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Graft Vs Host DiseasePhase 2GVHDNCT02737306

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

A Phase 2 study testing PRO 140 in people with Graft Vs Host Disease, run by CytoDyn, Inc. at 8 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
Graft Vs Host Disease
What is being tested?
PRO 140
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
11 participants
Where
8 sitesUnited States
Study dates
14 May 2017to 30 Sep 2021
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
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  • 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
  • The donor-recipient 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 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
  • 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.
  • Patients must understand and voluntarily sign an informed consent form

Who cannot join

  • 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.
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  • 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

Trial locations and contacts

8 sites in 1 country.

8 sites in 1 country

United States8 sites

  • Barbara Ann Karmanos Cancer Institute

    Detroit, Michigan, 48201

  • Loyola University Medical Center Cardinal Bernardin Cancer Center

    Maywood, Illinois, 60153

  • University of Miami Sylvester Comprehensive Cancer Center

    Miami, Florida, 33136

  • University of Minnesota

    Minneapolis, Minnesota, 55409

  • West Virginia University Medicine

    Morgantown, West Virginia, 26506

  • University of Pennsylvania

    Philadelphia, Pennsylvania, 19104

  • Texas Transplant Institute Methodist Hospital

    San Antonio, Texas, 78229

  • Wake Forest Baptist Health

    Winston-Salem, North Carolina, 27157

Other trials in United States

About this study

Official title: A Phase II, Randomized, Double-Blind, Placebo-Controlled 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)

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.

Read the detailed description

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 HCT.

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.

Being tested
PRO 140, Placebo
Keywords
Allogeneic, Stem Cell, Transplantation
Medical subject headings
Graft vs Host Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PRO 140Drug

    Also called Humanized monoclonal antibody to CCR5

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

  • PlaceboDrug

    Placebo in parenteral solution.

Study groups in NCT02737306
Study groupRoleWhat they receive
PlaceboPlacebo comparatorIn 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.
Receives: Drug: Placebo
350 mg Pro140ExperimentalIn 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.
Receives: Drug: PRO 140

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Incidence of Acute GVHD by Day 100

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

    Measured: 100 days from first treatment (100 Days post treatment)

Secondary outcomes (11)

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

    The number and percentages of subjects with severe and life-threatening (Grade III and Grade IV) acute GVHD by Day-100 will be presented. Chi-square/ Fisher's exact test will be used to compare the incidence between the treatment groups.

    Measured: 100 Days post-treatment

  2. Incidence of Organ-specific Acute GVHD by Day-100

    The number and percentages of subjects with organ-specific acute GVHD by Day-100 will be presented by organ category. Chi-square/ Fisher's exact test will be used to compare the incidence between the treatment groups.

    Measured: 100 Days post-treatment

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

    The number and percentages of subjects with donor engraftment failure evaluated by T-cell and myeloid chimerism in peripheral blood will be presented by different treatment groups. Chi-square/ Fisher's exact test will be used to compare the incidence of donor engraftment failure.

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

  4. Neutrophil and Platelet Count Recovery

    The number and percentages of subjects with neutrophil and platelet count recovery will be presented. Chi-square/ Fisher's exact test will be used to compare the incidence of neutrophil recovery and of platelet recovery between treatment groups.

    Measured: 100 Days post treatment

  5. Changes in ECOG Performance Score

    The raw and change from baseline in ECOG performance score will be summarized for each assessment scheduled visit (i.e., Screening visit, Treatment Visits 1, 4, 7, 9, 11, Follow-up Visit 1and Unscheduled Visit(s)). Descriptive statistics (n, mean, standard deviation, median, minimum and maximum) will be presented by treatment group. If the Normality assumption is met, t-test will be used to compare the mean of ECOG performance score between the treatment groups and if the Normality assumption is not met, a non-parametric method will be used.

    Measured: 100 Days post treatment visit 1

  6. GVHD-free Survival (GFS)

    GFS will be defined as the elapsed time between the date of transplant until GVHD related death. GVHD-free survival will be compared between the treatment groups using Log-rank test and Kaplan-Meier methods will be used to depict the survival curves.

    Measured: 100 Days post treatment visit T1

  7. Tolerability of Repeated Subcutaneous Administration of PRO 140 as Assessed by Study Participants (Using Visual Analogue Scale) and by Investigator-evaluation of Injection Site Reactions

    All data from tolerability assessments of repeated subcutaneous administration of PRO 140 as assessed by study participants and by investigator-evaluation of injection site reactions will be summarized using n, mean, Standard Deviation (SD), minimum and maximum values.

    Measured: 365 days post-treatment (+/- 14 days)

  8. Frequency of Treatment Emergent Adverse Events and Serious Adverse Events

    Frequency of treatment emergent adverse events and treatment emergent serious adverse events.

    Measured: 100 Days post treatment

  9. AML or MDS Relapse Rate by Day-100

    AML or MDS relapse rate by Day-100 will be summarized and present by treatment groups.

    Measured: 100 Days post treatment

  10. Changes and Shifts in Laboratory Measurements Over Time

    Safety Assessment- The laboratory measurements will include Routine CBC, Biochemistry and Urinalysis.

    • Routine CBC includes hemoglobin, hematocrit (HCT), red blood cell (RBC) count, white blood cell (WBC) count, WBC differential count (%), absolute neutrophils count (ANC) and platelets count.
    • Biochemistry profile includes assessment of Hepatic function indicators: total and direct bilirubin, alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), total protein, Lactate dehydrogenase (LDH); Renal function indicators: Blood Urea Nitrogen (BUN), creatinine; Electrolytes: sodium, potassium, chloride, calcium and bicarbonate; Other: glucose (random), cholesterol (total)
    • Urinalysis for color, appearance, specific gravity, pH, protein, glucose, occult blood, ketones, RBC, WBC, epithelial cells, bacteria, casts, crystals

    Measured: 365 days post-treatment (+/- 14 days)

  11. Changes in Electrocardiogram (ECG) Parameters Over Time

    Safety Assessment-The following ECG parameters will be evaluated: ventricular rate (beats per minute), PR interval (msec), QRS interval (msec), QT interval (msec), and QTc interval (msec).

    Measured: 365 days post-treatment (+/- 14 days)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Apr 2016 (estimated)
  2. Study start14 May 2017
  3. Primary completion14 Apr 2021
  4. Study completion30 Sep 2021

Why it stopped: Study terminated due to lack of enrolment..

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
11 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02737306
Sponsor's protocol ID
PRO 140_CD 03_GVHD
Acronym
GVHD
Status last verified
Jan 2022
First submitted
29 Mar 2016
Last updated
12 Mar 2024
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing PRO 140 in people with Graft Vs Host Disease, run by CytoDyn, Inc. at 8 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 21 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 12 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 12 Mar 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of Acute GVHD by Day 100 (time frame: 100 days from first treatment (100 Days post treatment)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02737306.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Mar 2024.

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