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Treatment of Newly Diagnosed Moderate or Severe Chronic Graft-versus-host Disease With Prednisone and Everolimus (PredEver first)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01862965
Recruitment Status : Completed
First Posted : May 27, 2013
Last Update Posted : April 2, 2020
Sponsor:
Collaborators:
Novartis
Crolll Gmbh
Information provided by (Responsible Party):
PD Dr. med. Francis Ayuketang Ayuk, Universitätsklinikum Hamburg-Eppendorf

Brief Summary:

In this study patients with moderate to severe chronic graft-versus-host disease will be treated with a combination of prednisone and everolimus. Patients will be treated on the study for a maximum of 12 months and followed up for another 12 months.

The primary hypothesis of this study is that the addition of everolimus to prednisone increases response rates without increasing treatment related mortality or mortality due to relapse of underlying disease.


Condition or disease Intervention/treatment Phase
Chronic Graft-versus-host Disease Drug: PredEver Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 38 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Treatment of Newly Diagnosed Moderate or Severe Chronic Graft-versus-host Disease With Prednisone and Everolimus (PredEver First) - A Prospective Multicenter Phase IIA Study -
Actual Study Start Date : March 6, 2013
Actual Primary Completion Date : February 7, 2018
Actual Study Completion Date : March 2019


Arm Intervention/treatment
Experimental: PredEver
Prednisone and Everolimus
Drug: PredEver
Firstline treatment with prednisone and Everolimus




Primary Outcome Measures :
  1. rate of treatment success [ Time Frame: at 6 months ]
    Patient being alive and having achieved a CR or PR of cGvHD without addition of secondary systemic treatment for cGvHD (see below) and without development of relapse of underlying disease. Addition of any immunosuppressive or immunomodulatory systemic therapy aimed at treating or controlling symptoms of chronic GvHDcGvHD is considered treatment failure. Examples of secondary systemic therapies include (but are not limited to) cyclosporine ACSA, tacrolimus, methotrexate, mycophenolate, rituximab, azathioprine, pentostatine, cyclophosphamid, chloroquine, imatinib, dasatinib, thalidomide, alemtuzumab, etanercept, antithymocyte globulin, infliximab, basiliximab, daclizumab, extracorporeal photopheresis, psoralen with UVA-irradiation (PUVA), pulsed steroid exceeding a dose of 2 mg/kg/day.


Secondary Outcome Measures :
  1. the overall survival rate of patients treated with prednisone and everolimus for chronic GvHDcGvHD [ Time Frame: 1 year ]
  2. time to treatment failure [ Time Frame: average time up to 12 months from start of treatment ]
    To evaluate the time to treatment failure, treatment failure being defined as progression of cGvHD after ≥ 2 weeks in any organ, lack of response (CR/PR) after 12 weeks and/or addition of secondary systemic treatment for cGvHD.

  3. speed of response [ Time Frame: average time up to 12 months from start of treatment ]
    To evaluate the speed of response (time to achievement of CR or PR) of patients treated with prednisone and everolimus for chronic GvHD

  4. Relapse of underlying disease [ Time Frame: 1 year ]
    To evaluate the relapse rate of underlying malignancies of patients treated with prednisone and everolimus

  5. side effects [ Time Frame: 1 year ]
    To assess the side effects of prednisone and everolimus in patients with cGVHD


Other Outcome Measures:
  1. Safety endpoints [ Time Frame: 1 year ]

    All adverse events shall be documented and assessed in this study as described in section 9 below. Particular emphasis will be made on the following:

    • Thrombotic microangiopathy (TMA)
    • Non-infectious pneumonitis (NIP)
    • Avascular osteonecrosis



Information from the National Library of Medicine

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

Inclusion Criteria:

  1. Patient's written informed consent
  2. Women and men capable of reproduction must agree to use adequate contraceptive measures (condom, intrauterine devices, oral contraceptives) until three months after termination of treatment
  3. Age ≥ 18 years
  4. Diagnosis of classic chronic GvHDcGvHD according to NIH criteria [33] and fulfilment of criteria for moderate or severe cGvHD or o Diagnosis of overlap syndrome according to NIH criteria [33] and fulfilment of criteria for moderate or severe cGvHD and ≤ clinical grade 2 of acute GvHD of the gut and no grade 4 acute GvHD of the skin.

NB: A maximum of 30 patients with overlap syndrome will be included in the trial.

Exclusion Criteria:

  1. Late persistent or recurrent acute GvHD without evidence of cGvHD
  2. Relapsed or progressive malignant disease (other than minimal residual disease diagnosed by molecular methods)
  3. Severe uncontrolled infections
  4. Pregnant or lactating women
  5. Inability to tolerate 1 mg/kg prednisone
  6. Inability to take oral medication
  7. Known hypersensitivity to everolimus
  8. History of mTOR- inhibitor associated non-infectious pneumonitis
  9. Participation in another interventional clinical trial with intervention within < 30 days
  10. Prior use of mTOR- inhibitor (everolimus or sirolimus) for treatment of acute GvHD
  11. Prior systemic treatment for chronic GvHD>of cGvHD ≥ 72h
  12. Psychiatric illness that would prevent granting of informed consent
  13. Active viral infection with HIV, hepatitis B or hepatitis C
  14. Severe cardiovascular disease (uncontrolled arrhythmias, congestive heart failure NYHA III or IV, or symptomatic ischemic heart disease)
  15. History of mTOR- inhibitor or CNI-associated TMA that led to discontinuation of mTOR- inhibitor or CNI
  16. Patients with neutrophils < 1000 1,000/µl and / /or platelets < 20.,000/ul µl at time of screening
  17. Donor lymphocyte infusion within the last 30 days
  18. Pre-existing hyperlipidemia prior to treatment with calcineurin inhibitor or mTOR inhibitor
  19. Wound healing complications
  20. Active lymphoma as well as other malignancies
  21. Edema (angioneurotic or peripheral)
  22. Peptic ulcer
  23. Severe colitis ulcerosa
  24. Diverticulitis
  25. Severe osteoporosis
  26. Poorly- controlled hypertension
  27. Glaucoma (angle closure or open angle)
  28. Cornea ulcer or cornea-injuries
  29. Severe diabetes mellitus

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): NCT01862965


Locations
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Germany
Universitätsklinikum Hamburg-Eppendorf
Hamburg, Germany, 20246
Universitätsklinikum Jena
Jena, Germany, 07743
Universitätsmedizin der Johannes Gutenberg-Universität Mainz
Mainz, Germany, 55101
Klinikum der Universität Regensburg
Regensburg, Germany, 93053
Universitätsklinikum Ulm
Ulm, Germany, 89081
Deutsche Klinik fuer Diagnostik GmbH
Wiesbaden, Germany, 65191
Sponsors and Collaborators
Universitätsklinikum Hamburg-Eppendorf
Novartis
Crolll Gmbh
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Responsible Party: PD Dr. med. Francis Ayuketang Ayuk, PD Dr. med., Universitätsklinikum Hamburg-Eppendorf
ClinicalTrials.gov Identifier: NCT01862965    
Other Study ID Numbers: PredEver first
2011-004847-35 ( EudraCT Number )
First Posted: May 27, 2013    Key Record Dates
Last Update Posted: April 2, 2020
Last Verified: April 2020
Keywords provided by PD Dr. med. Francis Ayuketang Ayuk, Universitätsklinikum Hamburg-Eppendorf:
firstline
treatment
prednisone
everolimus
Additional relevant MeSH terms:
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Graft vs Host Disease
Immune System Diseases