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Study of PRO 140 for Prophylaxis of Acute GVHD in Patients With AML or MDS Undergoing Allogeneic Stem-Cell Transplant. (GVHD)

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ClinicalTrials.gov Identifier: NCT02737306
Recruitment Status : Recruiting
First Posted : April 13, 2016
Last Update Posted : February 2, 2017
Sponsor:
Collaborator:
Amarex Clinical Research
Information provided by (Responsible Party):
CytoDyn, Inc.

Brief Summary:
This is a Phase II, randomized, double-blind, placebo-controlled, multi-center study to evaluate the feasibility of the use of PRO 140 as an add-on therapy to standard GVHD prophylaxis treatment for prevention of acute GVHD in adult patients with AML or MDS undergoing allogeneic stem-cell transplantation.

Condition or disease Intervention/treatment Phase
Graft vs Host Disease Leukemia, Myeloid, Acute Myelodysplastic Syndromes Drug: PRO 140 Drug: Placebo Phase 2

Detailed Description:
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 on Day -3 or Day -2 prior to stem cell infusion, on the day of stem cell infusion (Day 0), and then weekly for 30 days (at Week 1, Week 2, Week 3 and Week 4) after which it will be administered every two weeks for up to 100±7 days (at Week 6, Week 8, Week 10, Week 12 and Week 14). Subjects will return to clinic for two Follow-up visits at 2 weeks after the last treatment visit, and one year after the first treatment visit.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Care Provider)
Primary Purpose: Treatment
Official Title: 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 or Myelodysplastic Syndromes Undergoing Allogeneic Hematopoietic Cell Transplantation.
Study Start Date : November 2016
Estimated Primary Completion Date : December 2017
Estimated Study Completion Date : December 2018


Arm Intervention/treatment
Experimental: PRO 140
30 subjects
Drug: PRO 140
Two 1 mL injections, 175mg/ml each, of PRO 140 to opposite sides of the abdomen.
Other Name: Humanized monoclonal antibody to CCR5

Placebo Comparator: Placebo
30 subjects.
Drug: Placebo
Two 1 mL injections of the Placebo to opposite sides of the abdomen.
Other Name: Placebo Comparator




Primary Outcome Measures :
  1. Incidence of Grade II , Grade III or Grade IV acute GVHD by Day-100 [ Time Frame: 100 Days post treatment ]

Secondary Outcome Measures :
  1. Incidence of severe and life-threatening (Grade III and Grade IV) acute GVHD by Day-100 [ Time Frame: 100 Days post treatment ]
  2. Incidence of organ-specific acute GVHD by Day-100 [ Time Frame: 100 Days post treatment ]
  3. Donor engraftment evaluated by T-cell in peripheral blood [ Time Frame: 365 days post-treatment (+/- 14 days) ]
  4. Donor engraftment evaluated by myeloid chimerism in peripheral blood [ Time Frame: 365 days post-treatment (+/- 14 days) ]
  5. Neutrophil count recovery [ Time Frame: 100 Days post treatment ]
  6. Platelet count recovery [ Time Frame: 100 Days post treatment ]
  7. Changes in ECOG performance score [ Time Frame: 100 Days post treatment ]
  8. GVHD-free survival (GFS) [ Time Frame: 100 Days post treatment ]

Other Outcome Measures:
  1. Tolerability of repeated subcutaneous administration of PRO 140 as assessed by study participants (using Visual Analogue Scale). [ Time Frame: 100 Days post treatment ]
  2. Tolerability of repeated subcutaneous administration of PRO 140 as assessed by investigator-evaluation of injection site reactions. [ Time Frame: 100 Days post treatment ]
  3. Frequency of treatment emergent adverse events and serious adverse events [ Time Frame: 100 Days post treatment ]
  4. AML or MDS relapse rate by Day-100 [ Time Frame: 100 Days post treatment ]
  5. Changes and shifts in laboratory measurements over time [ Time Frame: 365 days post-treatment (+/- 14 days) ]
  6. Changes in Electrocardiogram (ECG) parameters over time [ Time Frame: 365 days post-treatment (+/- 14 days) ]


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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. 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
  2. Eastern Cooperative oncology Group (ECOG) performance status score ≤ 2
  3. Patients must have normal organ function as defined below:

    • If undergoing 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)
      • Aspartate Transaminase (AST) / Alanine Transaminase (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
    • If undergoing non-myeloablative allogeneic HCT:

