Len/Dex/DLI in Relapsed Multiple Myeloma After Allogeneic Stem Cell Transplant

May 6, 2026 updated by: Jean Roy, Ciusss de L'Est de l'Île de Montréal

A Phase II, Open-label Study of Lenalidomide and Dexamethasone Followed by Donor Lymphocyte Infusions in Relapsed Multiple Myeloma Following Allogeneic Stem Cell Transplant

Multiple Myeloma (MM) is a morbid disease which can only be cured with an allogeneic hematopoietic stem cell transplant (HSCT). Approximately 50% of allotransplanted patients will relapse, with a median survival of 5 years. Better approaches to improve disease control at relapse, while decreasing toxicity, are urgently needed.

Relapse after allogeneic transplant is a failure of the graft versus MM effect (GvMM). DLIs can be used to control disease following relapse, but the optimal dose, schedule of administration and drug association remain elusive, while the immunosuppression found in MM patients can compromise their effect. One reason for immunotherapy failure relates to the immunological environment: as much as myeloma cells depend on their microenvironment to survive and proliferate, the immunotherapeutic effect of allogeneic HSCT depends on both systemic and local immunological status to be efficacious. Immunomodulatory drugs such as Lenalidomide (Len) have been tried in various settings after allogeneic transplantation with the aim to reverse immunosuppression and stimulate the GvMM, but if and how Len influences a GvMM and thereby promotes an immunotherapeutic success remained uncharacterized. Therefore, a deeper understanding of the immunological environment in MM patients is needed in order to establish and / or restore a potent GvMM effect.

This study proposes the powerful combination of the two following goals, one clinical and one biological :

  1. Clinical: The investigators propose a two-step treatment using first Len in association with Dexamethasone (Dex), followed by Donor Leukocytes Infusions (DLIs) to offer an optimal disease control strategy in relapsed patients. The cytoreductive and immunomodulatory effects of Len is expected to induce a permissive immunological environment for the immunotherapeutic activity of DLIs to develop, while the association with Dex will lessen the risk of graft-versus-host disease (GVHD). This treatment combination has the potential to further improve depth of myeloma response, delay myeloma progression and improve patient survival.
  2. Biological: In an attempt to gain knowledge on how the GvMM behaves in MM patients post-relapse after having received a combined treatment of Len/Dex/DLIs, the investigators propose to characterize the immune environment of their bone marrow (BM) using both minimal residual disease (MRD) assessement by flow cytometry and an unbiased analysis of the transcriptome at various time points.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Myeloma patients in first relapse after sibling or unrelated donor allogeneic transplant willing to participate in this study will be screened for eligibility.

  1. After baseline evaluation including BM aspirate for plasma cell count, minimal residual disease using 8-color multiparameter flow cytometry, transcriptome sequencing and a positron emission tomography (PET scan), patients will receive Len- Dex daily x 21 days with Dex 40 mg once weekly for a total of 6 cycles of 28 days each
  2. Patients will then be evaluated clinically for acute and chronic GVHD before each cycle and a PET scan will be performed at the end of Len/Dex treatment
  3. Sibling and unrelated donor transplant recipients will receive 3 DLIs

  4. Disease and immune evaluation using serum and urine electrophoresis/immunofixation in addition to measurement of serum-free light chains, BM aspirate for plasma cell count and minimal residual disease using 8-color multiparameter flow cytometry, transcriptome sequencing and a PET scan will be performed

    1. A BM aspirate will be performed before each DLI for plasma cell count, MRD evaluation by flow cytometry and transcriptome sequencing
    2. Patients will be followed with a BM aspirate every 3 months x 1 year, then yearly and at progression for plasma cell count and evaluation
    3. Transcriptome sequencing will be done on BM aspirates at time of relapse, after Len/Dex cycles, 6m, 12m, 18m and 24m after the last-DLI.
    4. A PET scan will be performed after the last DLI and at progression.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
10

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Quebec
      • Montreal, Quebec, Canada, H1T2M4
        • CIUSSS de l'Est-de-l'île-de-Montréal, Installation Hôpital Maisonneuve Rosemond

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Age 18-65 years
  2. Myeloma patients in first relapse after a sibling or unrelated allogeneic stem cell transplantation
  3. Patients with measurable disease at time of relapse based on the IMWG criteria
  4. All study participants must comply with the Revlimid Pregnancy Prevention Plan.

  5. Females of reproductive potential must adhere to the scheduled pregnancy testing as required in the Revlimid Pregnancy Prevention Plan.

    Exclusion Criteria:

