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

• Status: Completed
• Trial end date: 2019-03-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Universitätsklinikum Hamburg-Eppendorf
• Collaborators: Crolll Gmbh; Novartis
• Treatments: Everolimus; Prednisone; Sirolimus

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