      • Males and females, age ≥18 and ≤ 75 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 ≥ 40 ml/hr
      • DLCO ≥ 40% predicted with no symptomatic pulmonary disease. If DLCO is ≥35% and < 40% and the patient is asymptomatic, a pulmonary consult is required
      • Cardiac ejection fraction > 30%
      • Clinically normal resting 12-lead ECG at screening visit or, if abnormal, considered not clinically significant by the PI
  4. Patients must have a reasonable expectation of ≥ 6 months survival
  5. The donor-recipient Human Leukocyte Antigen (HLA) match criteria required for participation in this protocol are not research subjects in this study and they must meet criteria as National Marrow Donor Program (NMDP) donors. Procedures for selection of donors and stem cell dose will follow FDA Code of Federal Regulations requirements for Blood Products (21 CFR 640) and Human Cellular and Tissue Based Products (21 CFR 1271). The standard institutional practices for stem cell transplants also will be followed. The donors are:

    • HLA-Identical Sibling (6/6): Minimal typing necessary is serologic typing for class I (AB) and molecular typing for class II (DRB1)
    • Matched Unrelated Donor (8/8): Molecular identity at HLA A, B, C and DRB1 by high-resolution typing
    • Matched Related and Unrelated Donor (7/8): high-resolution molecular typing at the following loci is required: HLA A, B, C and DRB1
  6. Both male and female patients and their partners of childbearing potential must agree to use appropriate birth control methods (birth control pills, barriers, or abstinence) throughout the study duration (excluding women who are not of childbearing potential and men who have been sterilized). Females of childbearing potential must have a negative serum pregnancy test at Screening visit and negative urine pregnancy test prior to receiving the first dose of study drug.
  7. Patients must understand and voluntarily sign an informed consent form

Exclusion Criteria:

  1. Patients not expected to be available for follow-up for at least 114 days after transplant
  2. Patients who have received prior allogeneic stem cell-transplantation
  3. Patients who receive post-transplant high dose cyclophosphamide
  4. Patients with active central nervous system (CNS) involvement by malignant cells
  5. Patients receiving other investigational drugs for GVHD. Co-enrollment in other clinical trials that do not include experimental GVHD therapies is allowed
  6. Prior use of any experimental or approved C-C chemokine receptor type 5 (CCR5) modulators including maraviroc and PRO 140
  7. 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 transplant)
  8. Currently active second malignancy other than non-melanoma skin cancers
  9. Presence of fluid collection (ascites, pleural or pericardial effusion) that interferes with methotrexate clearance or makes methotrexate use contraindicated
  10. Patients who are HIV positive
  11. Females who are pregnant, lactating, or breastfeeding, or who plan to become pregnant during the study
  12. Subjects on chronic steroid therapy > 5 mg/day within 2 weeks of screening except for inhaled, nasal, or topical steroids
  13. Any other clinical condition that, in the Investigator's judgement, would potentially compromise study compliance or the ability to evaluate safety/efficacy

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02737306


Contacts
Contact: Derry Green, PharmD 240-454-6836 derryg@amarexcro.com
Contact: Kush Dhody, MBBS, MS 301-956-2536 kushd@amarexcro.com

Locations
United States, Pennsylvania
University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: David Porter, MD    215-220-9638    david.porter@uphs.upenn.edu   
Contact: Chase Walling    215-220-9638    Christopher.Walling@uphs.upenn.edu   
United States, West Virginia
West Virginia University Medicine Recruiting
Morgantown, West Virginia, United States, 26506
Contact: Pam Bunner    304-598-4511    bunnerp@wvumedicine.org   
Sponsors and Collaborators
CytoDyn, Inc.
Amarex Clinical Research

Responsible Party: CytoDyn, Inc.
ClinicalTrials.gov Identifier: NCT02737306     History of Changes
Other Study ID Numbers: PRO 140_CD 03_GVHD
First Posted: April 13, 2016    Key Record Dates
Last Update Posted: February 2, 2017
Last Verified: February 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by CytoDyn, Inc.:
Allogeneic Stem-Cell Transplantation

Additional relevant MeSH terms:
Syndrome
Leukemia
Myelodysplastic Syndromes
Preleukemia
Leukemia, Myeloid
Graft vs Host Disease
Leukemia, Myeloid, Acute
Disease
Pathologic Processes
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Immune System Diseases
PRO-140 monoclonal antibody
HIV Antibodies
HIV Fusion Inhibitors
Viral Fusion Protein Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Immunologic Factors
Physiological Effects of Drugs