Azacytidine and Lymphocytes in Relapse of AML or MDS After Allogeneic Stem Cell Transplantation.

NCT02017457 | Completed Phase 2

• 1 other identifier: BHS-TC-10
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 12

Brief Summary

The present project is a multicenter, phase II trial which aims at evaluating if the administration of azacytidine (Vidaza®) combined to donor lymphocyte infusion (DLI) could improve the response rate to DLI in the population of patients with relapsed acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) after allogeneic hematopoietic stem cell transplantation.

Conditions

Acute Myelogenous Leukemia; Myelodysplastic Syndrome

Keywords

Hematology; Acute Myelogenous Leukemia; Myelodysplasic syndrome; Allogeneic stem cell transplantation; Donor lymphocyte infusion; DLI; Azacytidine; Vidaza; Overall response rate; Relapse

Outcome Measures

Primary Outcomes (1)

• Response rate

  To assess the response rate to DLI by the combination with azacytidine in the population of patients with relapsed AML and MDS after allo-SCT.

  Will be evaluated at day 24 of cycle 1, 3 and 5. Then every 3 months for a year after cycle 6 thereafter at 1.5 and 2 years after cycle 6

Secondary Outcomes (5)

• Disease-free survival

  2 years after cycle 6

• Overall survival

  2 years after cycle 6

• Evaluation of the treatment Toxicity

  At the beginning of each cycle and at the discretion of the investigator until cycle 6, then monthly for 6 months, thereafter every 3 months for 1.5 years

• Incidence and severity of GvHD

  At the beginning of each cycle and at the discretion of the investigator until cycle 6, then monthly for 6 months, thereafter every 3 months for 1.5 years

• Incidence and severity of infections

  At the beginning of each cycle and at the discretion of the investigator until cycle 6, then monthly for 6 months, thereafter every 3 months for 1.5 years

Other Outcomes (3)

• Immune reconstitution

  On day 1 of each cycle until cycle 6, then every 3 months for a year and at 1.5 and 2 years after cycle 6

• Immune reconstitution

  On day 1 of each cycle until cycle 6, then every 3 months for a year and at 1.5 and 2 years after cycle 6

• Treg expansion

  On day 1 of each cycle until cycle 6, then every 3 months for a year and at 1.5 and 2 years after cycle 6

Study Arms (1)

Azacytidine + Donor lymphocyte infusion

EXPERIMENTAL

Azacytidine will be administered subcutaneously for 5 days. During the first cycle, a dose of 100mg/m2/day will be used and for the following cycles a dose of 35mg/m2/day will be administered. Each cycle will consist in 28 days. All patients will receive at least 6 cycles of Azacytidine and the total number of cycles will depend on the response to treatment. Donor lymphocyte infusion will be performed on day 1 of cycle 2, 4 and 6 of Azacytidine. The amount of cells infused will depend on donor origin.

Biological: Donor lymphocyte infusion; Drug: Azacytidine

Interventions

Donor lymphocyte infusion BIOLOGICAL

On day 1 of cycle 2, 4 and 6 of Azacytidine, patients will be infused with donor lymphocytes (ideally on day 1 but in case of organizational problems, DLI can be administered until day 5) . * Patients with a sibling donor will receive: * 5x10exp7 CD3+/kg on day 1 of cycle 2 * 5x10exp7 CD3+/kg on day 1 of cycle 4 * 10x10exp7 CD3+/kg on day 1 of cycle 6 * Patients with an unrelated donor will receive: * 1x10exp7 CD3+/kg on day 1 of cycle 2 * 5x10exp7 CD3+/kg on day 1 of cycle 4 * 10x10exp7 CD3+/kg on day 1 of cycle 6

Also known as: DLI

Azacytidine + Donor lymphocyte infusion

Azacytidine DRUG

* Cycle 1: Subcutaneous administration of 100mg/m2/day for 5 days. * Cycle 2: Subcutaneous administration of 35mg/m2/day for 5 days. Cycles will be administered every 28 days. All patients will receive at least 6 cycles of Azacytidine except if progression requests additional disease-related treatment such as hydroxyurea or other chemotherapeutic agents. In such cases, the patient will be excluded from the study and only disease status and survival status will be reported during the 3-year follow-up period. In case of complete remission after cycle 5, 2 additional cycles will be administered after achievement of complete remission. In case of stable disease or partial response, Azacytidine will be continued until progression. In case of disease progression after cycle 6, Azacytidine will be stopped.

