MEDI-551 as Maintenance Therapy After Allogeneic Stem Cell Transplant in Multiple Myeloma
Condition: Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: MEDI-551 Maintenance
Intervention description: Cycle 1 - Days 1, 8, 15, and 22: 4mg/kg IV Cycles 2-12 - Day 1: 4mg/kg IV
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 1.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: bone marrow; bone marrow transplant; allogeneic; Medi-551

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.