E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Conditioning therapy before haploidentical hematopoietic stem cell transplantation |
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E.1.1.1 | Medical condition in easily understood language |
Preparative chemotherapy before blood or marrow stem cell transplantation |
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E.1.1.2 | Therapeutic area | Diseases [C] - Blood and lymphatic diseases [C15] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 22.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10059044 |
E.1.2 | Term | Allogeneic peripheral hematopoietic stem cell transplant |
E.1.2 | System Organ Class | 100000004865 |
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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 assess the efficacy and safety of TreoFC conditioning before haploidentical hematopoietic stem cell transplantation (HSCT) in older or comorbid patients. The primary endpoint is overall survival (OS) 1 year after haploidentical HSCT. |
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E.2.2 | Secondary objectives of the trial |
• To assess rates of non-relapse mortality (NRM), relapse-free survival (RFS), graft-versus-host disease (GVHD) and relapse-free survival (GRFS), acute GVHD, chronic GVHD, quality of life (QOL), toxicity, engraftment, and chimerism in the study population. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patients with acute myeloid leukemia (AML) according to WHO 2016 (AML in complete remission at transplant, i.e., blast counts <5% in bone marrow) or myelodysplastic syndrome according to WHO 2016 (MDS with blast counts <20 % in bone marrow during disease history) indicated for haploidentical HSCT but considered to be at increased risk for standard conditioning therapies according to the following criteria: • patients aged ≥50 years at transplant and/or • patients with an HCT-CI score >2 [according to Sorror et al., 2005] 2. Availability of a haploidentical (HLA match ≥5/10) first- or second-degree related donor. Donor selection is based on molecular high-resolution typing (4 digits) of class II alleles of the DRB1 and DQB1 gene loci and molecular (at least) low-resolution typing (2 digits) of class I alleles (i.e., antigens) of the HLA- A, B, and C gene loci. 3. Adult patients of both gender, age 18-70 years 4. Karnofsky Index ≥60 % 5. Written informed consent 6. Men capable of reproduction and women of childbearing potential must be willing to consent to use a highly effective method of birth control such as condoms, implants, injectables, combined oral contraceptives, IUDs, sexual abstinence, or vasectomized partner while on treatment and for at least 6 months thereafter
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E.4 | Principal exclusion criteria |
1. Availability of matched sibling donor eligible for stem cell donation 2. Patients with acute promyelocytic leukemia with t(15;17)(q22;q12) and in CR1 3. Patients considered contraindicated for HSCT due to severe concomitant illness (within 3 weeks before scheduled day -6): • patients with severe renal impairment like patients on dialysis or prior renal transplantation or S-creatinine >3.0 x ULN or calculated creatinine-clearance < 60 ml/min • patients with severe pulmonary impairment, DLCOsb (Hb-adjusted)/or FEV1 <50 % or severe dyspnoea at rest or requiring oxygen supply • patients with severe cardiac impairment diagnosed by echocardiography and LVEF <40 % • patients with severe hepatic impairment indicated by hyperbilirubinemia >3x ULN or ALT/AST >5 x ULN 4. Active malignant involvement of the CNS 5. HIV-positivity, active non-controlled infectious disease under treatment (no decrease of CRP or PCT) including active viral liver infection 6. Previous allogeneic HSCT 7. Pleural effusion or ascites > 1.0L 8. Pregnancy or lactation 9. Known hypersensitivity to treosulfan, fludarabine, cyclophosphamide and/or related ingredients 10. Participation in another experimental drug trial within 4 weeks before day -6 of the protocol 11. Non-cooperative behavior or non-compliance 12. Psychiatric diseases or conditions that might compromise the ability to give informed consent
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E.5 End points |
E.5.1 | Primary end point(s) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1 year after haploidentical HSCT |
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E.5.2 | Secondary end point(s) |
• Cumulative incidence of relapse • Relapse-free survival (RFS) • Graft-versus-host disease and relapse-free survival (GRFS) • Cumulative incidence of non-relapse mortality (NRM) a • Cumulative incidence of acute graft-versus-host disease (GVHD) a • Cumulative incidence of chronic GVHD • Toxicities according to the current version of the NCI CTCAE • Engraftment • Chimerism
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1 year after haploidentical HSCT |
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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 | 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 | 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 | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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 | 3 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |