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

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ClinicalTrials.gov Identifier: NCT01460420
Recruitment Status : Completed
First Posted : October 26, 2011
Last Update Posted : July 6, 2017
Sponsor:
Information provided by (Responsible Party):
European Myeloma Network

Tracking Information
First Submitted Date  ICMJE September 22, 2011
First Posted Date  ICMJE October 26, 2011
Last Update Posted Date July 6, 2017
Study Start Date  ICMJE November 2011
Actual Primary Completion Date June 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 22, 2013)
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 ]
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.
Original Primary Outcome Measures  ICMJE
 (submitted: October 25, 2011)
  • Phase I trial: Safety of Len + Bz in patients with hematologic malignancies undergoing allogeneic transplantation. [ Time Frame: 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%.
  • Phase II trial: Safety and efficacy of an optimized strategy of allogeneic transplantation in multiple myeloma [ Time Frame: Up to one year after transplant ]
    For phase II trial: safety evaluated throught adeverse events and toxicity and eficacy evaluated as reduction of relapse rate as defined by the EBMT criteria.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 22, 2013)
  • Incidence of GVHD with this combination (phase I and II) [ Time Frame: 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
  • Phase II: response and relapse rate of this approach [ Time Frame: Up to one year after transplant ]
    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 ]
    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 ]
    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 ]
    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
Original Secondary Outcome Measures  ICMJE
 (submitted: October 25, 2011)
  • Incidence of GVHD with this combination (phase I and II) [ Time Frame: 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
  • Phase II: response and relapse rate of this approach [ Time Frame: Up to one year after transplant ]
    reduction of relapse rate as defined by the EBMT criteria.
  • Phase II: safety of the procedure [ Time Frame: 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).
  • Evaluate the efficacy on survival [ Time Frame: Up to one year after transplant ]
    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 ]
    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
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Sequential Trial on Reduced Intensity Conditioning (RIC) Allogeneic Transplantation
Official Title  ICMJE European Myeloma Network Sequential Phase I / Phase II Trial on RIC Allogeneic Transplantation: an Optimized Program for High Risk Relapsed Patients
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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Hematologic Malignancies
  • Multiple Myeloma
Intervention  ICMJE
  • 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
Study Arms  ICMJE 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.
Interventions:
  • Drug: Bz (Bortezomib)
  • Drug: Len (lenalidomide)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 5, 2017)
49
Original Estimated Enrollment  ICMJE
 (submitted: October 25, 2011)
45
Actual Study Completion Date  ICMJE June 29, 2017
Actual Primary Completion Date June 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Germany,   Italy,   Spain,   Sweden
Removed Location Countries United Kingdom
 
Administrative Information
NCT Number  ICMJE NCT01460420
Other Study ID Numbers  ICMJE EMN-alloRIC2010
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party European Myeloma Network
Study Sponsor  ICMJE European Myeloma Network
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Jose-Antonio Perez-Simon, MD-PhD University Hospital Virgen del Rocio
PRS Account European Myeloma Network
Verification Date July 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP