A Study of Acute Graft-Versus-Host Disease (GVHD) in Patients Undergoing Allogeneic Stem-Cell Transplantation

NCT02737306 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: PRO 140_CD 03_GVHD
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 8

Brief Summary

This is a Phase II, Randomized, Double-Blind, Placebo-Controlled, Multi-Center Study of the Safety and Efficacy of PRO 140 for Prophylaxis of Acute Graft-Versus-Host Disease in Patients with Acute Myeloid Leukemia (AML) or Myelodysplastic Syndromes (MDS) Undergoing Allogeneic Stem-Cell Transplantation.

Conditions

Graft Vs Host Disease

Keywords

Allogeneic; Stem Cell; Transplantation

Outcome Measures

Primary Outcomes (1)

• Incidence of Acute GVHD by Day 100

  Incidence of Grade II, Grade III or Grade IV acute GVHD by Day-100

  100 days from first treatment (100 Days post treatment)

Secondary Outcomes (11)

• Incidence of Severe and Life-threatening (Grade III and Grade IV) Acute GVHD by Day-100

  100 Days post-treatment

• Incidence of Organ-specific Acute GVHD by Day-100

  100 Days post-treatment

• Donor Engraftment Evaluated by T-cell and Myeloid Chimerism in Peripheral Blood

  365 days post-initial treatment (T1 Visit) (+/- 14 days)

• Neutrophil and Platelet Count Recovery

  100 Days post treatment

• Changes in ECOG Performance Score

  100 Days post treatment visit 1

Study Arms (2)

Placebo

PLACEBO COMPARATOR

In this study, 60 subjects will be randomized to receive either PRO 140 or placebo in a 1:1 ratio (i.e. 30 subjects per arm). PRO 140 or placebo will be administered as a 350 mg subcutaneous injection. Placebo will be administered -2/-3 days before the stem cell infusion, on the day of stem cell infusion (Day 0) and thereafter on days 7, 14, 21, 28, 42, 56, 70, 84 and 98 as per the study schedule of assessments. Each vial of the Placebo contains 5mM Histidine, 15 mM Glycine, 95 mM Sodium Chloride, 0.3% (w/v) Sorbitol, 0.005% (w/v) Polysorbate 20 at a pH of 5.5. Each 350 mg dose of placebo consist of 2 SC injections of placebo (5mM Histidine, 15 mM Glycine, 95 mM Sodium Chloride, 0.3% (w/v) Sorbitol, 0.005% (w/v) Polysorbate 20 at a pH of 5.5) of 2 X 1 mL/inj. on opposite sides of abdomen.

Drug: Placebo

350 mg Pro140

EXPERIMENTAL

In this study, 60 subjects will be randomized to receive either PRO 140 or placebo in a 1:1 ratio (i.e.,30 subjects per arm). PRO 140 or placebo will be administered as a 350 mg subcutaneous injection. PRO 140 will be administered -2/-3 days before the stem cell infusion, on the day of stem cell infusion (Day 0) and thereafter on days 7, 14, 21, 28, 42, 56, 70, 84 and 98 as per the study schedule of assessments. Each vial of the PRO 140 product contains 1.4 mL antibody at 175 mg/ml in a buffer containing 5 mM L-histidine, 15.0 mM glycine, 95 mM sodium chloride, 0.3% (w/v) sorbitol, 0.005% (w/v) polysorbate 20 (Tween 20®), and sterile water for injection, at pH of 5.5. Each 350 mg dose of PRO 140 will consist of 2 SC injections of PRO 140 (2 X 1 mL/inj.) on opposite sides of abdomen.

Drug: PRO 140

Interventions

PRO 140 DRUG

PRO 140 is a humanized IgG4,κ monoclonal antibody (mAb) to the chemokine receptor CCR5.

Also known as: Humanized monoclonal antibody to CCR5

350 mg Pro140

Placebo DRUG

Placebo in parenteral solution.

