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

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

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.

Study Overview

• Status: Terminated
• Conditions: Multiple Myeloma
• Intervention / Treatment: Drug: MEDI-551 Maintenance

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: MEDI-551 Treatment Arm; 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; Cycle 1 - Days 1, 8, 15, and 22: 4mg/kg IV Cycles 2-12 - Day 1: 4mg/kg IV

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Investigators: Principal Investigator: Philip Imus, MD, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Study record dates

Study Major Dates

• Study Start (Actual): September 27, 2017
• Primary Completion (Actual): April 15, 2018
• Study Completion (Actual): April 15, 2018

Study Registration Dates

• First Submitted: July 12, 2017
• First Submitted That Met QC Criteria: July 12, 2017
• First Posted (Actual): July 14, 2017

Study Record Updates

• Last Update Posted (Actual): January 14, 2019
• Last Update Submitted That Met QC Criteria: January 10, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Keywords: bone marrow; allogeneic; bone marrow transplant; Medi-551
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell
• Other Study ID Numbers: J1747; IRB00125692 (Other Identifier: JHMIRB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No