Temsirolimus in Myelodysplastic Syndrome (MDS) (TEMDS)

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2012 by Technische Universität Dresden
Sponsor:
Collaborator:
Wyeth is now a wholly owned subsidiary of Pfizer
Information provided by (Responsible Party):
Technische Universität Dresden
ClinicalTrials.gov Identifier:
NCT01111448
First received: April 23, 2010
Last updated: December 18, 2012
Last verified: December 2012
  Purpose

The goal of this Pilot-study is to evaluate the response of unselected MDS patients to temsirolimus a drug approved for the treatment of renal cell cancer. It is planned to give temsirolimus at a weekly dose of 25 mg as intravenous infusion for a maximum duration of 12 months. Regular bone marrow biopsies are planned for controlling MDS response.


Condition Intervention Phase
Myelodysplastic Syndrome
Drug: Temsirolimus
Phase 0

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Treatment of MDS Patients With Single Agent Temsirolimus - a Pilot Study

Resource links provided by NLM:


Further study details as provided by Technische Universität Dresden:

Primary Outcome Measures:
  • Overall hematological response rate using modified IWG criteria (combination of CR, PR, marrow-CR and SD with HI). [ Time Frame: at 4 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Toxicity as measured by NCI CTCAE v3.0 [ Time Frame: 4 and 12 months ] [ Designated as safety issue: Yes ]
  • Overall survival [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Progression-free-survival [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Rate of leukemic progression [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Overall hematological response rate using modified IWG-criteria [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Quality of life as measured by EORTC-QLQ30 [ Time Frame: 4 months, 12 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 40
Study Start Date: April 2010
Estimated Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Temsirolimus
25 mg/day 1; 8; 15; 22 of each 28-day cycle
Drug: Temsirolimus
25 mg/day 1; 8; 15; 22 of each 28-day cycle as intravenous infusion over 30 min

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age >18 years at the time of signing the informed consent form;
  • Patients able to understand the consequences of participating in this trial and not having any disorders or other circumstances (i.e. being in ward or imprisoned) which keeps them from giving written informed consent;
  • cytologically or histologically established diagnosis of de novo or therapy-related MDS according to the FAB-classification, either previously treated or untreated, presenting with:

    • Group I (low-risk): Low- or INT-1 risk features according to IPSS and requiring at least 4 units of red blood cells within the last 8 weeks prior to screening visit or presenting with neutropenia (<1 Gpt/l neutrophils) or
    • Group II (high-risk): INT-2 or HIGH-risk IPSS refractory or intolerant to 5-Azacytidine.

CMML patients of dysplastic phenotype (WBC < 13 Gpt/l) may be included in both arms according to IPSS. CMML patients showing proliferative phenotype (WBC >=13 Gpt/l) will be included in the high risk arm;

  • not eligible for an immediate allogeneic HSCT or conventional chemotherapy;
  • all previous MDS specific therapies (except supportive approaches like transfusions or antibiotics) must have been discontinued at least 4 weeks prior to study enrollment;
  • ECOG performance status of <= 3 at study entry;
  • laboratory test results within these ranges:

    • Serum creatinine <= 177 µmo/l (<= 2.0 mg/dL);
    • total bilirubin <= 3 x ULN;
    • AST (SGOT) and ALT (SGPT) <= 3 x ULN;
    • total fasting cholesterol <= 9.1 mmol/l (350 mg/dl);
    • fasting triglyceride level <= 4.5 mmol/l (400 mg/dl);
    • platelets > 25 Gpt/l without transfusion support in patients with LOW- and INT-1 Risk according to IPSS;
  • signed informed consent.

