Patients with AML, myelodysplasia (MDS), ALL, CML in accelerated phase or blastic transformation, CLL, MM or aggressive lymphoma, who underwent allo SCT (both myeloablative and non-myeloablative) followed by DLI for persistent mixed chimerism or smoldering disease. Patient and donor HLA-A2 positive, patient HA-1 positive, donor HA-1 negative. Absence of HA-1 specific immune response 8 weeks after allogeneic stem cell transplantation
Conditions
Interventions
Product Name: HA-1 peptide vaccine
Pharmaceutical Form: Powder and solvent for solution for injection
Sponsors
Leiden University Medical Center
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients with AML, myelodysplasia (MDS), ALL, CML in accelerated phase or blastic transformation, CLL, MM or aggressive lymphoma, who underwent allo SCT (both myeloablative and non-myeloablative) followed by DLI for persistent mixed chimerism or smoldering disease Patient and donor HLA-A2 positive, patient HA-1 positive, donor HA-1 negative. WHO performance status of 0, 1 or 2 (see appendix) No pregnancy, not breast feeding Willing to use of effective contraception during the course of this trial and for at least three months after the last injection. Life expectation of > 3 months No severe psychological disturbances Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: HIV positivity Graft versus host disease grade 3 or 4 At eight weeks after DLI a HA-1 specific immune response (defined by >0.2% of total CD8+ cells) in first three patients Rapidly progressive disease needing cytoreductive treatment At eight weeks after DLI a HA-1 specific immune response (defined by >1.0% of total CD8+ cells) in patients 4-24 if no toxicity >grade II in first three patients Between six and eight weeks after DLI a doubling of percentage HA-1 specific CD8+ cells to a final percentage >0.2% Necessity of persistent treatment with high-dose corticosteroids (> 20 mg prednisone a day), chemotherapy or immunosuppressive drugs.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the safety and toxicity of administration of HA-1 peptide vaccine in HLA-A2 and HA-1 positive patients who had undergone HLA-matched allogeneic stem cell transplantation followed by DLI from a HLA-A2 positive, HA-1 negative, donor showing persistent disease or mixed chimerism eight weeks after DLI (phase 1 study) To evaluate whether an immunologic response can be induced by this vaccination program (primary endpoint of phase 2 study). ;Secondary Objective: To evaluate whether an immunologic response influences chimerism and disease status (secondary endpoint). ;Primary end point(s): Safety and toxicity of administration of HA-1 peptide vaccine in HLA-A2 and HA-1 positive patients who had undergone HLA-matched allogeneic stem cell transplantation followed by DLI from a HLA-A2 positive, HA-1 negative, donor showing persistent disease or mixed chimerism eight weeks after DLI (phase 1 study) Percentage of circulating HA-1 specific T cells during 16 weeks after the first vaccination | — |
Countries
Netherlands
Outcome results
None listed