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

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2015 by European Myeloma Network
Information provided by (Responsible Party):
European Myeloma Network Identifier:
First received: September 22, 2011
Last updated: February 25, 2015
Last verified: February 2015

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.

Condition Intervention Phase
Hematologic Malignancies
Multiple Myeloma
Drug: Bz (Bortezomib)
Drug: Len (lenalidomide)
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: European Myeloma Network Sequential Phase I / Phase II Trial on RIC Allogeneic Transplantation: an Optimized Program for High Risk Relapsed Patients

Resource links provided by NLM:

Further study details as provided by European Myeloma Network:

Primary Outcome Measures:
  • 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. [ Time Frame: Up to one year after transplant ] [ Designated as safety issue: Yes ]

    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.

Secondary Outcome Measures:
  • Incidence of GVHD with this combination (phase I and II) [ Time Frame: Up to one year after transplant ] [ Designated as safety issue: Yes ]
    Evaluation of a novel combination of Bz plus Len to prevent GVHD after allogeneic transplantation in patients with haematologic malignancies/MM

  • Phase II: response and relapse rate of this approach [ Time Frame: Up to one year after transplant ] [ Designated as safety issue: Yes ]
    Reduction of relapse rate as defined by the EBMT (European Group for Blood, and Marrow Transplant)criteria.

  • Phase II: safety of the procedure [ Time Frame: Up to one year after transplant ] [ Designated as safety issue: Yes ]
    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).

  • Evaluate the efficacy on survival [ Time Frame: Up to one year after transplant ] [ Designated as safety issue: No ]
    Evaluate the efficacy of the procedure in terms of event free and overall survival

  • Efficacy of positron emission tomography (PET scan)and local radiotherapy [ Time Frame: Up to one year after transplant ] [ Designated as safety issue: No ]
    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

Estimated Enrollment: 45
Study Start Date: November 2011
Estimated Study Completion Date: May 2016
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Drug: Bz (Bortezomib)
Bz 1.3 mg/m2 on days +1, +4 and +7. Maintenance therapy and dose reduction pre-specified.
Other Names:
  • Codenamed PS-341
  • Marketed as Velcade
Drug: 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.

Other Names:
  • Rapamycin
  • CC-5013
  • Marketed as Revlimid


Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01460420

Contact: Jose-Antonio Perez-Simon, MD-PhD 0034955013260
Contact: Clara Rosso, MD 0034955013414

Medizinische Klinik and Poliklinik II, University Hospital Not yet recruiting
Würzburg,, Germany
Contact: Herman Einsele, MD-PhD   
Principal Investigator: Herman Einsele, MD-PhD         
S Giovanni Battista Hospital Recruiting
Torino, Italy
Contact: Benedetto Bruno, MD-PhD   
Principal Investigator: Benedetto Bruno, MD-PhD         
Azienda Ospedaliera Universitaria di Udine Active, not recruiting
Udine, Italy
Hospital Santa Creu I Sant Pau, Recruiting
Barcelona,, Spain
Contact: Miquell Granell, MD-PhD   
Principal Investigator: Miquell Granell, MD-PhD         
Hospital Clinic i Provincial, Recruiting
Barcelona,, Spain
Contact: Laura Rosinol, MD-PhD   
Principal Investigator: Laura Rosinol, MD-PhD         
Sub-Investigator: Joan Bladé, MD-PhD         
Hospital Universitario Ramón y Cajal Recruiting
Madrid, Spain, 28034
Contact: Pilar Herrera, MD.PhD         
Hospital Gregorio Marañón, Recruiting
Madrid, Spain
Contact: Jorge Gayoso, MD-PhD   
Sub-Investigator: Jorge Gayoso, MD-PhD         
Hospital Clinico Universitario Salamanca, Recruiting
Salamanca,, Spain
Contact: Lucía Lopez del Corral, MD-PhD         
Principal Investigator: Lucia López del corral, MD-Phd         
Sub-Investigator: Marivi Mateos, MD-PhD         
Hospital Universitario Virgen del Rocío, Recruiting
Sevilla, Spain
Contact: Jose-Antonio Perez-Simon, MD-PhD   
Principal Investigator: Jose-Antonio Perez-Simon, MD-PhD         
Sub-Investigator: Teresa Caballero, MD-PhD         
Karolinska University Hospital, Huddinge Recruiting
Stockholm, Sweden
Contact: Gösta Gahrton, MD-PhD   
Principal Investigator: Gösta Gahrton, MD-PhD         
Sub-Investigator: Hareth Nahi, MD-PhD         
Sponsors and Collaborators
European Myeloma Network
Principal Investigator: Jose-Antonio Perez-Simon, MD-PhD University Hospital Virgen del Rocio
  More Information

Additional Information:
Responsible Party: European Myeloma Network Identifier: NCT01460420     History of Changes
Other Study ID Numbers: EMN-alloRIC2010 
Study First Received: September 22, 2011
Last Updated: February 25, 2015
Health Authority: Spain: Spanish Agency of Medicines
Italy: The Italian Medicines Agency
Germany: Federal Institute for Drugs and Medical Devices
Sweden: The National Board of Health and Welfare
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by European Myeloma Network:
Allogeneic transplantation
Hematologic malignancies
Multiple myeloma
RIC (Reduced Intensity Conditioning)

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Blood Protein Disorders
Cardiovascular Diseases
Hematologic Diseases
Hemorrhagic Disorders
Hemostatic Disorders
Immune System Diseases
Immunoproliferative Disorders
Lymphoproliferative Disorders
Neoplasms by Histologic Type
Vascular Diseases
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Antineoplastic Agents
Growth Inhibitors
Growth Substances
Immunologic Factors
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses processed this record on May 02, 2016