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

• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins (Other)
• Overall Status: Terminated
• CT.gov ID: NCT03218163
• Collaborator: (none)
• Enrollment: 1
• Location: 1
• Arm: 1
• Actual Duration (Months): 6.6
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma	Drug: MEDI-551 Maintenance	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 1 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: Sep 27, 2017
• Actual Primary Completion Date: Apr 15, 2018
• Actual Study Completion Date: Apr 15, 2018

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Progression Free Survival [5 years]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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:

1. 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:

1. 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

1. 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

2. 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.

1. 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;

2. No previous AlloSCT (syngeneic HSCT permissible);

3. Any previous autologous HSCT must have occurred at least 3 months prior to start of conditioning;

4. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2;

5. Life expectancy > 6 months;

6. Adequate end organ function as measured by:

7. Left ventricular ejection fraction ≥ 35% or shortening fraction > 25%

8. 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)

9. Forced expiratory volume at one second (FEV1) and forced vital capacity (FVC) > 40% of predicted

10. Not pregnant or breast-feeding;

11. No uncontrolled infection. Note: Infection is permitted if there is evidence of response to medication;

12. The patient must be able to comprehend and have signed the informed consent.

Exclusion Criteria:

1. Diagnosis of any of the following cancers:

2. POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein (M-protein) and skin changes)

3. Non-secretory myeloma (no measurable protein on Serum Free Lite Assay)

4. HTLV1 / HTLV2 positive

5. Diagnosis of amyloidosis

6. Failed to achieve at least a partial response (PR) to latest therapy;

7. Known history of HIV infection;

8. Systemic infection requiring treatment with antibiotics, antifungal, or antiviral agents within 7 days of registration;

9. History of malignancy other than MM within 5 years of registration, except adequately treated basal or squamous cell skin cancer;

10. History of serious allergy or reaction to any component of the MEDI-551 formulation that would prevent administration;

11. Active hepatitis B as defined by seropositivity for hepatitis B surface antigen or patients with positive hepatitis B core antibody titers.

12. Patients with hepatitis C antibody will be eligible provided that they do not have elevated liver transaminases or other evidence of active hepatitis.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland	United States	21287

Sponsors and Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Investigators

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

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Nov 10, 2017

More Information

Publications

None provided.

• Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• ClinicalTrials.gov Identifier: NCT03218163
• Other Study ID Numbers: J1747; IRB00125692
• First Posted: Jul 14, 2017
• Last Update Posted: Jan 14, 2019
• Last Verified: Jan 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: bone marrow; bone marrow transplant; allogeneic; Medi-551
• Additional relevant MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell

Study Results

Participant Flow

Pre-assignment Detail	This study enrolled 1 participant, but the study was terminated before they could be assigned to the intervention, therefore, 0 participants started the study.

Arm/Group Title	MEDI-551 Treatment Arm
Arm/Group Description	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. MEDI-551 Maintenance: Cycle 1 - Days 1, 8, 15, and 22: 4mg/kg IV Cycles 2-12 - Day 1: 4mg/kg IV
Period Title: Overall Study
STARTED	0
COMPLETED	0
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	MEDI-551 Treatment Arm
Arm/Group Description	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 GVHD, documentation of disease progression, or patient withdrawal for other reasons. MEDI-551 Maintenance: Cycle 1 - Days 1, 8, 15, and 22: 4mg/kg IV Cycles 2-12 - Day 1: 4mg/kg IV
Overall Participants	1
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	1 100%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	1 100%
Male	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	1 100%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (Count of Participants)
United States	1 100%

Outcome Measures

1. Primary Outcome

Title	Progression Free Survival
Description	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.
Time Frame	5 years

Outcome Measure Data

Analysis Population Description

The study was terminated before any participant could start the study and receive intervention. Therefore, no data could be collected.

Arm/Group Title	MEDI-551 Treatment Arm
Arm/Group Description	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 GVHD, documentation of disease progression, or patient withdrawal for other reasons. MEDI-551 Maintenance: Cycle 1 - Days 1, 8, 15, and 22: 4mg/kg IV Cycles 2-12 - Day 1: 4mg/kg IV
Measure Participants	0

Adverse Events

Time Frame	For the duration of the study, about 7 months.
Adverse Event Reporting Description	One participant was enrolled but did not receive study treatment. The participant was monitored for adverse events since enrollment into study (signing informed consent).
Arm/Group Title	MEDI-551 Treatment Arm
Arm/Group Description	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 GVHD, documentation of disease progression, or patient withdrawal for other reasons. MEDI-551 Maintenance: Cycle 1 - Days 1, 8, 15, and 22: 4mg/kg IV Cycles 2-12 - Day 1: 4mg/kg IV
All Cause Mortality
	MEDI-551 Treatment Arm
	Affected / at Risk (%)	# Events
Total	0/1 (0%)
Serious Adverse Events
	MEDI-551 Treatment Arm
	Affected / at Risk (%)	# Events
Total	0/1 (0%)
Other (Not Including Serious) Adverse Events
	MEDI-551 Treatment Arm
	Affected / at Risk (%)	# Events
Total	0/1 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.