Safety of Lenalidomide and Markers for Disease Progression in Patients With International Prognostic Scoring System (IPSS) Low- or Intermediate-1 Risk Myelodysplastic Syndromes (MDS) With Isolated del5q (MDS-LE-MON-5)

This study has been completed.
Sponsor:
Collaborator:
ClinAssess GmbH
Information provided by (Responsible Party):
Gesellschaft fur Medizinische Innovation – Hamatologie und Onkologie mbH
ClinicalTrials.gov Identifier:
NCT01081431
First received: March 2, 2010
Last updated: March 11, 2013
Last verified: March 2013

March 2, 2010
March 11, 2013
March 2010
December 2012   (final data collection date for primary outcome measure)
To identify predictive factors for disease progression in patients with MDS and an isolated deletion del(5q), blast count <5%, undergoing treatment with lenalidomide [ Time Frame: maximum 4 years ] [ Designated as safety issue: No ]
To identify predictive factors for disease progression in patients with MDS and an isolated deletion del(5q), blast count <5%, undergoing treatment with lenalidomide [ Time Frame: 2 years ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01081431 on ClinicalTrials.gov Archive Site
  • Transfusion Independency on 56 consecutive days after enrollment [ Time Frame: maximum 4 years ] [ Designated as safety issue: No ]
  • Cytologic Review [ Time Frame: maximum 4 years ] [ Designated as safety issue: No ]
    Investigation of bone marrow to identify blasts, ringed sideroblasts and dysplastic changes
  • Transfusion Independency on 56 consecutive days after enrollment [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Cytologic Review [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Investigation of bone marrow to identify blasts, ringed sideroblasts and dysplastic changes
Not Provided
Not Provided
 
Safety of Lenalidomide and Markers for Disease Progression in Patients With International Prognostic Scoring System (IPSS) Low- or Intermediate-1 Risk Myelodysplastic Syndromes (MDS) With Isolated del5q
A Multicenter, Single-arm, Open-label Phase II Study of the Safety of Lenalidomide Monotherapy and Markers for Disease Progression in Patients With IPSS Low- or Intermediate-1 Risk Myelodysplastic Syndromes (MDS) Associated With an Isolated Deletion 5q Cytogenetic Abnormality (Del 5q)

The purpose of this study is to determine the safety of lenalidomide and markers for disease progression in the treatment of IPSS low- or intermediate-1 risk MDS with isolated del5q.

Lenalidomide has been successfully used in patients with MDS in several studies. A small proportion of patients with MDS and del(5q) developed leukemia while treated with Lenalidomide. Up to now it is unknown what patients are at risk to progress while being treated with Lenalidomid. Therefore it is planned to examine not only the traditional clinical parameters like disease status and proportion of blasts, but also cytogenetic findings, gene expression, antiangiogenic effect, marrow fibrosis, mesenchymal stem cell as well as mitochondrial DNA mutation at baseline and in the course of the study performed by central laboratories. Moreover, long-term data are required, e.g., with regard to the development of AML. Therefore, it is planned to collect data from all patients with MDS and del 5q (isolated, blast count <5%) in whom treatment with lenalidomide is the best therapeutic option according to the investigator's assessment in a structured fashion.

Interventional
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Myelodysplastic Syndromes
Drug: Lenalidomide
10 mg d1-d21 of a 28-day cycle
Other Names:
  • CC5013
  • CC-5013
  • Revlimid
Experimental: Lenalidomide
Intervention: Drug: Lenalidomide
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
91
December 2012
December 2012   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Must understand and voluntarily sign an informed consent form
  • Age ≥ 18 years at the time of signing the informed consent form.
  • Must be able to adhere to the study visit schedule and other protocol requirements
  • Cytologically/histologically confirmed diagnosis of MDS with del 5q (isolated, blast count <5%), IPSS low or intermediate-1.
  • Transfusion dependency with at least 1 concentrates of erythrocytes within 8 weeks prior to first administration of study drug.
  • Start of treatment with lenalidomide is the best therapeutic option for the patient according to the investigator's assessment There are - apart from individual cases with erythropoetin level lower than 500 U/l and allogeneic transplantation for younger patients - no authorized alternative treatment options. Chemotherapy with low dose cytosine arabinoside may result in hematologic improvement. However, concerning the risk-benefit-assessment this chemotherapy is more unfavorable than lenalidomide due to cytopenia and mutagenic effects.
  • Female subjects of childbearing potential must:

