Dose-range Finding Treosulfan-based Conditioning

Study Overview
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Brief Summary
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Evaluation of the safety and efficacy of 3 x 10, 3 x 12 or 3 x 14 g/m² Treosulfan resp., combined with 5 x 30 mg/m² fludarabine prior to allogeneic, hematopoietic stem cell transplantation of patients with hematological malignancies, but non-eligible to standard conditioning treatment.

Official Title
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Allogeneic Hematopoietic Stem Cell Transplantation in Patients With Advanced Hematological Malignancies After Treosulfan-based Conditioning Therapy - A Clinical Phase II Study

Conditions
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Hematological Malignancies

Intervention / Treatment
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* Drug: Treosulfan
* Drug: Treosulfan
* Drug: Treosulfan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with a haematological chemosensitive malignancy indicated for an allogeneic transplantation, but presenting an increased toxicity risk for classical (high-dose busulfan or standard-dose total body irradiation) conditioning therapies (remission criteria ref. to Appendix L): CML in first or subsequent chronic phase NHL in 2nd CR/PR, chemosensitive PR after autologous transplantation ; CLL in 2nd or subsequent CR/PR Relapsed Morbus Hodgkin (MH) after autologous transplantation Multiple Myeloma (MM) stage II and III according to Durie and Salmon AML in 2nd CR/PR or high-risk AML in 1st CR/PR High-risk defined for example by the following: Cytogenetics: -5/5q, -7/7q, del(5q), abnormalities of 3q, complex karyotype (> 3 abnormalities), or PR after 1 cycle of induction therapy ALL in 2nd CR/PR or high-risk ALL in 1st CR/PR High-risk defined as follows: Leukocytes > 3000/µl (B-Linage) or > 100000/µl (T-Linage); Pro-B-ALL, pre-T-ALL Cytogenetics: t(9;22)/BCR-ABL; t(4;11)/ALL1-AF MDS (patients without prior chemotherapy may be included) Availability of an HLA-identical sibling donor (MRD) or HLA-identical unrelated donor (MUD) or one mismatch (out of the 6 standard markers) sibling donor (1 misMRD): • HLA-identity defined by the following markers: A, B, DRB1. DQB1 must be recorded. Age > 18 years Karnofsky Index > 80 % Adequate contraception in female patients of child-bearing potential Co-operative behavior of individual patients Written informed consent Exclusion Criteria: Completely chemotherapy-resistant disease Severe cardiac insufficiency, severe cardio-vascular or other severe concomitant diseases Symptomatic malignant involvement of the CNS Active infectious disease HIV-positive or active hepatitis infection Impaired liver function (Bilirubin > 1.5 x upper normal limit; Transaminases > 3.0 x upper normal limit) Impaired renal function (Creatinine-clearance < 60 ml/min; Serum Creatinine > 1.5 x upper normal limit). Pleural effusion or ascites > 1.0 L Pregnancy or lactation Known hypersensitivity to fludarabine and/or treosulfan Parallel participation in another experimental drug trial

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Treosulfan: 10 g/m² i.v. on 3 consecutive days (day -6 to -4) | Drug: Treosulfan<br>* 10 g/m² i.v. infusion, day -6, -5, -4<br>* Other names: Ovastat;|
| Experimental: 2<br>Treosulfan:12 g/m² i.v. on 3 consecutive days (day -6 to -4) | Drug: Treosulfan<br>* 12 g/m² i.v. infusion, day -6, -5, -4<br>* Other names: Ovastat;|
| Experimental: 3<br>Treosulfan: 14 g/m² i.v. on 3 consecutive days (day -6 to -4) | Drug: Treosulfan<br>* 14 g/m² i.v. infusion, day -6, -5, -4<br>* Other names: Ovastat;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety - Evaluation of feasibility and tolerability of 3 x 10, 12 or 14 g/m² Treosulfan combined with 5 x 30 mg/m² fludarabine prior to allogeneic stem cell transplantation • frequency and severity of TRM until 6 months after transplantation |  | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy - Evaluation of the proportion of relapse- and/or progression free patients six months after transplantation (using standard remission criteria) |  | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Treosulfan, Allogeneic stem cell transplantation, Conditioning therapy