  6. Relapse occurred within 180 days post allograft
  7. Refractory to Len at any given time before allogeneic transplantation
  8. Presence of ≥ grade II or uncontrolled acute GVHD
  9. Presence of severe or uncontrolled chronic GVHD
  10. Karnofsky score < 70%
  11. Bilirubin > 50 μmol/L unless felt to be related to Gilbert's disease or hemolysis; AST and ALT > 5 x upper limit of normal (ULN); alkaline phosphatase > 5 x ULN
  12. Known hypersensitivity to Len or Dex
  13. Active infection with any of the following viruses: HIV, HTLV-1 or 2, hepatitis B (defined as HBsAg positivity) or hepatitis C (defined as anti-HCV positivity or HCV-RNA positivity)
  14. Presence of another malignancy with an expected survival estimated < 75% at 5 years (complete resection of basal cell carcinoma or squamous cell carcinoma, complete resection of a ductal carcinoma in situ, presence of lobular carcinoma in situ, complete resection of carcinoma in situ of the cervix, or an in situ or low-risk prostate cancer after curative therapy are not exclusion criteria)
  15. Positive beta-human chorionic gonadotropin pregnancy test, to be performed in all women of childbearing potential at screening and baseline. Female study participants who are surgically sterile (hysterectomy) or who have been postmenopausal for at least 12 consecutive months are automatically eligible for this criterion
  16. Females of child-bearing potential not agreeing to remain abstinent or to use 2 simultaneous effective methods of contraception from at least 4 weeks before, to at least 4 weeks following discontinuation of Len. Males not agreeing to use a condom during any sexual contact with females of child-bearing potential from at least 4 weeks before, to at least 4 weeks following discontinuation of Len
  17. Women who are lactating
  18. Female of child-bearing potential who are planning to become pregnant while enrolled in this study up to 4 weeks after the last Len dose
  19. Participation in a trial with an investigational agent within 30 days prior to entry in the study
  20. Inability to provide written informed consent prior to initiation of any study-related procedures, or inability, in the opinion of investigators, to comply with all requirements of the study
  21. Estimated probability to survive less than 6 months after initiation of Len and Dex
  22. Current history of drug and/or alcohol abuse
  23. Any abnormal condition or laboratory result that is considered by investigators capable of altering patient's condition, compliance or study outcome
  24. Any patient who, in the opinion of investigators, should not participate in this study
  25. Having received allogeneic stem cell transplantation in relapse after autologous transplant.
  26. Having received Len therapy after allogeneic transplant, before relapse
  27. Poor organ function defined as either: diffusing capacity of the lung for carbon monoxide corrected for hemoglobin using Dinakara method (DLCOc) < 50%; forced expiratory volume in 1 second < 50%; left ventricular ejection fraction (LVEF) < 40% evaluated by echocardiogram or multi-gated acquisition scan (MUGA); uncontrolled arrhythmia; symptomatic cardiac disease; creatinine clearance < 30 mL/minute; liver cirrhosis

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Lenalidomide-Dexamethasone-DLI

  1. Patients will receive Len (10 mg in the presence of ≤ grade I acute GVHD or absence of chronic GVHD; 5 mg in presence of controlled mild or moderate chronic GVHD) daily x 21 days with Dex 40 mg once weekly for a total of 6 cycles of 28 days each

    1. For grade ≥III non hematologic or grade IV hematologic toxicity, Len can be reduced to 5 mg
    2. In absence of these toxicities, acute GVHD (using Glucksberg modified criteria) or severe chronic GVHD (using NIH criteria), Len dose can be increased by 5 mg per cycle to a maximum of 25 mg
  2. If eligibility is confirmed, sibling and unrelated donor transplant recipients will both receive 3 donor lymphocyte infusions (DLIs) at the following doses: 5 x 106 CD3+/kg; 1 x 107 CD3+/kg; 5 x 107 CD3+/kg
  3. Patient will be followed for 5 years post relapse.
Drug: Lenalidomide-Dexamethasone-DLI
Lenalidomide (Len) and Dexamethasone (Dex) for 6 months followed by three donor lymphocyte infusions (DLIs)

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Efficacy of Len-Dex-DLI in patients with relapsed myeloma measured by progression-free survival
Time Frame: 2 years
To determine the as efficacy of Len and Dex followed by DLIs, measured by progression-free survival at 2 years after the last DLI
2 years

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Overall survival at 2 years
Time Frame: 2 years
Kaplan Meier analysis
2 years
Incidence of grade ≥III non hematologic toxicity and incidence of grade ≥IV hematologic toxicity
Time Frame: 5 years
Patients will be evaluated according to protocol and adverse events will be monitored continuously, documented and collected in database
5 years
Incidence of acute GVHD
Time Frame: 1 years
GVHD will be evaluated according to protocol, documented and collected in database. Analysis will be done by cumulative incidence.
1 years
Incidence of chronic GVHD
Time Frame: 2 years
GVHD will be evaluated according to protocol, documented and collected in database. Analysis will be done by cumulative incidence.
2 years
Maximum grades of acute and chronic GVHD
Time Frame: 2 years
GVHD will be evaluated according to protocol, documented and collected in database
2 years
Response to treatment
Time Frame: 3 years
International Myeloma Working Group (IMWG) response after Len/Dex and after DLIs, best response achieved
3 years
Non-relapse mortality after DLIs
Time Frame: 3 years
Analysis by cumulative incidence
3 years
Incidence of progression at 2 years
Time Frame: 2 years
Kaplan Meier analysis
2 years
Disease status assessment by flow cytometry
Time Frame: 5 years
BM evaluation of minimal residual disease (MRD) by multiparametric flow cytometry (MFC) analysis
5 years
Disease status assessment by PET scan
Time Frame: 5 years
Evaluation of extramedullary disease by positron emission tomography (PET) scan
5 years
Evaluation of quality of life (QoL) during treatment
Time Frame: 5 years
QoL questionnaire will be given to patients according to protocol
5 years
Evaluation of the BM microenvironment by transcriptome analysis before and after treatments
Time Frame: 3 years
Both mononucleated celles and extracellular compartment will be analyzed by RNAseq
3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Ciusss de L'Est de l'Île de Montréal

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Celgene
C3i Center Inc.

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Jean Roy, MD, Ciusss de L'Est de l'Île de Montréal

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 12, 2018

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 27, 2024

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 27, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 15, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 26, 2018

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 29, 2018

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 8, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 6, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • HMR003

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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