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PhaseII,Open-label,Pilot Study Evaluating the Safety+Efficacy of Certican ® in the Prevention of Chronic Graft-versus-host Disease+Late Pulmonary Complications After Allogeneic Hematopoietic Cell Transplantation Blood

Primary Purpose

Condition After Allogenic Peripheral Stem Cell Transplantation (SCT)

Status

Completed

Phase

Phase 2

Locations

Germany

Study Type

Interventional

Intervention

Everolimus

About this trial

This is an interventional treatment trial for Condition After Allogenic Peripheral Stem Cell Transplantation (SCT)

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Patients after allogeneic stem cell transplantation aged ≥ 18 years
Prophylaxes of GvHD with calcineurin inhibitors (Ciclosporine A, Tacrolimus) and MTX or MMF (previous therapy of acute GvHD with additional prednisone is permitted)
Increased risk of chronic GvHD, defined by
Male with female donor
HLA mismatch class I- or II towards GvHD
Persistant active acute GvHD on day +50 after stem cell transplantation despite of high-dose steroids and cyclosporine
Reduction of baseline FEV1 or DLCO (examined 0 - 50 days before transplantation) of ≥ 25%
New occurrence of acute GvHD between day +50 and +100 after stem cell transplantation
Informed concent

Exclusion Criteria:

Use (prophylactic or therapeutic) of mTor inhibitors after SCT
Overlap of acute and chronic GvHD
Total cholesterol ≥ 3-fold of upper limit (UL) or triglycerides ≥ 3-fold UL
GOT, GPT, Bilirubin ≥ 3-fold UL (if not related to GvHD)
Creatinine ≥ 3-fold UL
Confirmed active hepatitis B or C
All circumstances where impaired wound healing might be a risk factor, esp. surgical interventions in the last weeks, ulcers of skin or mucosa
Known intolerance to Everolimus, Sirolimus or other compoments of Certican®
Lactose intolerance
Pregnancy or lactation
Women in reproductive age, except of women with the following criteria:
Postmenopausal (12 month natural amenorrhea)
Postoperativ (≥ 6 months after bilateral ovariectomy with / without hysterectomy)
During therapy and at least 6 months after the last application of Everolimus: regular and correct high-effective contraception (Pearl-Index < 1; e. g. oral contraception, intrauterine device, implantate, contraceptive patch, combination of barrier methods (condom and cervical cap/diaphragm), abstinence
Men, not using one of the following methods of contraception during therapy and at least 6 month after the last application of Everolimus:
Sexual abstinence
Vasectomy
Condom
Impairments or diseases reducing the ability of informed consent
Participation of another study (e.g. for prophylactic immunsuppression in the stem cell transplantation procedure) within the last 60 day before recruitment

Sites / Locations

Zentrum für Knochenmark- und Blutstammzelltransplantation,

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Everolimus

Arm Description

All patients will be given everolimus and the magnitude of the side effects will be measured

Outcomes

Primary Outcome Measures

Frequency of early withdrawal of treatment within the first 6 weeks on Everolimus

Primary endpoint Frequency of early withdrawal of treatment within the first 6 weeks on Everolimus Reasons for withdrawal of Everolimus treatment: Unacceptabel toxicity Therapy failure: Recurrence of moderate or severe chronic GvHD (according to NIH criteria), clearly differentiated from acute forms of GvHD Reduction of LFS of more than 25% compared to the last value within 14 days before Everolimus treatment Therapy with immunosuppressive drugs in addition to Everolimus

Secondary Outcome Measures

Adverse drug reactions on Everolimus

Adverse drug reactions on Everolimus Frequency and grading of GvHD (according to NIH concerns) and POLT Lung function score (LFS) Overall survival

Full Information

NCT ID

NCT01509560

First Posted

January 3, 2012

Last Updated

February 20, 2017

Sponsor

Gesellschaft fur Medizinische Innovation - Hamatologie und Onkologie mbH

Collaborators

Deutsche Klinik fuer Diagnostik, ClinAssess GmbH

1. Study Identification

Unique Protocol Identification Number

NCT01509560

Brief Title

PhaseII,Open-label,Pilot Study Evaluating the Safety+Efficacy of Certican ® in the Prevention of Chronic Graft-versus-host Disease+Late Pulmonary Complications After Allogeneic Hematopoietic Cell Transplantation Blood

Official Title

Study Type

Interventional

2. Study Status

Record Verification Date

February 2017

Overall Recruitment Status

Completed

Study Start Date

November 1, 2011 (Actual)

Primary Completion Date

April 30, 2016 (Actual)

