Dose-range Finding Treosulfan-based Conditioning

Sponsor

medac GmbH (Industry)

Overall Status

Completed

CT.gov ID

NCT01063647

Collaborator

(none)

Enrollment

Locations

Arms

Duration (Months)

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Hematological Malignancies	Drug: Treosulfan Drug: Treosulfan Drug: Treosulfan	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

56 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Nov 1, 2001

Actual Primary Completion Date :

Jun 1, 2005

Actual Study Completion Date :

Jun 1, 2006

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 Treosulfan: 10 g/m² i.v. on 3 consecutive days (day -6 to -4)	Drug: Treosulfan 10 g/m² i.v. infusion, day -6, -5, -4 Other Names: Ovastat
Experimental: 2 Treosulfan:12 g/m² i.v. on 3 consecutive days (day -6 to -4)	Drug: Treosulfan 12 g/m² i.v. infusion, day -6, -5, -4 Other Names: Ovastat
Experimental: 3 Treosulfan: 14 g/m² i.v. on 3 consecutive days (day -6 to -4)	Drug: Treosulfan 14 g/m² i.v. infusion, day -6, -5, -4 Other Names: Ovastat

Arm

Intervention/Treatment

Experimental: 1

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

Drug: Treosulfan

10 g/m² i.v. infusion, day -6, -5, -4

Other Names:

Ovastat

Experimental: 2

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

Drug: Treosulfan

12 g/m² i.v. infusion, day -6, -5, -4

Other Names:

Ovastat

Experimental: 3

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

Drug: Treosulfan

14 g/m² i.v. infusion, day -6, -5, -4

Other Names:

Ovastat

Outcome Measures

Primary Outcome Measures

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

Efficacy - Evaluation of the proportion of relapse- and/or progression free patients six months after transplantation (using standard remission criteria) [6 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Helsinki University Central Hospital	Helsinki	Finland	FIN-00290
2	Charité University Hospital Berlin	Berlin	Germany	12203
3	University Hospital Hamburg Eppendorf	Hamburg	Germany	20246
4	5th Medical Clinic, Clinic North	Nuremberg	Germany	90340
5	University Hospital Rostock	Rostock	Germany	18057
6	Silesian Medical University	Katowice	Poland	40-029
7	Karolinska University Hospital & Karolinska Institute	Stockholm	Sweden	141 86