Exclusion Criteria:

  • For Patients with LOW- or INT1-Risk according to IPSS: Thrombocytopenia below 25 Gpt/l (INT2- and HIGH-IPSS patients may be included irrespective of platelet count);
  • known hypersensitivity to temsirolimus, sirolimus or any components of the infusion solution (dl-alpha-tocopherol, propylene glycol, anhydrous citric acid, polysorbate 80, polyethylene glycol 400, dehydrated alcohol);
  • known hypersensitivity to macrolid antibiotics (because of structural similarities between this class of antibiotics and study medication);
  • 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;
  • known positive for HIV or any other uncontrolled infection;
  • presence of any other malignancy being not in complete remission for at least 3 years (previous chemotherapy for other malignancies is not an exclusion criteria);
  • necessity of therapeutic anticoagulation (excluding low dose ASS);
  • participation in an other clinical trial within the last 4 weeks;
  • pregnant or breast feeding females (lactating females must agree not to breast feed while on study);
  • females of childbearing potential (FCBP) except those fulfilling at least one of the following criteria:

    • post-menopausal (12 months of natural amenorrhea or 6 months of amenorrhea with serum FSH > 40 U/ml);
    • post-surgery (6 weeks after bilateral ovarectomy with or without hysterectomy);regular and correct use of contraceptives with a PEARL Index of < 1% (e.g. implants, depot formulations of hormones, oral contraceptives, intra uterine device - IUD);
    • sexual abstinence;
    • partner, who had vasectomy (confirmed by two negative analyses of semen);
  • male patients, who do not agree to use a latex condom during sexual contact with females of childbearing potential while participating in the study and for at least 3 months following discontinuation from the study even if he has undergone a successful vasectomy;
  • patients with a history of chronic drug abuse or another illness which does not allow the patient to assess the nature and/or possible consequences of the study;
  • patients who are not likely to follow the trial protocol (lack of willingness to cooperate).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01111448

Contacts
Contact: Uwe Platzbecker, MD, PhD +493514582583 uwe.platzbecker@uniklinikum-dresden.de
Contact: Martin Wermke, MD +493514582583 martin.wermke@uniklinikum-dresden.de

Locations
Germany
Klinikum Chemnitz Klinik für Innere Medizin III Recruiting
Chemnitz, Germany, 09113
Contact: Matthias Hänel, MD, PhD    +49371 333-43045      
Universitätsklinikum C. G. Carus der TU Dresden Recruiting
Dresden, Germany, 01307
Contact: Uwe Platzbecker, MD, PhD    +493514582583    uwe.platzbecker@uniklinikum-dresden.de   
Contact: Martin Wermke, MD    +493514582583    martin.wermke@uniklinikum-dresden.de   
Principal Investigator: Uwe Platzbecker, MD, PhD         
Sub-Investigator: Martin Wermke, MD         
Universitätsklinikum Düsseldorf Klinik für Hämatologie, Onkologie und Klin. Immunologie Not yet recruiting
Düsseldorf, Germany, 40225
Contact: Andrea Kuendgen, MD, PhD    +4921181 17720      
Universitätsmedizin Göttingen Georg-August-Universität Abteilung Hämatologie und Onkologie Recruiting
Goettingen, Germany, 37075
Contact: Detlef Haase, MD, PhD    +49 551 39-8891      
Forschungsgesellschaft mbH Recruiting
Leipzig, Germany, 04289
Contact: Ali Aldaoud, MD    +493419616126      
Universitätsklinikum Leipzig AöR Recruiting
Leipzig, Germany, 04103
Contact: Haifa-Katrin Al-Ali, MD    +4934197 13132      
Klinikum Mannheim GmbH III. Medizinische Universitätsklinik -SP Hämatologie/Onkologie Not yet recruiting
Mannheim, Germany, 68167
Contact: Wolf-Karsten Hofmann, MD, PhD    +49621383 4115      
Sponsors and Collaborators
Technische Universität Dresden
Wyeth is now a wholly owned subsidiary of Pfizer
Investigators
Principal Investigator: Uwe Platzbecker, MD, PhD Medizinische Klinik I, Universitätsklinikum Carl-Gustav-Carus, Dresden, Germany
  More Information

No publications provided

Responsible Party: Technische Universität Dresden
ClinicalTrials.gov Identifier: NCT01111448     History of Changes
Other Study ID Numbers: TUD-TEMDS1-042
Study First Received: April 23, 2010
Last Updated: December 18, 2012
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Technische Universität Dresden:
Myelodysplastic Syndromes of all IPSS subgroups

Additional relevant MeSH terms:
Myelodysplastic Syndromes
Preleukemia
Syndrome
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Neoplasms
Disease
Pathologic Processes
Sirolimus
Everolimus
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 18, 2014