MEDI-551 as Maintenance Therapy After Allogeneic Stem Cell Transplant in Multiple Myeloma

Study Overview
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Brief Summary
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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.

Official Title
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A Phase II Study of MEDI-551 as Maintenance Therapy After Allogeneic Stem Cell Transplant in Patients With Newly Diagnosed Poor-risk or Relapsed Multiple Myeloma

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Drug: MEDI-551 Maintenance


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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; 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. 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; No previous AlloSCT (syngeneic HSCT permissible); Any previous autologous HSCT must have occurred at least 3 months prior to start of conditioning; Eastern Cooperative Oncology Group (ECOG) performance status of 0-2; Life expectancy > 6 months; Adequate end organ function as measured by: Left ventricular ejection fraction ≥ 35% or shortening fraction > 25% 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) Forced expiratory volume at one second (FEV1) and forced vital capacity (FVC) > 40% of predicted Not pregnant or breast-feeding; No uncontrolled infection. Note: Infection is permitted if there is evidence of response to medication; The patient must be able to comprehend and have signed the informed consent. Exclusion Criteria: Diagnosis of any of the following cancers: POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein (M-protein) and skin changes) Non-secretory myeloma (no measurable protein on Serum Free Lite Assay) HTLV1 / HTLV2 positive Diagnosis of amyloidosis Failed to achieve at least a partial response (PR) to latest therapy; Known history of HIV infection; Systemic infection requiring treatment with antibiotics, antifungal, or antiviral agents within 7 days of registration; History of malignancy other than MM within 5 years of registration, except adequately treated basal or squamous cell skin cancer; History of serious allergy or reaction to any component of the MEDI-551 formulation that would prevent administration; Active hepatitis B as defined by seropositivity for hepatitis B surface antigen or patients with positive hepatitis B core antibody titers. Patients with hepatitis C antibody will be eligible provided that they do not have elevated liver transaminases or other evidence of active hepatitis.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MEDI-551 Treatment Arm<br>Medi-551 maintenance therapy will be initiated on Day 60, Day 90, or Day 120 of NM-AlloSCT based on the eligibility criteria for the initiation of maintenance therapy as described in Section 3.1. MEDI-551 will be administered on 28-day cycles at a dose of 4mg/kg, as an IV infusion over 60 ±15 minutes. Infusion sets must contain a 0.2 micron in-line filter. MEDI-551 will be administered on days 1, 8, 15, and 22 of cycle 1, then 4mg/kg IV on day1 of cycles 2 through 12. Treatment may be stopped earlier if there is unacceptable toxicity, development of Grade 3 or 4 graft-versus-host disease (GVHD), documentation of disease progression, or patient withdrawal for other reasons. | Drug: MEDI-551 Maintenance<br>* Cycle 1 - Days 1, 8, 15, and 22: 4mg/kg IV Cycles 2-12 - Day 1: 4mg/kg IV<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival | The progression free survival (PFS) 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. | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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bone marrow, bone marrow transplant, allogeneic, Medi-551