Dose-range Finding Treosulfan-based Conditioning - Full Text View

Purpose

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	Intervention	Phase
Hematological Malignancies	Drug: Treosulfan	Phase 1 Phase 2

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: 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

Resource links provided by NLM:

MedlinePlus related topics: Cancer

U.S. FDA Resources

Further study details as provided by medac GmbH:

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 [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Efficacy - Evaluation of the proportion of relapse- and/or progression free patients six months after transplantation (using standard remission criteria) [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]

Enrollment:	56
Study Start Date:	November 2001
Study Completion Date:	June 2006
Primary Completion Date:	June 2005 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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 Name: 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 Name: 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 Name: Ovastat

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Please refer to this study by its ClinicalTrials.gov identifier: NCT01063647

Locations

Finland
Helsinki University Central Hospital
Helsinki, Finland, FIN-00290
Germany
Charité University Hospital Berlin
Berlin, Germany, 12203
University Hospital Hamburg Eppendorf
Hamburg, Germany, 20246
5th Medical Clinic, Clinic North
Nuremberg, Germany, 90340
University Hospital Rostock
Rostock, Germany, 18057
Poland
Silesian Medical University
Katowice, Poland, 40-029
Sweden
Karolinska University Hospital & Karolinska Institute
Stockholm, Sweden, 141 86

Sponsors and Collaborators

medac GmbH

Investigators

Principal Investigator:

Mathias Freund, MD

University Hospital Rostock

More Information

No publications provided

Responsible Party:	Joachim Baumgart, PhD, medac GmbH
ClinicalTrials.gov Identifier:	NCT01063647 History of Changes
Other Study ID Numbers:	MC-FludT.6/L
Study First Received:	February 3, 2010
Last Updated:	February 4, 2010
Health Authority:	Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by medac GmbH:

Treosulfan
Allogeneic stem cell transplantation
Conditioning therapy

Additional relevant MeSH terms:

Neoplasms
Hematologic Neoplasms
Neoplasms by Site
Hematologic Diseases
Treosulfan
Busulfan
Antineoplastic Agents, Alkylating
Alkylating Agents

Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Myeloablative Agonists

ClinicalTrials.gov processed this record on May 22, 2013