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Trial record 3 of 414 for:    Gonadotrophin, Chorionic AND Choriogonadotropin Alfa

Study of Pregnyl as Adjunct Therapy for High-Risk or Refractory Acute GVHD

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ClinicalTrials.gov Identifier: NCT02525029
Recruitment Status : Recruiting
First Posted : August 17, 2015
Last Update Posted : December 6, 2018
Sponsor:
Information provided by (Responsible Party):
Masonic Cancer Center, University of Minnesota

Brief Summary:
The purpose of this study is to determine the maximum tolerated dose (MTD) of Pregnyl® when given in combination with standard immunosuppressive therapy in pediatric and adult patients with high-risk (Arm 1) or refractory/dependent (Arm 2) aGVHD.

Condition or disease Intervention/treatment Phase
Graft vs Host Disease Drug: Pregnyl® Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 66 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Supportive Care
Official Title: Phase I/II Study of Human Chorionic Gonadotropin and Epidermal Growth Factor Supplementation (Pregnyl®) to Support Tolerance and Repair As Adjunct Therapy in High-Risk or Refractory Acute Graft-Versus-Host Disease
Study Start Date : March 2016
Estimated Primary Completion Date : August 2019
Estimated Study Completion Date : March 2021


Arm Intervention/treatment
Experimental: 1: High-Risk aGVHD

Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses.

Individual patient dose reductions: If a patient has toxicity that meets the definition of dose limiting, the patient can drop down one dose level for the next injection and continue treatment. If the patient is enrolled in the phase I component, the event must be reported as a DLT per section 11. If the same patient experiences a second DLT, the patient will discontinue treatment.

Continue protocol treatment through day 7. Assess response at day 7:

  1. If a complete or partial response, continue protocol treatment followed by hCG maintenance twice weekly for 10 doses beginning day 9 to 12.
  2. If no response, the patient will be taken off study treatment.
Drug: Pregnyl®

ARM 1: High-Risk aGVHD

Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7:

  • If a complete or partial response, continue protocol treatment followed by hCG maintenance twice weekly for 10 doses beginning day 9 to 12.
  • If no response, the patient will be taken off study treatment

Doses for both arms:

  • Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic.
  • Phase II: the dose of Pregnyl will be that identified as the MTD during phase I.
Other Name: Human chorionic gonadotropin (hCG)

Experimental: 2a: Steroid-Dependent aGVHD

Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses.

Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment. If the patient is enrolled in the phase I component, the event must be reported as a DLT per section section 11. If the same patient experiences a second DLT, the patient will discontinue treatment.

Continue protocol treatment through day 14. Assess response at day 14:

  1. If a complete or partial response, continue protocol treatment followed by hCG at the assigned dose maintenance twice weekly for 10 doses beginning day 15 to 17.
  2. If no response, the patient will be taken off study treatment
Drug: Pregnyl®

ARM 2a: Steroid Dependent aGVHD

Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7:

  • If a complete or partial response, continue protocol treatment followed by hCG maintenance twice weekly for 10 doses beginning day 9 to 12.
  • If no response, the patient will be taken off study treatment

Doses for both arms:

  • Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic.
  • Phase II: the dose of Pregnyl will be that identified as the MTD during phase I.
Other Name: Human chorionic gonadotropin (hCG)

Experimental: 2b: Steroid-Refractory aGVHD

Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses.

Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment. If the patient is enrolled in the phase I component, the event must be reported as a DLT per section section 11. If the same patient experiences a second DLT, the patient will discontinue treatment.

Continue protocol treatment through day 14. Assess response at day 14:

  1. If a complete or partial response, continue protocol treatment followed by hCG at the assigned dose maintenance twice weekly for 10 doses beginning day 15 to 17.
  2. If no response, the patient will be taken off study treatment
Drug: Pregnyl®

ARM 2b: Steroid-Refractory aGVHD

Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 7 doses through day 14:

  • If a complete or partial response, continue protocol treatment followed by hCG at the assigned dose maintenance twice weekly for 10 doses beginning day 15 to 17.
  • If no response, the patient will be taken off study treatment

Doses for both arms:

  • Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic.
  • Phase II: the dose of Pregnyl will be that identified as the MTD during phase I.
Other Name: Human chorionic gonadotropin (hCG)




Primary Outcome Measures :
  1. Phase I: MTD [ Time Frame: Day 14 after initiation of protocol therapy ]
    Maximum tolerated dose (MTD) of Pregnyl® when given with standard immunosuppressive therapy in pediatric and adult patients with high-risk or refractory acute graft-versus-host disease (aGVHD).

  2. Phase II: Number of Patients with Complete Response [ Time Frame: Day 28 after initiation of protocol therapy ]
    Percentage of complete response among surviving patients at day 28 after initiation of protocol therapy in pediatric and adult patients with high-risk (Arm 1) or refractory (Arm 2) aGVHD. Complete response is defined as a Stage of 0 for all organs with no additional intervening therapy for their GVHD.

  3. Phase II: Number of Patients with Partial Response [ Time Frame: Day 28 after initiation of protocol therapy ]
    Percentage of partial response among surviving patients at day 28 after initiation of protocol therapy in pediatric and adult patients with high-risk (Arm 1) or refractory (Arm 2) aGVHD. Partial response is defined as improvement by at least 1 stage in all involved organs without progression in others with no additional intervening therapy for their GVHD.

