Azacitidine, Lenalidomide and DLI as Salvage Therapy for MDS, CMML and sAML Relapsing After Allo-HSCT

• Status: Completed
• Trial end date: 2020-04-23
• Target enrollment: 0
• Participant gender: All

Summary

This is a prospective, open-label, single-arm multi-center phase II study aiming to evaluate the safety and feasibility of the addition of Lenalidomide (investigational drug) to the standard therapy of Azacitidine and DLI (standard of care) as first salvage therapy for relapse of MDS, CMML and AML with MDS-related changes (sAML, with 20%-30% bone marrow blasts, formerly RAEB-T) after allo-SCT. The starting dose of Lenalidomid is 2.5 mg per day for 21 days with a 7 day rest. The study incorporates 2 interim safety analyses after 10 and 20 patients in order to find the optimal and safe dose of Lenalidomide.

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

Details

• Lead Sponsor: Heinrich-Heine University, Duesseldorf
• Collaborator: Celgene Corporation
• Treatments: Azacitidine; Lenalidomide; Thalidomide

Criteria

Inclusion Criteria:

• First relapse of de novo or therapy-related MDS, CMML or AML according to WHO classification (revised version 2016) without FLT3 mutation and without known IDH mutation after first allo-SCT (related or unrelated donor with < 2 HLA mismatches)

• Possibility of DLI (no cord blood, no haploidentical donor)

• no previous therapy for relapse after allo-SCT

• ECOG performance status ≤ 2 at study entry

• no active GvHD treated with systemic immunosuppression within 4 weeks before inclusion

• no uncontrolled infection at inclusion

• Understand and voluntarily sign an informed consent form.

• Age 18 years at the time of signing the informed consent form.

• Able to adhere to the study visit schedule and other protocol requirements.

• All females must acknowledge to have understood the hazards and necessary precautions associated with the use of lenalidomide

Exclusion Criteria:

• Relapse after second allogeneic Transplantation

• AML with FLT3 mutation (ITD or TKD)

• AML with known IDH mutation (IDH1 or IDH2)

• Any previous therapy (chemotherapy, radiation or investigational drugs) administered as therapy for relapse after allo-SCT

• previous transplantation with cord blood, an haploidentical donor or a related/unrelated donor with

≥2 HLA mismatches

• Active GvHD requiring systemic immunosuppression within the last 4 weeks

• Uncontrolled infection

• Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.

• Pregnant or lactating females

• Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study

• Impaired renal function (GFR < 20 ml/min)

• Impaired hepatic function

• Known hypersensitivity to thalidomide, lenalidomide or any components of the treatment

• The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs.

• Concurrent use of other anti-cancer agents or treatments.

• Known positive for HIV or infectious hepatitis, type A, B or C.

• Neuropathy ≥ grade 2

• Prior history of malignancy other than MDS or AML (except basal cell or squamous cell carcinoma or carcinoma in situ of the cervix or breast) unless the subject has been free of disease for ≥ 3 years

• Participation in another study with ongoing use of unlicensed investigational product from 28 days before study enrollment until the end of the study