medi-551 as maintenance therapy after allogeneic stem cell transplant in multiple myeloma

Conditions: Multiple Myeloma

Summary: determine the progression free survival of high-risk or relapsed multiple myeloma (mm) patients undergoing non-myeloablative bone marrow allogeneic transplantation (nm-allosct) followed by maintenance therapy with medi-551.


Eligibility criteria:
inclusion criteria: 1. previous diagnosis of mm based on standard criteria as defined in appendix a (diagnostic criteria for mm). diagnostic studies need not be performed within 30 days of registration; 2. patients must meet one of the disease criteria outlined in either a, b, or c: a. patients with newly diagnosed high-risk mm achieving a partial response (pr) or better at the time of enrollment in response to systemic anti-myeloma therapy, which may include autologous hematopoietic stem cell transplant (hsct). high risk is defined by the presence of any one of the following: i. high-risk chromosomal translocations by fluorescent in situ hybridization (fish): t(4;14), t(14;16), t(14;20), del(17p), del(1p), amplification 1q ii. myeloma prognostic risk signature 70-gene expression profiling (myprs gep-70) high-risk signature either at diagnosis or at time of registration for the study iii. lactate dehydrogenase (ldh) \> 300 u/l at diagnosis iv. plasma cell leukemia v. relapse from prior therapy within 12 months b. patients with high-risk mm with at least 1 prior progression in pr or better in response to salvage systemic anti-myeloma therapy at the time of enrollment c. patients with standard risk mm with 1 prior progression within 18 months from an autologous hsct and in very good partial remission (vgpr) or better in response to salvage systemic anti-myeloma therapy at the time of enrollment. 3. patients must have a suitable first-degree or second-degree related, human leukocyte antigen (hla)-haploidentical or hla-matched stem cell donor. the donor and recipient must be identical at least one allele of each of the following genetic loci: hla-a, hla-b, hla-cw, major histocompatibility complex, class ii, dr beta 1 (hla-drb1), and major histocompatibility complex, class ii, dq beta 1 (hla-dqb1). a minimum match of 5/10 is therefore required, and will be considered sufficient evidence that the donor and recipient share one hla haplotype; 4. no previous allosct (syngeneic hsct permissible); 5. any previous autologous hsct must have occurred at least 3 months prior to start of conditioning; 6. eastern cooperative oncology group (ecog) performance status of 0-2; 7. life expectancy \> 6 months; 8. adequate end organ function as measured by: 1. left ventricular ejection fraction ≥ 35% or shortening fraction \> 25% 2. bilirubin ≤ 3.0 mg/dl (unless due to gilbert's syndrome or hemolysis), and alanine aminotransferase (alt) and aspartate transaminase (ast) \< 5x upper limit of normal (uln) 3. forced expiratory volume at one second (fev1) and forced vital capacity (fvc) \> 40% of predicted 9. not pregnant or breast-feeding; 10. no uncontrolled infection. note: infection is permitted if there is evidence of response to medication; 11. the patient must be able to comprehend and have signed the informed consent. exclusion criteria: 1. diagnosis of any of the following cancers: 1. poems syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein (m-protein) and skin changes) 2. non-secretory myeloma (no measurable protein on serum free lite assay) 3. htlv1 / htlv2 positive 4. diagnosis of amyloidosis 2. failed to achieve at least a partial response (pr) to latest therapy; 3. known history of hiv infection; 4. systemic infection requiring treatment with antibiotics, antifungal, or antiviral agents within 7 days of registration; 5. history of malignancy other than mm within 5 years of registration, except adequately treated basal or squamous cell skin cancer; 6. history of serious allergy or reaction to any component of the medi-551 formulation that would prevent administration; 7. active hepatitis b as defined by seropositivity for hepatitis b surface antigen or patients with positive hepatitis b core antibody titers. 8. patients with hepatitis c antibody will be eligible provided that they do not have elevated liver transaminases or other evidence of active hepatitis.

Keywords: bone marrow bone marrow transplant allogeneic medi-551