Total Marrow Irradiation and High-dose Melphalan for Double Autologous Hematopoietic Stem Cell Transplantation in Multiple Myeloma

Multiple Myeloma Clinical Trial

Official title:

Efficacy and Safety of Double Autologous Hematopoietic Stem Cell Transplantation With Sequential Use of Total Marrow Irradiation and High-dose Melphalan in Multiple Myeloma

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT01665014
• Other study ID #: TMI MM1
• Status: Not yet recruiting
• Phase: Phase 2
• First received: August 11, 2012
• Last updated: August 16, 2012
• Start date: August 2012
• Est. completion date: August 2016

Study information

• Verified date: August 2012
• Source: Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice
• Contact: Sebastian Giebel, MD
• Phone: 0048322788523
• Email: sgiebel[@]io.gliwice.pl
• Is FDA regulated: No
• Health authority: Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate if the use total marrow irradiation (TMI) as a sole preparation for the first autologous hematopoietic stem cell transplantation (autoHSCT) followed by high-dose melphalan used prior to second autoHSCT is safe and effective in patients with multiple myeloma (MM).

Description:

AutoHSCT is a standard treatment of patients with MM. According to soem clinical evidence double autoHSCT provides survival advantage compared to a single procedure. Most frequently used conditioning regimen consists pf high doses of melphalan (HD-MEL). In some studies it was used in combination with total body irradiation (TBI), which, however was associated with significant toxicity. In our center the standard procedure includes TBI as a single treatment at 1st autoHSCT and HD-Mel at 2nd autoHSCT.

As in MM malignant plasma cells are localized almost exclusively in bone marrow there is rationale to limit irradiation to bones. For this purpose in the current study we substitute TBI with TMI. Additional boosts are provided for active sites of disease based on PET/CT imaging. Our intention is to minimize toxicity while maintaining the treatment efficacy.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 50
• Est. completion date: August 2016
• Est. primary completion date: December 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Age 18-65 years

• Diagnosis of multiple myeloma

• PR, VGPR or CR at inclusion

• Performance status WHO 0-1

• Written informed consent

Exclusion Criteria:

• Organ dysfunction: elevated ALT, AST, bilirubin, AF; creatinine >1.5 upper normal limit; LVEF <45%

• Active infection

• Unstable diabetes

• Psychiatric diseases

• History of high-dose chemotherapy or irradiation

• Second malignancy

• Pregnancy

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Radiation:
• Total marrow irradiation
Mobilization of stem cells with the use of cytarabine 1.6 g/m2 followed by filgrastim 480 ug/d. Conditioning for the 1st autoHSCT: total marrow irradiation 4 Gy on days -3,-2,-1 (total 12 Gy). Conditioning for 2nd autoHSCT performed 3-4 months after the 1st one: melphalan 100 mg/m2 on days -2,-3 (total 200 mg/m2)

Locations

Country	Name	City	State
Poland	Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch	Gliwice

Sponsors (1)

Lead Sponsor	Collaborator
Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice

Country where clinical trial is conducted

Poland, 

References & Publications (1)

Somlo G, Spielberger R, Frankel P, Karanes C, Krishnan A, Parker P, Popplewell L, Sahebi F, Kogut N, Snyder D, Liu A, Schultheiss T, Forman S, Wong JY. Total marrow irradiation: a new ablative regimen as part of tandem autologous stem cell transplantation for patients with multiple myeloma. Clin Cancer Res. 2011 Jan 1;17(1):174-82. doi: 10.1158/1078-0432.CCR-10-1912. Epub 2010 Nov 3. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Rate of severe adverse events		one year	Yes
Primary	Progression-free survival		three years	No
Secondary	Rate of complete and very good partial responses		six months	No