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Sequential Trial on Reduced Intensity Conditioning (RIC) Allogeneic Transplantation (EMN-alloRIC)

5 juli 2017 bijgewerkt door: European Myeloma Network

European Myeloma Network Sequential Phase I / Phase II Trial on RIC Allogeneic Transplantation: an Optimized Program for High Risk Relapsed Patients

The aim of the current study is to improve the outcome of patients with hematologic malignancies (in a phase I trial) and more specifically multiple myeloma (in a phase II trial) by 2 interventions: reduce the risk of graft-versus-host disease (GVHD) and improve the efficacy of the procedure decreasing the risk of relapses after transplant.

Currently, the standard approach used in most centers to prevent graft-versus-host disease after allogeneic transplantation is based on the combination of a calcineurin inhibitor (cyclosporine or tacrolimus) plus a short course of methotrexate. Unfortunately, this strategy is far from ideal, since the risk of acute GVHD is in the range of 30-40% among patients receiving a matched related donor transplantation and even higher among patients receiving transplantation from an unrelated donor while the incidence of chronic GVHD is 60-70% among patients receiving peripheral blood progenitor cells from either a related or unrelated donor.

As far as the patients with multiple myeloma (MM) is concerned, although the development of new drugs has markedly changed the outcome and management of these patients, allogeneic transplantation so far appears to be the only curative option, especially among those patients relapsing after first line treatment. Nevertheless, still new strategies within the allogeneic transplant setting are needed to improve its results.

Relapses may occur either extramedullary (very common in this setting) or systemic. In order to reduce the risk of systemic relapses the investigators will use maintenance therapy with Lenalidomide (Len) which, together with bortezomib (Bz) should contribute to eradicate minimal residual disease (MRD). In case the patient do not obtain complete remission or near complete remission after transplant, in addition to the maintenance therapy, the investigators will use four intensification cycles with VRD (Bz-Len-Dexamethasone).

In summary, the goal is to optimize the efficacy of allogeneic transplantation by two interventions: one focused on reducing the risk of relapse and the other on reducing the incidence of GVHD.

Studie Overzicht

Toestand

Voltooid

Conditie

Interventie / Behandeling

Studietype

Ingrijpend

Inschrijving (Werkelijk)

49

Fase

  • Fase 2
  • Fase 1

Contacten en locaties

In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.

Studie Locaties

  • Duitsland
      • Würzburg,, Duitsland
        • Medizinische Klinik and Poliklinik II, University Hospital
  • Italië
      • Torino, Italië
        • S Giovanni Battista Hospital
      • Udine, Italië
        • Azienda Ospedaliera Universitaria di Udine
  • Spanje
      • Barcelona,, Spanje
        • Hospital Clinic i Provincial,
      • Barcelona,, Spanje
        • Hospital Santa Creu I Sant Pau,
      • Madrid, Spanje, 28034
        • Hospital Universitario Ramon y Cajal
      • Madrid, Spanje
        • Hospital Gregorio Marañón,
      • Salamanca,, Spanje
        • Hospital Clinico Universitario Salamanca,
      • Sevilla, Spanje
        • Hospital Universitario Virgen del Rocío,
  • Zweden
      • Stockholm, Zweden
        • Karolinska University Hospital, Huddinge

Deelname Criteria

Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.

Geschiktheidscriteria

Leeftijden die in aanmerking komen voor studie

18 jaar tot 70 jaar (Volwassen, Oudere volwassene)

Accepteert gezonde vrijwilligers

Nee

Geslachten die in aanmerking komen voor studie

Allemaal

Beschrijving

Inclusion Criteria:

Phase I: For the first 10 patients:

  • Patients with any haematological malignancy in > CR1 (first complete remission)
  • Suitable related donor human leukocyte antigen (HLA)identical
  • Age > 18 and < 70 years

For the 10 subsequent patients:

  • Patients with any haematological malignancy candidates to receive an allogeneic transplant
  • Suitable related or unrelated donor (a maximum of 1 mismatched is allowed)
  • Age > 18 and < 70 years phase II trial:
  • High-risk multiple myeloma patients at first relapse / second complete remission candidates to receive an allogeneic transplantation
  • Age:> 18 < 70 years.
  • Suitable donor, related or unrelated (a maximum of 1 mismatched is allowed)
  • Measurable disease
  • High risk first relapse is defined as:
  • First early relapse after Autologous Stem Cell Transplant (ASCT)< 24 months
  • First late relapses in case the patient does not achieve CR after second ASCT
  • First relapse in patients with poor cytogenetic features
  • All subjects must be able to comply with the Lenalidomide Pregnancy Prevention Risk Management Plan.

Exclusion Criteria:

Any of the following:

  • Prior severe comorbidity such as:

    • Heart failure or previous infarction
    • Uncontrolled Hypertension
    • Arrhythmia
    • Cirrhosis
  • Peripheral neuropathy >Grade 2, 14 days prior to inclusion
  • Psychiatric disease
  • Prior history of other neoplasia except for carcinoma in situ in the last 10 years
  • Hypersensitivity to Bz, Boric acid mannitol.
  • Patients unable to use appropriate contraceptive methods
  • Patients who have received an investigational drug 30 days prior to inclusion
  • Positive human immunodeficiency virus (HIV) or active viral hepatitis
  • Patients with pericardial disease
  • Patients with acute diffuse infiltrative pulmonary disease
  • Patients not willing to comply with the Lenalidomide Pregnancy Prevention Risk Management Plan
  • Patients not willing to receive thromboprophylaxis during the consolidation phase will not be eligible.

