E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
High risk Myelodysplastic Syndrome (IPSS Int-2 or High) or Acute Myeloid Leukemia with a karyotype including del(5q) or monosomy 5 |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10028533 |
E.1.2 | Term | Myelodysplastic syndrome |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10000886 |
E.1.2 | Term | Acute myeloid leukemia |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To study the efficacy of lenalidomide in high-risk MDS (IPSS Int-2 or high) and AML with a karyotype including del(5q) or monosomy 5 |
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E.2.2 | Secondary objectives of the trial |
To study the safety of increasing doses of lenalidomide in high-risk MDS (IPSS Int-2 or high) and AML with a karyotype including del(5q) or monosomy 5 |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Must be > or =18 years of age at the time of signing the informed consent form • MDS at IPSS Int-2 or High with a karyotype including del(5q) or monosomy 5 confirmed with FISH (using the LSI EGR1/D5S23,D5S721 FISH probe) • Acute myeloid leukemia with a karyotype including del(5q) or monosomy 5 confirmed with FISH (using the LSI EGR1/D5S23,D5S721 FISH probe) • Patients could be included if 1. At diagnosis and not considered eligible for induction chemotherapy 2. Refractory to induction therapy 3. Relapse after induction chemotherapy leading to CR and considered not eligible for reinduction 4. Relapse after allogeneic stem cell transplantation and not considered suitable for reinduction chemotherapy or other conventional relapse therapy. • Subject has signed the informed consent document. • Women of childbearing potential, WCBP, (A woman 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) must agree to practice complete abstinence from heterosexual intercourse or to use two methods of contraception beginning 4 weeks prior to the start of the study medication, while on study medication and 4 weeks after the last dose of study medication. The two methods of contraception must include one highly effective method (i.e. intrauterine device, hormonal birth control pills, injections, patches or implants, tubal ligation, partner’s vasectomy) and one additional effective (barrier) method (i.e. latex condom, diaphragm, cervical cap). However, the doctor may recommend that the subject use two barrier methods for medical reasons. The subject must talk to the doctor before changing any birth control methods she has already agreed to use. WCBP must have two negative serum or urine pregnancy tests (sensitivity of at least 50 mIU/mL) prior to starting study drug. The first pregnancy test must be performed within 10-14 days prior to the start of study drug and the second pregnancy test must be performed within 24 hours of starting study medication. The subject may not receive study drug until the investigator has verified that the results of these pregnancy test are negative. WCBP must agree to have pregnancy tests weekly for the first 4 weeks and then every 4 weeks while on study medication (in woman with regular cycles and every 2 weeks in women with irregular cycles, or earlier in the event the patient discontinues early) and 4 weeks after the last dose of study medication (In women with irregular cycles 2 and 4 weeks after the last dose of study medication). WCBP will be warned that sharing study drug is prohibited and will be counseled about pregnancy precautions and potential risks of fetal exposure before starting study drug and every 4 weeks during study treatment. • Males (including those who have had a vasectomy) must use barrier contraception (latex condoms) when engaging in reproductive sexual activity with WCBP while on study medication and 4 weeks after the last dose of study medication. Male subjects will also be warned that sharing study drug is prohibited and will be counseled about pregnancy precautions and potential risks of fetal exposure before starting study drug and every 4 weeks during study treatment.
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E.4 | Principal exclusion criteria |
• Pregnant or lactating females. • Prior therapy with lenalidomide • Patients who are eligible for curative treatment • Expected survival less than two months. • Acute promyelocytic leukemia (APL) • Absolute peripheral blast count >30,000/mm3 (see section 7.1 about the use of hydroxyurea) • Central nervous system leukemia • Serum biochemical values as follows 1. Serum creatinine >2.0 mg/dL (177 mmol/L) 2. Serum aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT) or alanine transaminase (ALT)/serum glutamate pyruvate transaminase (SGPT) >3.0 x upper limit of normal (ULN) 3. Serum total bilirubin >1.5 mg/dL (26 micromol/L) • Prior allergic reaction to thalidomide • Uncontrolled systemic infection
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E.5 End points |
E.5.1 | Primary end point(s) |
Major cytogenetic response (50% or more reduction of the del5(q) or monosomy 5 FISH positive clone in the bone marrow using the LSI EGR1/D5S23,D5S721 FISH probe, see section 8.3) after 16 weeks of lenalidomide treatment |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 17 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |