Dose-range Finding Treosulfan-based Conditioning

Medac

Status and phase: Completed; Phase 2; Phase 1

Conditions: Hematological Malignancies

Treatments: Drug: Treosulfan

Study type: Interventional

Funder types: Industry

Identifiers

NCT01063647

MC-FludT.6/L

Details and patient eligibility

About

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.

Enrollment: 56 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. 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)

2. 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.

3. Age > 18 years

4. Karnofsky Index > 80 %

5. Adequate contraception in female patients of child-bearing potential

6. Co-operative behavior of individual patients

7. Written informed consent

Exclusion criteria

1. Completely chemotherapy-resistant disease
2. Severe cardiac insufficiency, severe cardio-vascular or other severe concomitant diseases
3. Symptomatic malignant involvement of the CNS
4. Active infectious disease
5. HIV-positive or active hepatitis infection
6. Impaired liver function (Bilirubin > 1.5 x upper normal limit; Transaminases > 3.0 x upper normal limit)
7. Impaired renal function (Creatinine-clearance < 60 ml/min; Serum Creatinine > 1.5 x upper normal limit).
8. Pleural effusion or ascites > 1.0 L
9. Pregnancy or lactation
10. Known hypersensitivity to fludarabine and/or treosulfan
11. Parallel participation in another experimental drug trial

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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56 participants in 3 patient groups

1

Experimental group

Description:

Treosulfan: 10 g/m² i.v. on 3 consecutive days (day -6 to -4)

Treatment:

Drug: Treosulfan

Drug: Treosulfan

Drug: Treosulfan

2

Experimental group

Description:

Treosulfan:12 g/m² i.v. on 3 consecutive days (day -6 to -4)

Treatment:

Drug: Treosulfan

Drug: Treosulfan

Drug: Treosulfan

3

Experimental group

Description:

Treosulfan: 14 g/m² i.v. on 3 consecutive days (day -6 to -4)

Treatment:

Drug: Treosulfan

Drug: Treosulfan

Drug: Treosulfan