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Acute Myelogenous LeukemiaPhase 2NCT02017457

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

A Phase 2 study testing Donor lymphocyte infusion and Azacytidine in people with Acute Myelogenous Leukemia and Myelodysplastic Syndrome, run by Carlos Graux, MD, PhD at 12 sites in Belgium.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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)… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Donor lymphocyte infusion and Azacytidine
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
50 participants
Where
12 sitesBelgium
Study dates
Dec 2013to Nov 2019
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)
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  • 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).
  • Cytogenetic or molecular relapse defined as the persistence or recurrence of a cytogenetic abnormality or molecular marker in bone marrow aspiration or peripheral blood. WT1 expression is not considered as reliable marker for relapse in this protocol but FLT3-ITD, NPM1, CEBPA, or translocation-specific markers (such as MLL-PTD, AML-ETO, CBFB-MYH11) are.
  • Immunosuppressive therapy should have been stopped before inclusion.

Who cannot join

  • More than 30% marrow blasts at the time of inclusion
  • Extramedullary relapse including CNS involvement
  • ECOG Performance status > 2
  • Active acute grade II-IV GvHD at the time of inclusion
  • Active chronic GvHD requiring systemic therapy at the time of inclusion
  • Uncontrolled infection
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  • 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.
  • Other treatment for relapse, except for hydroxyurea but it should be stopped before inclusion in the study.
  • Female who is pregnant or breastfeeding

Trial locations and contacts

12 sites in 1 country.

12 sites in 1 country

Belgium12 sites

  • Ziekenhuis Netwerk Antwerpen

    Antwerp, 2060

  • AZ Sint-Jan Brugge

    Bruges, 8000

  • Institut Jules Bordet

    Brussels, 1000

  • Universitair Ziekenhuis Antwerpen

    Edegem, 2650

  • Universitair Ziekenhuis Gent

    Ghent, 9000

  • Hopital de Jolimont

    Haine-St-Paul, 7100

  • Universitair Ziekenhuis Brussel

    Jette, 1090

  • Universitair Ziekenhuis Leuven

    Leuven, 3000

  • CHU Liège

    Liège, 4000

  • Hartziekenhuis Roeselare Menen

    Roeselare, 8800

  • Cliniques Universitaires Saint-Luc

    Woluwe-Saint-Lambert, 1200

  • CHU Mont-Godinne

    Yvoir, 5530

Other trials in Belgium

About this study

Official title: Sequential Administration of 5-azacytidine (AZA) and Donor Lymphocyte Infusion (DLI) for Patients With Acute Myelogenous Leukemia (AML) and Myelodysplastic Syndrome (MDS) in Relapse After Allogeneic Stem Cell Transplantation.

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.

Read the detailed description

This is a prospective, multicenter, non-randomized phase II study. The 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.

Because the investigators focus our interest on relapsed MDS and low marrow blast count relapsed AML, the investigators postulate that one cycle at higher doses of azacytidine given at 100 mg/m² during 5 days is enough to induce temporary disease control, as suggested by the predictive value of the immediate response rate after the first cycle described in the study of Czibere et al. Starting with cycle 2, the investigators propose to administer DLI along with azacytidine to optimise the immunomodulatory effect. Because these immunomodulatory effects have been described at low dose, the investigators postulate that 35 mg/m² given during 5 days is enough to harness a graft-versus-leukemia effect and induce durable remissions without exacerbating GvHD. DLI will be given every other cycle following an escalated-dose regimen.

The investigators have estimated a sample size of 50 patients to be recruited during 4 years with a 2-year follow-up and a 3-year long-term follow-up. The whole study will be completed within 9 years.

Being tested
Donor lymphocyte infusion, Azacytidine
Keywords
Hematology, Acute Myelogenous Leukemia, Myelodysplasic syndrome, Allogeneic stem cell transplantation, Donor lymphocyte infusion, DLI, Azacytidine, Vidaza, Overall response rate, Relapse
Medical subject headings
Leukemia, Myeloid, Acute, Myelodysplastic Syndromes, Recurrence

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Donor lymphocyte infusionBiological

    Also called DLI

    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

  • AzacytidineDrug

    Also called Vidaza

    • 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.

Study groups in NCT02017457
Study groupRoleWhat they receive
Azacytidine + Donor lymphocyte infusionExperimentalAzacytidine 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.
Receives: Biological: Donor lymphocyte infusion; Drug: Azacytidine

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 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)

  1. Disease-free survival

    Disease-free survival of patients

    Measured: 2 years after cycle 6

  2. Overall survival

    Overall survival of patients

    Measured: 2 years after cycle 6

  3. Evaluation of the treatment Toxicity

    Evaluate haematological and non-haematological toxicities and safety of the planned therapy.

    Measured: 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

  4. Incidence and severity of GvHD

    Incidence and severity of GvHD

    Measured: 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

  5. Incidence and severity of infections

    Incidence and severity of infections

    Measured: 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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Dec 2013 (estimated)
  2. Study startDec 2013
  3. Primary completionNov 2019
  4. Study completionNov 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
50 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02017457
Sponsor's protocol ID
BHS-TC-10
Status last verified
Dec 2019
First submitted
16 Dec 2013
Last updated
10 Dec 2019
Results posted
No
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Donor lymphocyte infusion and Azacytidine in people with Acute Myelogenous Leukemia and Myelodysplastic Syndrome, run by Carlos Graux, MD, PhD at 12 sites in Belgium.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 17 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 10 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 12 sites in Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Response rate (time frame: 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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02017457.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Dec 2019.

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