Clinical trial NCT01460420: Sequential Trial on Reduced Intensity Conditioning (RIC) Allogeneic Transplantation
Official title: European Myeloma Network Sequential Phase I / Phase II Trial on RIC Allogeneic Transplantation: an Optimized Program for High Risk Relapsed Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Hematologic Malignancies
Multiple Myeloma
Keywords: Allogeneic transplantation
Hematologic malignancies
Multiple myeloma
RIC (Reduced Intensity Conditioning)
Lead sponsor: European Myeloma Network B.V.
Sponsor class: NETWORK
First posted: 2011-10-26
Enrollment: 49
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility 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.

Primary outcomes:
measure: 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.
timeFrame: Up to one year after transplant
Secondary outcomes:
measure: Incidence of GVHD with this combination (phase I and II)
timeFrame: Up to one year after transplant
measure: Phase II: response and relapse rate of this approach
timeFrame: Up to one year after transplant
measure: Phase II: safety of the procedure
timeFrame: Up to one year after transplant
measure: Evaluate the efficacy on survival
timeFrame: Up to one year after transplant
measure: Efficacy of positron emission tomography (PET scan)and local radiotherapy
timeFrame: Up to one year after transplant
Other outcomes:
Locations:
city: Würzburg,
country: Germany
facility: Medizinische Klinik and Poliklinik II, University Hospital
city: Torino
country: Italy
facility: S Giovanni Battista Hospital
city: Udine
country: Italy
facility: Azienda Ospedaliera Universitaria di Udine
city: Barcelona,
country: Spain
facility: Hospital Clinic i Provincial,
city: Barcelona,
country: Spain
facility: Hospital Santa Creu I Sant Pau,
city: Madrid
country: Spain
facility: Hospital Universitario Ramón y Cajal
city: Madrid
country: Spain
facility: Hospital Gregorio Marañón,
city: Salamanca,
country: Spain
facility: Hospital Clinico Universitario Salamanca,
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocío,
city: Stockholm
country: Sweden
facility: Karolinska University Hospital, Huddinge
Study officials:
affiliation: University Hospital Virgen del Rocio
name: Jose-Antonio Perez-Simon, MD-PhD
role: PRINCIPAL_INVESTIGATOR
References: