Bortezomib therapy combined with donor lymphocyte infusion in patients with relapsed Multiple Myeloma following allogeneic stem cell transplantatio
- Conditions
- Multiple Myeloma/ Multiple Myeloom/ Morbus KahlerAllogeneic stem cell transplantation/allogene stamceltransplantatieDonor lymphocyte infusion/Donor lymfocyten infusieBortezomib
- Registration Number
- NL-OMON25090
- Lead Sponsor
- MC Utrecht, afdeling hematologie
- Brief Summary
1. Lokhorst HM, Wu K, Verdonck LF et al. The occurrence of graft-versus-host disease is the major predictive factor for response to donor lymphocyte infusions in multiple myeloma. Blood 2004;103:4362-4364. 2. van de Donk NW, Kroger N, Hegenbart U et al. Remarkable activity of novel agents bortezomib and thalidomide in patients not responding to donor lymphocyte infusions following nonmyeloablative allogeneic stem cell transplantation in multiple myeloma. Blood 2006;107:3415-3416. 3. Kroger N, Shimoni A, Zagrivnaja M et al. Low-dose thalidomide and donor lymphocyte infusion as adoptive immunotherapy after allogeneic stem cell transplantation in patients with multiple myeloma. Blood 2004;104:3361-3363. 4.Sun K, Welniak LA, Panoskaltsis-Mortari A et al. Inhibition of acute graft-versus-host disease with retention of graft-versus-tumor effects by the proteasome inhibitor bortezomib. Proc.Natl.Acad.Sci.U.S.A 2004;101:8120-8125
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Pending
- Sex
- Not specified
- Target Recruitment
- 20
1. Male or female and at least 18 years-of-age;
2. MM patients with any type of relapse or progressive disease following (non) myeloablative allo-SCT for which DLI is considered a treatment option (including patients previously participating in Hovon 54 or Hovon 65 studies);
3. Informed consent;
4. Haematological parameters; Hb > 4.0 mmol/L, leucocytes > 1.0¡Á109/L , thrombocytes > 25 ¡Á109/L, with or without transfusion
1. Use of the immunosuppressive drugs cyclosporin, MMF, or corticosteroids;
2. Existing GvHD > grade A;
3. Any non-hematological toxicity CTC grade ¡Ý 3;
4. Neuropathy and/or neuropathic pain CTC grade ¡Ý 2;
5. Pregnancy;
6. History of allergic reaction to compounds containing boron or mannitol;
7. Uncontrolled or severe cardiovascular disease, including myocardial infarctiin within 6 months, NYHA class III of IV heart failure (appendix E), uncontrolled angina, clinically significant pericardial disease or cardiac amyloidosis;
8. Previous use of bortezomib is not an exclusion criterion, however patients refractory to bortezomib during previous treatments are excluded from this study.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method The primary outcome is response rate. The included patients will be analysed with analysis of the m-protein at entry, after bortezomib cycle 2, 4, 6, 8 and before administration of DLI or before cycle 4,6,8 if no more DLI is given. After each DLI before administration of bortezomib<br>cycle 3, 5, 7 and in follow up every 2 months. Bone marrow examination<br>will be done on indication, for example confirmation of CR.<br>
- Secondary Outcome Measures
Name Time Method Secondary outcomes are evaluated at the same time points as the primary outcome. Blood samples for experimental mmunology are taken before first gift bortezomib in cycle 1, before first DLI, before first gift bortezomib cycle 3, before DLI nr 2, before first gift bortezomib<br>cycle 5, before DLI nr 3, before first gift bortezomib cycle 7 and by stopping treatment and/or by occurring GvHD.<br>