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A Phase I/II Optimal Dose Study of Lenalidomide in the Non-5q- LOW and INT-1 Risk MDS Patients

Phase 1/Phase 2
18 Years
Not Enrolling
Myelodysplastic Syndrome, MDS, Low to Intermediate-1 MDS, Non-deletion 5q

Thank you

Trial Information

A Phase I/II Optimal Dose Study of Lenalidomide in the Non-5q- LOW and INT-1 Risk MDS Patients

There are little options for non deletion 5q Low and INT-1 patients. This study aims to
find an early clinical signal for higher activity and better response with lenalidomide in
patients with non deletion 5q Low and INT-1 MDS patients. Lenalidomide is an
immunomodulatory agent. Thalidomide, the parent compound, has both immunomodulatory and
anti-angiogenic properties which could confer anti-tumor and anti-metastatic efforts.
Lenalidomide has been demonstrated to possess anti-angiogenic activity through inhibition of
basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF) and tumor
necrosis factor-alpha (TNF-alpha) induced endothelial cell migration (movement of cells in
preparation to form new abnormal blood vessels for cancer cells), due at least in part to
inhibition of Akt phosphorylation response to bFGF.

In addition, lenalidomide has a variety of immunomodulatory effects. Lenalidomide stimulates
T cell proliferation, and the production of interleukin-2 (IL-2), IL-10 and interferon-gamma
(IFN-gamma), inhibits IL-1 beta and IL-6 and modulated IL-12 production.

Although the exact anti-tumor mechanism of action of lenalidomide is unknown, a number of
mechanisms are postulated for the activity of Lenalidomide in MDS.

Inclusion Criteria:

1. Understand and voluntarily sign an informed consent form.

2. Age 18 years at the time of signing the informed consent form.

3. Able to adhere to the study visit schedule and other protocol requirements.

4. MDS patients who fulfill diagnostic criteria and classification by the IPSS Low or
Int-1 categories according to cytogenetics, blood cytopenias and bone marrow blasts.
See Appendix II.

5. All previous therapy such as azacitidine, decitabine, growth factors such as EPO
(Procrit or Aranesp) and (Neupogen or Neulasta, Leukine, Neumega) or experimental
therapy, must have been discontinued at least 4 weeks prior to treatment in this

6. ECOG performance status of 2 at study entry (see Appendix I).

7. Laboratory test results within these ranges:

- Absolute neutrophil count 500/mm3

- Platelet count 50,000 /mm3

- Serum creatinine 2.0 mg/dL

- Total bilirubin 1.5 mg/dL

- AST (SGOT) and ALT (SGPT) 2 x ULN or 5 x ULN if hepatic metastases are

8. Females of childbearing potential (FCBP) must have a negative serum or urine
pregnancy test with a sensitivity of at least 50 mIU/mL within 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 28 days before she starts taking lenalidomide. FCBP must also
agree to ongoing pregnancy testing. Men must agree to use a latex condom during
sexual contact with a FCBP even if they have had a successful vasectomy. All
patients must be counseled at a minimum of every 28 days about pregnancy precautions
and risks of fetal exposure. See Appendix V: Risks of Fetal Exposure, Pregnancy
Testing Guidelines and Acceptable Birth Control Methods, AND also Appendix VI:
Education and Counseling Guidance Document.

9. Disease free of prior malignancies for 5 years with exception of currently treated
basal cell, squamous cell carcinoma of the skin, or carcinoma "insitu" of the cervix
or breast

- A female of childbearing potential is a sexually mature woman who: 1) has not
undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally
postmenopausal for at least 24 consecutive months (i.e., has had menses at any
time in the preceding 24 consecutive months).

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. 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. Concurrent use of other anti-cancer agents or treatments.

9. Known positive for HIV or infectious hepatitis, type A, B or C.

10. Myocardial infarction within 6 months prior to enrollment, or New York Hospital
Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe
uncontrolled ventricular arrhythmias, electrocardiographic evidence of acute ischemia
or active conduction system abnormalities.

11. History of thromboembolic disease within the past 6 months, regardless of


Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Determine CR, PR, and rate of stable disease in MDS patients

Outcome Description:

Determine CR, PR, and rate of stable disease in MDS patients, IPSS Score LOW or INT-1 who do not have the 5q- cytogenetic abnormality according to the IWG criteria for response in >10mg doses of lenalidomide

Outcome Time Frame:

2 years

Safety Issue:


Principal Investigator

Emmanuel Besa, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Thomas Jefferson University


United States: Food and Drug Administration

Study ID:




Start Date:

July 2008

Completion Date:

July 2013

Related Keywords:

  • Myelodysplastic Syndrome
  • MDS
  • Low to Intermediate-1 MDS
  • Non-deletion 5q
  • Myelodysplastic Syndrome
  • MDS
  • Low to Intermediate-1 MDS
  • Non-deletion 5q
  • Lenalidomide
  • Chromosome Deletion
  • Myelodysplastic Syndromes
  • Preleukemia



Thomas Jefferson University Philadelphia, Pennsylvania  19107-6541
Associates in Hematology-Oncology, PC Chester, Pennsylvania  19130