    • Understand that the study medication has a teratogenic risk
    • Agree to use, and be able to comply with, effective contraception without interruption, 4 weeks before starting study drug, throughout study drug therapy (including dose interruptions) and for 4 weeks after the end of study drug therapy, even if she has amenorrhoea. This applies unless the subject commits to absolute and continued abstinence confirmed on a monthly basis. The following are effective methods of contraception*: (Implant,Levonorgestrel-releasing intrauterine system (IUS)**,Medroxyprogesterone acetate depot, Tubal sterilisation, Sexual intercourse with a vasectomised male partner only; vasectomy must be confirmed by two negative semen analyses, Ovulation inhibitory progesterone-only pills (i.e., desogestrel))
    • Agree to have a medically supervised pregnancy test with a minimum sensitivity of 25 mIU/ml not more than 3 days before the start of study medication once the subject has been on effective contraception for at least 4 weeks. This requirement also applies to women of childbearing potential who practice complete and continued abstinence.
    • Agree to have a medically supervised pregnancy test every 4 weeks including 4 weeks after the end of study treatment, except in the case of confirmed tubal sterilization. These tests should be performed not more than 3 days before the start of next treatment. This requirement also applies to women of childbearing potential who practice complete and continued abstinence

(*) Combined oral contraceptive pills are not recommended. If a subject was using combined oral contraception, she must switch to one of the methods above. The increased risk of VTE continues for 4 to 6 weeks after stopping combined oral contraception.

(**) Prophylactic antibiotics should be considered at the time of insertion particularly in patients with neutropenia due to risk of infection

  • Male subjects must

    • Agree to use condoms throughout study drug therapy, during any dose interruption and for one week after cessation of study therapy if their partner is of childbearing potential and has no contraception.
    • Agree not to donate semen during study drug therapy and for one week after end of study drug therapy.
  • All subjects must

    • Agree to abstain from donating blood while taking study drug therapy and for one week following discontinuation of study drug therapy.
    • Agree not to share study medication with another person and to return all unused study drug to the investigator

Exclusion Criteria:

  • Pregnant or lactating females
  • IPSS intermediate-2 or high-risk
  • Proliferative (WBC ≥ 12 x 109/L) CMML
  • Any of the following laboratory abnormalities:

    • Absolute neutrophil count (ANC) < 1 x 109/L
    • Platelet count < 50 x 109/L
    • Serum aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT) or alanine transaminase (ALT)/serum glutamate pyruvate transaminase (SGPT) > 3.0 x upper limit of normal (ULN)
    • Serum total bilirubin > 1.5 mg/dL Degree of severity of anemia is no exclusion criteria due to intensive interindividual variations of the haemoglobin value at time of transfusion.
  • Prior ≥ grade-2 NCI CTCAE allergic reaction to thalidomide
  • Prior desquamating (blistering) rash while taking thalidomide
  • Neuropathy ≥ grade 2
  • Clinically significant anemia owing to iron, B12, or folate deficiencies, or autoimmune or hereditary hemolysis or gastrointestinal bleeding (the subject must have a marrow aspirate that is evaluable for storage iron)
  • Prior history of malignancy other than MDS (except basal cell or squamous cell carcinoma or carcinoma in situ of the cervix or breast) unless the subject has been free of disease for ≥ 3 years
  • Concomitant use of androgens (exception: treatment of hypogonadism)
  • Concomitant use of specific treatments for MDS
  • Known HIV-1 positivity
  • Participation in another clinical study in the 4 weeks prior to enrollment or during this study
  • Prior treatment with lenalidomide
  • Any serious medical condition or psychiatric illness that will prevent the subject from signing the informed consent form or will place the subject at unacceptable risk if he/she participates in the study.
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Germany
 
NCT01081431
RV-MDS-PI-409, 2008-001866-10, GMIHO-003/2008
Yes
Gesellschaft fur Medizinische Innovation – Hamatologie und Onkologie mbH
Gesellschaft fur Medizinische Innovation – Hamatologie und Onkologie mbH
ClinAssess GmbH
Principal Investigator: Ulrich Germing, Prof. Heinrich-Heine University, Duesseldorf
Gesellschaft fur Medizinische Innovation – Hamatologie und Onkologie mbH
March 2013

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