Treatment of Acute Leukemia Relapse After Allotransplantation

Study Overview
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Brief Summary
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Patients with relapse of acute leukemia often only receive supportive therapy. Our hypothesis is that a combination therapy can stabilize the disease for patients with early relapse after allogeneic stem cell transplantation. The investigators will combine 5-azacitidine 100 mg daily subcutaneously (days 1-3), valproic acid (continuous therapy from day 1), All-trans retinoic acid (days 1-14) and hydroxurea (continuous treatment from day 15 of first cycle. Azacitidine and ATRA can be repeated with 5 weeks intervals, donor leukocyte infusions on day 10 is allowed from the second cycle.

Official Title
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Treatment of Relapsed Acute Leukemia After Allogeneic Stem Cell Transplantation: Disease Stabilization Through Chemotherapy, Immunomodulatory Treatment and Immunotherapy

Conditions
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Acute Myeloid Leukemia

Intervention / Treatment
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* Drug: Combined use of azacitidine, valproic acid, hydroxurea and eventually donor leukocyte infusions.


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: AML relapse within one year after transplantation Blood and marrow sampling being possible Expected survival at least 4 weeks No expected drug interactions Informed consent possible Exclusion Criteria: Intolerance to any study drug Serious kidney or liver disease Informed consent not possible Previous pancreatitis

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Azacitidine, valproic acid, all-trans retinoic acid, hydroxyurea, eventually donor leukocyte infusions | Drug: Combined use of azacitidine, valproic acid, hydroxurea and eventually donor leukocyte infusions.<br>* Azacitidine 100 mg day 1-3 in each cycle Valproic acid, continuous therapy from day 1 All-trans retinoic acid 22.5 mg/m2 twice daily day 1-14 in each cycle Hydroxurea 500 mg initially eventually increased to 1 g daily. Eventually donor leukocyte infusions on day 10 from the second cycle.<br>* Other names: Give as repeated cycles with 5 weeks intervals. Donor leukocyte infusions are allowed from cycle 2.;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease stabilization | Strict criteria defined in the protocol. | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival |  | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute myeloid leukemia, Allogeneic stem cell transplantation, Relapse, Disease stabilization, survival