Treatment of MDS patients with single agent temsirolimus – a pilot study

Active, not recruiting

• Conditions: Myelodysplastic Syndromes (MDS)(20 IPSS LOW+INT-1 and 20 IPSS INT-2+HIGH or proliferating CMML); MedDRA version: 14.1Level: PTClassification code 10028533Term: Myelodysplastic syndromeSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2009-014768-21-DE
• Lead Sponsor: Dresden Technical University

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2010-01-05
• Last Update Posted: 11 August 2014

Recruitment & Eligibility

• Status: Not Recruiting
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

1. Age greater/equal 18 years at the time of signing the informed consent form;

2. 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 study entry 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.

3. Not eligible for an immediate allogeneic HSCT or conventional chemotherapy

4. All previous MDS specific therapies (except supportive approaches like transfusions or antibiotics) must have been discontinued at least 4 weeks prior to study enrollment.

5. ECOG performance status of <=3 at study entry (see Appendix 01).

6. 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

7. signed informed consent.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 40
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. 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);

2. 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);

3. known hypersensitivity to macrolid antibiotics (because of structural similarities between this class of antibiotics and study medication);

4. 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;

5. known positive for HIV or any other uncontrolled infection;

6. 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);

7. necessity of therapeutic anticoagulation (excluding low dose ASS);

8. participation in an other clinical trial within the last 4 weeks;

9. pregnant or breastfeeding females (lactating females must agree not to breast feed while on study);

10. females of childbearing potential (FCBP) except those fulfilling 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);

11. 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;

12. 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;

13. patients who are not likely to follow the trial protocol (lack of willigness to cooperate).

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: Evaluate the response of MDS patients to temsirolimus<br>;Secondary Objective: - Toxicity as measured by NCI CTCAE v3.0<br>- Overall survival at 1 year<br>- Progression-free-survival at 1 year<br>- Rate of leukemic progression at 1 year <br>- Overall hematological response rate at 1 year using modified IWG-criteria<br>- Quality of life as measured by EORTC-QLQ30<br>;Primary end point(s): Primary endpoint is the overall hematological response rate (combination of CR, PR, marrow-CR and SD with HI) at 4 months using modified IWG-criteria<br><br>;Timepoint(s) of evaluation of this end point: 1 . After 4 or 12 months of treatment

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Secondary Endpoints<br>•Toxicity as measured by NCI CTCAE v3.0;<br>•overall survival at 1 year;<br>•progression-free survival at 1 year;<br>•rate of leukemic progression at 1 year;<br>•overall hematological response rate at 1 year using modified IWG-criteria;<br>•quality of life as measured by EORTC-QLQ30.<br>;Timepoint(s) of evaluation of this end point: every visit