Also known as: Vidaza

Azacytidine + Donor lymphocyte infusion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients:
• Age ≥ 18 years
• Be able to understand and sign informed consent
• Fertile patients must use a reliable contraception method
• Disease status at transplantation:
• AML in first or subsequent complete remission (\< 5% marrow blasts)
• MDS with less than 10% marrow blasts at the time of transplantation
• Transplantation:
• Allogeneic transplantation using a sibling or unrelated donor with matching in 10/10 alleles (HLA-A, B, C, DRB1, DQB1) or maximum of one allele or one antigen or 1 antigen + 1 allele or 1 antigen + 1 DQB1 antigen or 2 alleles mismatches.
• Myeloablative or reduced-intensity conditioning
• Second transplantation is allowed
• Donor is willing to donate lymphocytes
• Clinical situation:
• Cytological relapse after allo-SCT defined as the recurrence of more than 5% blasts on bone marrow aspiration (AML) or evidence of MDS
• Immunophenotypic relapse defined as the recurrence of an abnormal phenotype on flow cytometry in bone marrow aspirate (only in case of a specific phenotype).

You may not qualify if:

• Extramedullary relapse including CNS involvement
• ECOG Performance status \> 2
• Uncontrolled infection
• HIV positive
• Acute or chronic heart failure (NYHA class III or IV) or symptomatic ischemic heart disease or ejection fraction \< 35% or uncontrolled arrhythmia
• Severe liver failure (total bilirubin \> 3 mg/dL, SGPT \> 4 X upper normal limit)
• Severe pulmonary failure (corrected DLCo \< 35%)
• Terminal renal failure requiring dialysis
• Severe neurological or psychiatric disorders
• Concurrent investigational drug.
• Female who is pregnant or breastfeeding

Sponsors & Collaborators

• Carlos Graux, MD, PhD: lead
• Celgene Corporation: collaborator
• Belgian Hematological Society: collaborator

Study Sites (12)

Ziekenhuis Netwerk Antwerpen

Antwerp, 2060, Belgium

Location

AZ Sint-Jan Brugge

Bruges, 8000, Belgium

Location

Institut Jules Bordet

Brussels, 1000, Belgium

Location

Universitair Ziekenhuis Antwerpen

Edegem, 2650, Belgium

Location

Universitair Ziekenhuis Gent

Ghent, 9000, Belgium

Location

Hopital de Jolimont

Haine-St-Paul, 7100, Belgium

Location

Universitair Ziekenhuis Brussel

Jette, 1090, Belgium

Location

Universitair Ziekenhuis Leuven

Leuven, 3000, Belgium

Location

CHU Liège

Liège, 4000, Belgium

Location

Hartziekenhuis Roeselare Menen

Roeselare, 8800, Belgium

Location

Cliniques Universitaires Saint-Luc

Woluwe-Saint-Lambert, 1200, Belgium

Location

CHU Mont-Godinne

Yvoir, 5530, Belgium

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Recurrence

Interventions

Azacitidine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Xavier Poiré, MD

  Cliniques universitaires Saint-Luc- Université Catholique de Louvain

  PRINCIPAL INVESTIGATOR

• Carlos Graux, MD, PhD

  Cliniques Universitaires Mont-Godinne

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: December 16, 2013
• First Posted: December 20, 2013
• Study Start: December 1, 2013
• Primary Completion: November 1, 2019
• Study Completion: November 1, 2019
• Last Updated: December 10, 2019

Record last verified: 2019-12

Locations

BE (12)