Lenalidomide-Dexamethasone-DLI for Multiple Myeloma

Recruiting in Palo Alto (17 mi)

Overseen byJean Roy, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Waitlist Available

Sponsor: Ciusss de L'Est de l'Île de Montréal

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?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.

Eligibility Criteria

This trial is for adults aged 18-65 with multiple myeloma in first relapse post-allogeneic stem cell transplant. Participants must not be pregnant, planning pregnancy, or breastfeeding and must follow strict contraception guidelines. They should have measurable disease but no recent participation in other drug trials, no early post-transplant relapse, no Lenalidomide resistance or active severe infections.

Inclusion Criteria

I am between 18 and 65 years old.

My myeloma has returned after my first stem cell transplant.

You have a detectable disease based on specific criteria at the time of a relapse.

+2 more

Exclusion Criteria

Your bilirubin, AST and ALT levels are too high, unless it's due to a condition called Gilbert's disease or hemolysis. Your alkaline phosphatase level is also too high.

I do not have an active infection with HIV, HTLV-1 or 2, hepatitis B, or hepatitis C.

You are currently struggling with drug or alcohol abuse.

+19 more

Participant Groups

The study tests a two-step treatment combining Lenalidomide (Len) and Dexamethasone (Dex), followed by Donor Leukocytes Infusions (DLIs). This aims to control the disease after relapse from stem cell transplant by creating an environment that allows DLIs to work better while reducing the risk of graft-versus-host disease.

1Treatment groups

Experimental Treatment

Group I: Lenalidomide-Dexamethasone-DLIExperimental Treatment1 Intervention

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.

Dexamethasone is already approved in European Union, United States, Canada, Japan for the following indications:

🇪🇺 Approved in European Union as Dexamethasone for: