Acute Myeloid Leukaemia (AML), Myelodysplastic Syndrome (MDS) or Multiple Myeloma (MM) Cancer Haematological malignancies
Conditions
Interventions
300 µg RHAMM R3 peptide emulsified with the incomplete Freund's adjuvant on day 3 as well as Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) on days 1 - 5 was administered four times subcuta
Sponsors
University Hospital Ulm (Universitatsklinikum Ulm) (Germany)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Diagnosis of Acute Myeloid Leukaemia (AML), Myelodysplastic Syndrome (MDS) or Multiple Myeloma (MM) 2. AML: up to 25% blasts in the Bone Marrow (BM); MDS: up to 20% blasts in the BM; MM: partial remission (immunofixation still positive or immunoglobulins still detectable in the urine) 3. Human Leukocyte Antigen A2 (HLA-A2) expression 4. RHAMM-messenger Ribonucleic Acid (mRNA) expression 5. Karnofsky Index greater than or equal to 70 or Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2 6. Aged greater than 18 years 7. At least one cycle of treatment with standard chemotherapy for this haematological malignancy preceding the peptide vaccination 8. Survival time at least 6 months 9. Sufficient renal function (creatinine and Blood Urea Nitrogen [BUN] less than threefold of the upper limit) 10. Sufficient liver function tests (Serum Glutamic Oxaloacetic Transaminase [SGOT]/Serum Glutamic Pyruvic Transaminase [SGPT] threefold of the upper limit) 11. Compliance of the patient 12. Informed consent must be obtained in written form
Exclusion criteria
Exclusion criteria: 1. Allogeneic hematopoietic stem cell transplantation in the history planned 2. Central Nervous System (CNS) involvment, severe psychiatric disease 3. Severe partial or global respiratory failure (New York Heart Association [NYHA] stage greater than or equal to III) 4. Immunosuppressive therapy in the last 4 weeks 5. Pregnancy or breastfeeding 6. Females with no sufficient contraception 7. Contradictions against study therapeuticals (including galenic substances) 8. Severe infections 9. Simultaneous participation in another clinical study trial
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| For all patients the BM blood was analysed before and after vaccination using microscopy and standard Fluorescence Activated Cell Sorter (FACS) analysis. Patients with MM were also examined for quantitative immunoglobulins and quantitative free light chains in serum and urine. The frequency of erythrocyte and platelet transfusions and the course of differential blood count were documented. Response criteria were as following: For patients with AML, the criteria by the World Health Organization (WHO) and the International Working Group (IWG) were followed as specified: Complete Response (CR): reduction of blasts in the BM blood to less than 5%, in peripheral blood count: haemoglobin greater than 11 g/dl, neutrophils 1,500/mm^3 or more, platelets 100,000/mm^3 or more Partial Response (PR): reduction of blasts in the BM blood of more than 50%, in peripheral blood count: haemoglobin greater than 11 g/dl, neutrophils 1500/mm^3 or more, platelets 100,000/mm^3 or more Stable Disease (SD): no CR or PR Progressive Disease (PD): increase of blasts in the BM blood by more than 50% or increase of WHO-classification or progress of transfusion requirements For patients with MDS, the criteria by the WHO and the IWG were followed as specified: CR: a complete response was defined as a normocellular with less than 5% blasts with normal maturation of all cell lines, with no evidence of dysplasia, in peripheral blood count: haemoglobin greater than 11 g/dl, neutrophils 1,500/mm^3 or more, platelets 100,000/mm^3 or more PR: blasts decreased by 50% or more over treatment or a less MDS WHO classification than pretreatment, Haematological Improvement (HI): an improvement was defined as a decrease of at least of 50% in transfusion requirements, together with at least an improvement of one ot two cell lineages of the peripheral cell counts but not | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Assessment of toxicity of R3-peptide vaccination: Side effects were documented according to Common Terminology Criteria for Adverse Events v3.0 (CTCAE). Before and three weeks after the fourth vaccination physical examination, body weight, ECOG performance score, laboratory tests (kidney and liver function tests, electrophoresis, electrolytes, C-Reactive Protein [CRP], Lactate Dehydrogenase [LDH], and coagulation tests), chest x-ray, echocardiography, electrocardiography, urine analysis, abdominal sonography and bone-marrow aspiration was performed. For patients with MM additionally quantitative immunoglobulins and quantitative assessment of free light chains in serum and urine were tested. Before each vaccination physical examination, laboratory tests (White Blood Cell [WBC] count, differential blood count, kidney and liver function tests, electrolytes, CRP, LDH, coagulation tests and urine analysis) were performed. To detect autoimmune reactions, we measured Thyroid Stimulating Hormone (TSH), free Triiodothyronine (fT3), free Thyroxine (fT4), as well as Antinuclear Antibody (ANA), CRP and Blood Sedimentation rate (BSG). 2. Interferon (IFN)-gamma and Granzyme B Enzyme-Linked Immunosorbent Spot (ELISpot) assays: IFN-gamma and granzyme B ELISpot assays were performed as previously described to determine specific lysis of RHAMM (peptide) positive target cells according to the manufacturer's instructions (BD, San Diego, USA). We participated in an inter-laboratory test for ELISpot assays. 3. Tetramer staining: The frequency of R3 specific CD8+ T lymphocytes was determined after eight days Mixed Lymphocyte Peptide Culture (MLPC) by staining with anti-CD8 antibody and HLA-A2/R3 tetramer R-Phycoerythrin (PE). HLA-A2/R3 tetramer PE was synthesised at the Lausanne Branch of the Ludwig Institute for Cancer Research. CD8+ T lymphocytes (0.5 - 1 x 10^6) stimulated with irradiated CD8- Antigen- | — |
Countries
Germany
Outcome results
None listed