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must meet all of the following criteria to be included in the study:
• Patients diagnosed with AML or MDS per below:
• Patients with a history of histologically or pathologically confirmed diagnosis of AML and \< 5% blasts in the peripheral blood or bone marrow (per bone marrow aspiration and/or biopsy within 6 weeks prior to screening) scheduled to undergo allogeneic stem-cell transplantation
• Patients with a histologically or pathologically confirmed diagnosis of MDS with \< 10% blasts in the bone marrow (per bone marrow aspiration and/or biopsy within 6 weeks prior to screening) scheduled to undergo allogeneic stem-cell transplantation
• Eastern Cooperative Oncology Group (ECOG) performance status score ≤ 2
• Patients must have normal organ function as defined below:
• Myeloablative allogeneic HCT:
• Males and females, age ≥18 and ≤ 65 years of age
• Total bilirubin ≤ 2 mg/dL (except in patients with Gilbert's Syndrome)
• AST/ALT ≤ 3 times institutional upper limit of normal (except in patients with leukemic infiltration of liver)
• Serum creatinine ≤ 2 mg/dL and creatinine clearance ≥ 60 ml/hr
• Diffusing capacity of the lung for carbon monoxide (DLCO) \> 50% predicted with no symptomatic pulmonary disease
• Cardiac ejection fraction ≥ 50%. If between 40-49% a cardiology consult is required
• Clinically normal resting 12-lead ECG at screening visit or, if abnormal, considered not clinically significant by the PI
• Patients must have a reasonable expectation of ≥ 6 months survival

You may not qualify if:

• Subjects meeting any of the following criteria will be excluded from the study:
• Patients not expected to be available for follow-up for at least 114 days after transplant
• Patients who have received prior allogeneic stem cell-transplantation
• Patients who receive post-transplant high dose cyclophosphamide
• Patients with active central nervous system (CNS) involvement by malignant cells
• Patients receiving other investigational drugs for GVHD. Co-enrollment in other clinical trials that do not include experimental GVHD therapies is allowed.
• Prior use of any experimental or approved CCR5 modulator including maraviroc and PRO 140
• Patients with uncontrolled bacterial, viral or fungal infections including diagnosis of acute viral hepatitis (defined as any active infection with hepatitis A or a new diagnosis of hepatitis B or C within 24 weeks of dosing)
• Currently active second malignancy other than non-melanoma skin cancers
• Presence of fluid collection (ascites, pleural or pericardial effusion) that interferes with methotrexate clearance or makes methotrexate use contraindicated
• Patients who are HIV positive
• Females who are pregnant, lactating, or breastfeeding, or who plan to become pregnant during the study
• Subjects on chronic steroid therapy \> 5 mg/day within 2 weeks of screening except for inhaled, nasal, or topical steroids
• Any other clinical condition that, in the Investigator's judgment, would potentially compromise study compliance or the ability to evaluate safety/efficacy

Sponsors & Collaborators

• CytoDyn, Inc.: lead
• Amarex Clinical Research: collaborator

Study Sites (8)

University of Miami Sylvester Comprehensive Cancer Center

Miami, Florida, 33136, United States

Location

Loyola University Medical Center Cardinal Bernardin Cancer Center

Maywood, Illinois, 60153, United States

Location

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55409, United States

Location

Wake Forest Baptist Health

Winston-Salem, North Carolina, 27157, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Texas Transplant Institute Methodist Hospital

San Antonio, Texas, 78229, United States

Location

West Virginia University Medicine

Morgantown, West Virginia, 26506, United States

Location

MeSH Terms

Conditions

Graft vs Host Disease

Interventions

leronlimab

Condition Hierarchy (Ancestors)

Immune System Diseases

Limitations and Caveats

This study was stopped prior to completion due to lack of enrolment.

Results Point of Contact

• Title: Joseph Meidling Executive Director Clinical Operations
• Organization: CytoDyn

jmeidling@cytodyn.com

(360) 980-8524

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Subjects were randomized to the blinded part of the study using an IRT system. Unblinded pharmacists at clinical sites were notified of the arm to which the subjects were enrolled in order to prepare the appropriate treatment.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 29, 2016
• First Posted: April 13, 2016
• Study Start: May 14, 2017
• Primary Completion: April 14, 2021
• Study Completion: September 30, 2021
• Last Updated: March 12, 2024
• Results First Posted: March 12, 2024

Record last verified: 2022-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (8)