E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Low And Intermediate-1 Risk Myelodysplastic Syndrome in adult patients 60 years or younger |
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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.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of this study is to determine the Hematologic Improvement (HI) rate during the 12-month study period with rATG (Thymoglobulin), as defined by the IWG and published in 2006 by Cheson and colleagues |
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E.2.2 | Secondary objectives of the trial |
•To determine the duration of HI. •To determine the disease remission (Complete Remission (CR) +Partial Remission (PR))rate. •To determine the duration of disease remission (CR + PR). •To determine the Transfusion Independence (TI) rate. •To determine the duration of TI. •To determine the relapse rate after HI, CR, or PR. •To determine the cytogenetic response and marrow CR rates. •To determine progression free survival. •To determine the rate of transformation to Acute Myeloid Leukemia (AML)
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Provides signed written informed consent.
2.Has pathologically confirmed MDS with a low or intermediate-1 risk score as assessed by IPSS at the time of MDS diagnosis.
3.Has received no more than 1 prior treatment for MDS (excluding supportive care such as transfusions and antibiotics), which is restricted to the following treatments that may have been administered as a standard treatment or as an investigational agent. Treatment with any of these agents must have been discontinued at least 4 weeks before Day 1 of the study treatment. •Hematopoietic growth factors: EPO or any EPO derivative with or without concurrent granulocyte colony stimulating factor (G CSF) and/or granulocyte-macrophage colony stimulating factor GM-CSF) (For patients where EPO is an available therapy (country specific), the Investigator must determine that the patient either demonstrated a lack of response to EPO or did not meet the criteria predictive for an intermediate or high response as defined by the predictive model.) or •Prior treatment is restricted to azacitidine, decitabine, lenalidomide, or thalidomide.
4.Exhibited at least 1 of the following hematologic cytopenias as determined from at least 2 time points over at least a 1-week period. •Anemia (hemoglobin <11 g/dL) •Neutropenia (ANC <0.5 x 10*9 /L) •Thrombocytopenia (platelets <20 x10*9 /L).
5.Have documentation of prior transfusion requirements for the preceding 8 weeks and total duration of any ongoing RBC transfusion dependence.
6.Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
7.Be ≥18 and ≤60 years of age at the time of signing the informed consent document (ICD).
8.Is able to adhere to study visit schedule and all other protocol requirements.
9.Is willing to practice a medically approved method of birth control during participation in the study (at least 12 months after the last infusion of rATG) (fertile male and female patients).
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E.4 | Principal exclusion criteria |
1.Is pregnant or lactating.
2.Has had prior treatment with any ATG, cyclosporin, or any other immunomodulatory or immunosuppressing agent.
3.Has had a prior HSCT and/or other organ transplant.
4.Has had a prior allergic reaction to rabbit proteins or excipients.
5.Has 1 of the following subtypes of MDS: •refractory anemia with ringed sideroblasts (RARS), according to WHO classification, or •chronic myelomonocytic leukemia CMML (FAB) or CMML-1 and CMML-2 (WHO) if WBC count >13 x 10*9 /L, or •other MDS types of the MDS/myeloproliferative diseases (MPD) group according to WHO classification.
6.Has MDS associated with a 5q chromosomal deletion based upon local bone marrow cytogenetic analysis, unless the patient received prior lenalidomide treatment.
7.Has MDS presumed secondary to exposure to chemicals or treatment with radiotherapy or chemotherapy.
8.Received any treatment with an investigational agent, except the accepted previous treatments, within 4 weeks prior to the first infusion of rATG.
9.Has a blast count >10% at screening.
10.Has a serum creatinine >1.5 x upper limit of normal (ULN).
11.Received any treatment with non-steroidal anti-inflammatory drugs (NSAID) within 14 days prior to start of study treatment.
12.Has aspartate transaminase (AST) and alanine transaminase (ALT) >2.5 x ULN.
13.Has serum total bilirubin >1.5 ULN except for unconjugated hyperbilirubinemia related to the patient’s MDS.
14.Is known to be human immunodeficiency virus (HIV) positive.
15.Has any prior diagnosis of malignancy other than MDS, unless the patient has been disease-free for at least 5 years following the completion of curative intent therapy with the following exceptions: •Patients with treated basal-cell skin cancer, in situ carcinoma, or cervical intraepithelial neoplasia, regardless of the disease-free duration, are eligible for this study if definitive treatment for the condition has been completed, •Patients with organ-confined prostate cancer, with no evidence of recurrent or progressive disease based on prostate-specific antigen (PSA) values, are also eligible for this study, if hormonal therapy has been initiated or a radical prostatectomy has been performed.
16.Any history of an immune-related hematological disorder (eg, autoimmune idiopathic thrombocytopenia purpura [ITP]).
17.Any serious medical condition (other than MDS) that would limit survival to 2 years.
18.Active acute or chronic infection, and/or active cytomegaloviremia (CMV) infection with positive immunoglobulin M (IgM) titers, or latent deep tissue infection.
19.Any other serious medical condition, uncontrolled illness (including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia), social condition, or psychiatric illness that will prevent the patient from signing the ICD, or will place the patient at unacceptable risk if he/she participates in the study, or that would limit compliance with study requirements.
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E.5 End points |
E.5.1 | Primary end point(s) |
Hematologic improvement as assessed by the Investigator according to IWG guidelines |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
E.6.2 | Prophylaxis | Information not present in EudraCT |
E.6.3 | Therapy | No |
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 | Yes |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 8 |
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 | 4 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 3 |