronic
GVHD with any other drug or treatment may be enrolled, provided the other drug or
treatment was completed >/= 30 days before registration for study entry.
4. ECOG performance status </= 2.
5. WBC >/= 2,500/mm^3, ANC >/= 1,000/mm^3, platelet count >/= 50,000/mm^3
6. Left ventricular ejection fraction >/= 40%. No uncontrolled arrythmias or symptomatic
heart disease. FEV1, FVC and DLCO >/= 40%.
7. Serum creatinine <2.0 mg/dL. Serum bilirubin <3 X upper limit of normal, AST (SGOT)
and ALT (SGPT) < or = 5 x ULN. No evidence of chronic active hepatitis or cirrhosis.
8. No uncontrolled infections.
9. No evidence of malignancy (patients must be in complete remission from their
10. Patients must be able to provide written informed consent, and be 18 years or older
at the time of signing consent.
11. Patient must be able to return to clinic for follow up at least every 2 weeks for the
first 2 months and at least monthly thereafter.
12. Women of childbearing potential must have a negative serum or urine pregnancy test
with a sensitivity of at least 50 mIU/mL 10 - 14 days prior to therapy and repeated
within 24 hours of starting study drug and must either commit to continued abstinence
from heterosexual intercourse or agree to use 2 contraceptive methods. These birth
control methods must be used for at least 4 weeks before, during and after
lenalidomide therapy. Men must agree not to father a child and agrees to use a condom
if his partner is of child bearing potential.
13. Able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation. (patients
intolerant to ASA may use low molecular weight heparin).
1. Any serious medical condition, laboratory abnormality, or psychiatric illness that
would prevent the subject from signing the informed consent form.
2. Pregnant or lactating females.
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. Use of any other experimental drug or therapy within 28 days of baseline.
5. Known hypersensitivity to thalidomide.
6. The development of erythema nodosum if characterized by a desquamating rash while
taking thalidomide or similar drugs.
7. Any prior use of Lenalidomide.
8. Use of prior immunosuppressants other than steroids and calcineurin inhibitors (i.e.
cyclosporine or tacrolimus).
9. Known positive for HIV or infectious hepatitis, type A, B or C