  4. Phase II: Number of Patients with Mixed Response [ Time Frame: Day 28 after initiation of protocol therapy ]
    Percentage of mixed response among surviving patients at day 28 after initiation of protocol therapy in pediatric and adult patients with high-risk (Arm 1) or refractory (Arm 2) aGVHD. Mixed Response is defined as improvement in one organ with deterioration in another organ manifesting symptoms of GVHD or development of symptoms of GVHD in a new organ.

  5. Phase II: Number of Patients with No Response [ Time Frame: Day 28 after initiation of protocol therapy ]
    Percentage of no response among surviving patients at day 28 after initiation of protocol therapy in pediatric and adult patients with high-risk (Arm 1) or refractory (Arm 2) aGVHD. No response is defined as deterioration of any organ involved.


Secondary Outcome Measures :
  1. Number of Participants with Adverse Events as a Measure of Safety and Feasibility of hCG Supplementation with Pregnyl® [ Time Frame: Day 70 after initiation of protocol therapy ]
    Safety and feasibility of hCG supplementation with Pregnyl® in combination with standard immunosuppressive therapy in pediatric and adult patients with high-risk or refractory aGVHD.

  2. Number of Participants with Incidence of aGVHD Flare [ Time Frame: Day 28 after initiation of protocol therapy ]
    Incidence of acute GVHD flare after CR/PR requiring increase of steroids or other systemic treatment at days 28 and 56.

  3. Number of Participants with Incidence of aGVHD Flare [ Time Frame: Day 56 after initiation of protocol therapy ]
    Incidence of acute GVHD flare after CR/PR requiring increase of steroids or other systemic treatment at days 28 and 56.

  4. Rate of participants who fail treatment at Day 28 [ Time Frame: Day 28 after initiation of protocol therapy ]
    Rate of treatment failure for acute GVHD at days 28 and 56 after initiation of protocol therapy to historical controls.

  5. Rate of participants who fail treatment at Day 56 [ Time Frame: Day 56 after initiation of protocol therapy ]
    Rate of treatment failure for acute GVHD at days 28 and 56 after initiation of protocol therapy to historical controls.



Information from the National Library of Medicine

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Ages Eligible for Study:   up to 76 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Acute graft versus host disease (GVHD) fitting one of the following categories:

    • High-Risk aGVHD (ARM 1): Pediatric or adult (ages 12-76 years) HCT recipients with high-risk acute GVHD, as determined by the refined MN acute GVHD risk score: http://z.umn.edu/MNAcuteGVHDRiskScore OR high risk on the basis of blood biomarkers (Ann Arbor Score 3 or amphiregulin ≥ 33 pg/ml) or
    • Steroid-Refractory aGVHD (ARM 2): Pediatric or adult (ages 12-76 years) HCT recipient with grade II-IV steroid refractory or steroid-dependent acute GVHD, defined as any one of the following:

      • No response of acute GVHD after at least 4 days of systemic corticosteroids of at least 2 mg/kg prednisone or equivalent
      • Progression of acute GVHD within 3 days of systemic corticosteroids of at least 2 mg/kg prednisone or equivalent
      • Failure to improve to at least grade II acute GVHD after 14 days of systemic corticosteroids, with initial doses of at least 2 mg/kg prednisone or equivalent
      • Flare of acute GVHD of at least grade II/IV severity despite tapering dose of steroids being > 0.5 mg/kg/day.
  • Adequate organ function at study enrollment defined as:

    • Renal: 1.73m2Serum creatinine ≤2.5x upper limit of normal (ULN)
    • Cardiac: Left ventricular ejection fraction (LVEF) ≥ 35%
  • Voluntary written consent (adult or parent/guardian with minor assent for 12 through 17 year olds)

Exclusion Criteria:

  • Progressive malignancy
  • Diagnosis of a hormone responsive malignancy
  • Uncontrolled infection at initiation of protocol treatment
  • Current thromboembolic disease requiring full-dose anticoagulation - patients receiving pharmacologic prophylaxis for thromboembolic disease will be eligible
  • Active or recent (within prior 3 months) thrombus, irrespective of anticoagulation status
  • Pregnancy as assessed on baseline blood hCG level
  • Unwilling or unable to stop supplemental sex hormone therapy (estrogen, progesterone, and/or testosterone preparations)
  • Women or men of childbearing potential unwilling to take adequate precautions to avoid pregnancy from the start of protocol treatment through 28 days after the last treatment

Screening Inclusion Criteria:

  • Pediatric or adult (ages 0-76 years) HCT recipients
  • Suspected high risk GVHD
  • Voluntary written consent (adult or parent/guardian with minor assent for 12 through 17 year olds)

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): NCT02525029


Contacts
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Contact: Timothy Krepski 612-273-2800 tkrepsk1@fairview.org

Locations
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United States, Minnesota
Masonic Cancer Center at University of Minnesota Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Tim Krepski    612-273-2800    tkrepsk1@fairview.org   
Sponsors and Collaborators
Masonic Cancer Center, University of Minnesota
Investigators
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Principal Investigator: Shernan Holtan, MD University of Minnesota - Clinical and Translational Science Institute

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Responsible Party: Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier: NCT02525029     History of Changes
Other Study ID Numbers: 2014LS020
First Posted: August 17, 2015    Key Record Dates
Last Update Posted: December 6, 2018
Last Verified: December 2018
Keywords provided by Masonic Cancer Center, University of Minnesota:
GVHD
Additional relevant MeSH terms:
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Graft vs Host Disease
Immune System Diseases
Chorionic Gonadotropin
Reproductive Control Agents
Physiological Effects of Drugs