Study Completion Date

April 30, 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Gesellschaft fur Medizinische Innovation - Hamatologie und Onkologie mbH

Collaborators

Deutsche Klinik fuer Diagnostik, ClinAssess GmbH

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

In this prospective study is to examine whether the use of everolimus in patients after allogeneic SCT as part of GVHD prophylaxis for a further review in clinical studies is appropriate.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Condition After Allogenic Peripheral Stem Cell Transplantation (SCT)

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

21 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Everolimus

Arm Type

Experimental

Arm Description

All patients will be given everolimus and the magnitude of the side effects will be measured

Intervention Type

Drug

Intervention Name(s)

Everolimus

Other Intervention Name(s)

Everolimus: Certican®

Intervention Description

Start therapy: 2x 0.75 mg/day (morning and evening) to receive a serum trough level of 3 - 5 ng/ml. First evaluation of Everolimus serum level 3-7 days after start of therapy, second 7 days later, subsequently on study weeks 4, 6, 9, 12 and 16. Dose has to be adapted if trough level exceeds 5 ng/ml. As soon as Everolimus trough level exceeds 3 ng/ml after start of therapy, calineurine inhibitors (e.g. cyclosporine) will be reduced: halve of the dose for the 3 consecutive days, withdrawal on day 4. Prednisone will be reduced accordingly (a 22 weeks scheme is recommended) Everolimus will be used for 98 days or 14 weeks, as described above Everolimus therapy might be extended (independently of the study) if the patient suffering from milde chronic GvHD (according to NIH criteria) or milde PTOLD and lung function score is not reduced more than 25% since begin of Everolimus therapy Everolimus will be reduced to 50% of the dosage for 2 weeks before withdraw (normally weeks 15 and 16

Primary Outcome Measure Information:

Title

Frequency of early withdrawal of treatment within the first 6 weeks on Everolimus

Description

Time Frame

16 months

Secondary Outcome Measure Information:

Title

Adverse drug reactions on Everolimus

Description

Adverse drug reactions on Everolimus Frequency and grading of GvHD (according to NIH concerns) and POLT Lung function score (LFS) Overall survival

Time Frame

16 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Patients after allogeneic stem cell transplantation aged ≥ 18 years Prophylaxes of GvHD with calcineurin inhibitors (Ciclosporine A, Tacrolimus) and MTX or MMF (previous therapy of acute GvHD with additional prednisone is permitted) Increased risk of chronic GvHD, defined by Male with female donor HLA mismatch class I- or II towards GvHD Persistant active acute GvHD on day +50 after stem cell transplantation despite of high-dose steroids and cyclosporine Reduction of baseline FEV1 or DLCO (examined 0 - 50 days before transplantation) of ≥ 25% New occurrence of acute GvHD between day +50 and +100 after stem cell transplantation Informed concent Exclusion Criteria: Use (prophylactic or therapeutic) of mTor inhibitors after SCT Overlap of acute and chronic GvHD Total cholesterol ≥ 3-fold of upper limit (UL) or triglycerides ≥ 3-fold UL GOT, GPT, Bilirubin ≥ 3-fold UL (if not related to GvHD) Creatinine ≥ 3-fold UL Confirmed active hepatitis B or C All circumstances where impaired wound healing might be a risk factor, esp. surgical interventions in the last weeks, ulcers of skin or mucosa Known intolerance to Everolimus, Sirolimus or other compoments of Certican® Lactose intolerance Pregnancy or lactation Women in reproductive age, except of women with the following criteria: Postmenopausal (12 month natural amenorrhea) Postoperativ (≥ 6 months after bilateral ovariectomy with / without hysterectomy) During therapy and at least 6 months after the last application of Everolimus: regular and correct high-effective contraception (Pearl-Index < 1; e. g. oral contraception, intrauterine device, implantate, contraceptive patch, combination of barrier methods (condom and cervical cap/diaphragm), abstinence Men, not using one of the following methods of contraception during therapy and at least 6 month after the last application of Everolimus: Sexual abstinence Vasectomy Condom Impairments or diseases reducing the ability of informed consent Participation of another study (e.g. for prophylactic immunsuppression in the stem cell transplantation procedure) within the last 60 day before recruitment

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Michael Schleuning, Prof. Dr. med.

Organizational Affiliation

Stiftung Deutsche Klinik für Diagnostik GmbH

Official's Role

Principal Investigator

Facility Information:

Facility Name

Zentrum für Knochenmark- und Blutstammzelltransplantation,

City

Wiesbaden

State/Province

Hessen

ZIP/Postal Code

65191

Country

Germany

12. IPD Sharing Statement

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