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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
European Myeloma Network
ClinicalTrials.gov Identifier:
NCT01460420
First received: September 22, 2011
Last updated: January 22, 2013
Last verified: January 2013
  Purpose

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: November 2015
Estimated Primary Completion Date: November 2014 (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

  Eligibility

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

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 ClinicalTrials.gov identifier: NCT01460420

Locations
Germany
University Hospital Dresden, Germany
Dresden, Germany
Freiburg University Medical Center,
Freiburg, Germany
University Medical Center Hamburg-Eppendorf
Hamburg, Germany
Medizinische Klinik and Poliklinik II, University Hospital
Würzburg,, Germany
Italy
S Giovanni Battista Hospital
Torino, Italy
Azienda Ospedaliera Universitaria di Udine
Udine, Italy
Spain
Hospital Santa Creu I Sant Pau,
Barcelona,, Spain
Hospital Clinic i Provincial,
Barcelona,, Spain
Hospital Gregorio Marañón,
Madrid, Spain
Hospital Clinico Universitario Salamanca,
Salamanca,, Spain
Hospital Universitario Virgen del Rocío,
Sevilla, Spain
Sweden
Karolinska University Hospital, Huddinge
Stockholm, Sweden
United Kingdom
Institute of Cancer Research,
London,, United Kingdom
Sponsors and Collaborators
European Myeloma Network
Investigators
Principal Investigator: Jose-Antonio Perez-Simon, MD-PhD University Hospital Virgen del Rocio
  More Information

Additional Information:
No publications provided

Responsible Party: European Myeloma Network
ClinicalTrials.gov Identifier: NCT01460420     History of Changes
Other Study ID Numbers: EMN-alloRIC2010
Study First Received: September 22, 2011
Last Updated: January 22, 2013
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:
Neoplasms
Multiple Myeloma
Neoplasms, Plasma Cell
Hematologic Neoplasms
Neoplasms by Histologic Type
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Neoplasms by Site
Sirolimus
Bortezomib
Lenalidomide
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Angiogenesis Inhibitors

ClinicalTrials.gov processed this record on September 14, 2014