Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Dose Range Finding Study of Lenalidomide in Non-5q Chromosome Deletion in Low and Intermediate Risk Myelodysplastic Syndrome (MDS) Patients

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00699842
Recruitment Status : Terminated (Administratively terminated per FDA recommendation)
First Posted : June 18, 2008
Results First Posted : June 3, 2014
Last Update Posted : November 29, 2016
Sponsor:
Collaborator:
Celgene Corporation
Information provided by (Responsible Party):
Thomas Jefferson University ( Sidney Kimmel Cancer Center at Thomas Jefferson University )

Tracking Information
First Submitted Date  ICMJE June 13, 2008
First Posted Date  ICMJE June 18, 2008
Results First Submitted Date  ICMJE February 27, 2014
Results First Posted Date  ICMJE June 3, 2014
Last Update Posted Date November 29, 2016
Study Start Date  ICMJE July 2008
Actual Primary Completion Date January 2011   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 14, 2011)
Determine CR, PR, and Rate of Stable Disease in MDS Patients [ Time Frame: 2 years ]
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
Original Primary Outcome Measures  ICMJE
 (submitted: June 17, 2008)
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 [ Time Frame: 2 years ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 14, 2011)
Safety With Dose Escalation [ Time Frame: 2 years ]
Safety (type, frequency, severity, and relationship of adverse events to study treatment) with dose escalation.
Original Secondary Outcome Measures  ICMJE
 (submitted: June 17, 2008)
Safety (type, frequency, severity, and relationship of adverse events to study treatment) with dose escalation. [ Time Frame: 2 years ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Dose Range Finding Study of Lenalidomide in Non-5q Chromosome Deletion in Low and Intermediate Risk Myelodysplastic Syndrome (MDS) Patients
Official Title  ICMJE A Phase I/II Optimal Dose Study of Lenalidomide in the Non-5q- LOW and INT-1 Risk MDS Patients
Brief Summary Revlimid® (Lenalidomide) is indicated for a type of blood cancer, myelodysplastic syndrome (MDS), at 10mg for a specific type of myelodysplastic syndrome with a genetic abnormality called "deletion 5q" in Low and Intermediate-1 (INT-1) patients (staging system according to International Prognostic Scoring System (IPSS)). The purpose of this Phase I/II study is to determine the optimal dose of Revlimid® (Lenalidomide) in MDS Low and MDS INT-1 patients without deletion 5q by slowly increasing the dose while monitoring blood counts for safety evaluation as well as observe other adverse events. Efficacy will also be observed for the phase II portion of the study.
Detailed Description

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Myelodysplastic Syndrome
  • MDS
  • Low to Intermediate-1 MDS
  • Non-deletion 5q
Intervention  ICMJE Drug: Lenalidomide

Dose Level Lenalidomide Schedule

  1. 15mg/day for d1-21 out of 28 days
  2. 20mg/day for d1-21 out of 28 days
  3. 25mg/day for d1-21 out of 28 days
Other Name: Revlimid
Study Arms  ICMJE Experimental: Lenalidomide
Lenalidomide will be given orally on day 1-21, followed by a 7day rest (28 day cycle). Cycles will be repeated every 28 days.
Intervention: Drug: Lenalidomide
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: January 3, 2012)
8
Original Estimated Enrollment  ICMJE
 (submitted: June 17, 2008)
25
Actual Study Completion Date  ICMJE May 2012
Actual Primary Completion Date January 2011   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 study.
  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 present.
  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 anticoagulation

    -

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00699842
Other Study ID Numbers  ICMJE 07C.446
RV-MDS-PI-244 ( Other Identifier: Celgene )
2007-31 ( Other Identifier: CCRRC )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Thomas Jefferson University ( Sidney Kimmel Cancer Center at Thomas Jefferson University )
Study Sponsor  ICMJE Sidney Kimmel Cancer Center at Thomas Jefferson University
Collaborators  ICMJE Celgene Corporation
Investigators  ICMJE
Principal Investigator: Emmanuel Besa, MD Thomas Jefferson University
PRS Account Thomas Jefferson University
Verification Date October 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP