Sequential Trial on Reduced Intensity Conditioning (RIC) Allogeneic Transplantation

NCT ID: NCT01460420

Last Updated: 2017-07-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 49 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-11-30
• Study Completion Date: 2017-06-29

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.

Conditions

Hematologic Malignancies; Multiple Myeloma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Bz (Bortezomib)

Intervention Type: DRUG

Bz 1.3 mg/m2 on days +1, +4 and +7. Maintenance therapy and dose reduction pre-specified.

Len (lenalidomide)

Intervention Type: DRUG

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.

Interventions

Bz (Bortezomib)

Bz 1.3 mg/m2 on days +1, +4 and +7. Maintenance therapy and dose reduction pre-specified.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

Codenamed PS-341; Marketed as Velcade; Rapamycin; CC-5013; Marketed as Revlimid

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

European Myeloma Network B.V.

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jose-Antonio Perez-Simon, MD-PhD

Role: PRINCIPAL_INVESTIGATOR

University Hospital Virgen del Rocio

Locations

Medizinische Klinik and Poliklinik II, University Hospital

Würzburg, , Germany

S Giovanni Battista Hospital

Torino, , Italy

Azienda Ospedaliera Universitaria di Udine

Udine, , Italy

Hospital Clinic i Provincial,

Barcelona, , Spain

Hospital Santa Creu I Sant Pau,

Barcelona, , Spain

Hospital Universitario Ramón y Cajal

Madrid, , Spain

Hospital Gregorio Marañón,

Madrid, , Spain

Hospital Clinico Universitario Salamanca,

Salamanca, , Spain

Hospital Universitario Virgen del Rocío,

Seville, , Spain

Karolinska University Hospital, Huddinge

Stockholm, , Sweden

Countries

Germany; Italy; Spain; Sweden

Other Identifiers

EMN-alloRIC2010

Identifier Type: -

Identifier Source: org_study_id