Studie plan

Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.

Hoe is de studie opgezet?

Ontwerpdetails

  • Primair doel: Behandeling
  • Toewijzing: NVT
  • Interventioneel model: Opdracht voor een enkele groep
  • Masker: Geen (open label)

Wapens en interventies

Deelnemersgroep / Arm
Interventie / Behandeling
Experimenteel: Bortezomib + Lenalidomide
After conditioning treatment and graft versus host disease prophylaxis with Bz 1.3 mg/m2 on days +1, +4 and +7 plus sirolimus/rapamycin at a dose of 6 mg po on day -5 and then 4 mg per day in order to maintain serum levels in the range of 6-12 ng /mL, a maintenance therapy with Bz 1.3 mg/m2 on days 1, 8 and 15 in cycles of 56 days up to 6 cycles post-transplant and on day +180 Len will be started at a dose of 5 mg and will be maintained until relapse.
Geneesmiddel: Bz (Bortezomib)
Bz 1.3 mg/m2 on days +1, +4 and +7. Maintenance therapy and dose reduction pre-specified.
Andere namen:
  • Codenamed PS-341
  • Marketed as Velcade
Geneesmiddel: Len (lenalidomide)

Len at a dose of 6 mg po on day -5 and then 4 mg per day in order to maintain serum levels in the range of 6-12 ng /mL.

Maintenance therapy and dose reduction pre-specified.

Andere namen:
  • CC-5013
  • Rapamycine
  • Marketed as Revlimid

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Phase I trial: Safety of Len + Bz in patients with hematologic malignancies Phase II trial: Safety and efficacy of an optimized strategy of allogeneic transplantation in multiple myeloma undergoing allogeneic transplantation.
Tijdsspanne: Up to one year after transplant

For phase I trial: safety of Len + Bz. The phase I trial safety criteria will be evaluated in terms of (1) engraftment defined as > 500 granulocytes / microL and > 20.000 platelets / microL x 3 consecutive days will be required for 9/10 patients, (2) incidence of neuropathy grades 3-4 attributed to Bz > 20% (3) incidence of gastrointestinal toxicity attributed to Bz > 20%.

For phase II trial: safety evaluated through adverse events and toxicity and efficacy evaluated as reduction of relapse rate as defined by the EBMT criteria.
Up to one year after transplant

Secundaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Incidence of GVHD with this combination (phase I and II)
Tijdsspanne: Up to one year after transplant
Evaluation of a novel combination of Bz plus Len to prevent GVHD after allogeneic transplantation in patients with haematologic malignancies/MM
Up to one year after transplant
Phase II: response and relapse rate of this approach
Tijdsspanne: Up to one year after transplant
Reduction of relapse rate as defined by the EBMT (European Group for Blood, and Marrow Transplant)criteria.
Up to one year after transplant
Phase II: safety of the procedure
Tijdsspanne: Up to one year after transplant
For all patients safety will be assessed by the reporting of adverse events starting with the first study-related procedure and up to 30 days after the treatment period. The severity of adverse events will be assessed using National Cancer Institute (NCI) common toxicity criteria (CTC).
Up to one year after transplant
Evaluate the efficacy on survival
Tijdsspanne: Up to one year after transplant
Evaluate the efficacy of the procedure in terms of event free and overall survival
Up to one year after transplant
Efficacy of positron emission tomography (PET scan)and local radiotherapy
Tijdsspanne: Up to one year after transplant
Analyze the prognostic value and efficacy of imaging studies using PET scan and local radiotherapy in involved fields prior to or after (> 100 days) conditioning
Up to one year after transplant

Medewerkers en onderzoekers

Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.

Sponsor

European Myeloma Network

Onderzoekers

  • Hoofdonderzoeker: Jose-Antonio Perez-Simon, MD-PhD, University Hospital Virgen del Rocio

Studie record data

Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.

Bestudeer belangrijke data

Studie start

1 november 2011

Primaire voltooiing (Werkelijk)

1 juni 2017

Studie voltooiing (Werkelijk)

29 juni 2017

Studieregistratiedata

Eerst ingediend

22 september 2011

Eerst ingediend dat voldeed aan de QC-criteria

25 oktober 2011

Eerst geplaatst (Schatting)

26 oktober 2011

Updates van studierecords

Laatste update geplaatst (Werkelijk)

6 juli 2017

Laatste update ingediend die voldeed aan QC-criteria

5 juli 2017

Laatst geverifieerd

1 juli 2017

Meer informatie

Termen gerelateerd aan deze studie

Trefwoorden

Aanvullende relevante MeSH-voorwaarden

Andere studie-ID-nummers

  • EMN-alloRIC2010

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