Lenalidomide-Adriamycin-Dexamethasone (RAD) Induction Followed by Stem Cell Transplant in Newly Diagnosed Multiple Myeloma

Study Overview
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Brief Summary
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Subjects up to the age of 65 years with newly diagnosed multiple myeloma requiring treatment are eligible. Minimal pretreatment (2 cycles of chemotherapy; local irradiation; surgery) is permitted. After enrollment, patients are to receive four cycles of RAD induction treatment: a combination of lenalidomide (Revlimid), adriamycin, and dexamethasone. If at least a minimal response is achieved to RAD, they will undergo chemomobilization (cyclophosphamide, etoposide) of peripheral blood stem cells and one uniform cycle of high-dose melphalan chemotherapy followed by a first stem cell transplant. If any of the high-risk features (such as elevated beta 2-microglobulin, adverse cytogenetic factors, elevated LDH, Ig A isotype) were present at diagnosis, patients will be allocated to a consolidative allogeneic transplant following dose-reduced conditioning. If no appropriate donor is available, the patient does not consent or lacks of high-risk features a second autograft following high-dose melphalan will be delivered. All patients will proceed to lenalidomide maintenance (one year) following hematopoietic reconstitution.

Official Title
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Lenalidomide (Revlimid®), Adriamycin and Dexamethasone (RAD)as an Induction Therapy in Newly Diagnosed Multiple Myeloma Followed by a Risk-Defined Transplant Strategy and Lenalidomide Maintenance - A Multicenter Phase II Trial by Deutsche Studiengruppe Multiples Myeloma (DSMM XII)

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Procedure: allogeneic stem cell transplant versus second autologous transplantation
* Drug: RAD


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent Newly diagnosed multiple myeloma Maximum of one prior systemic therapy (2 cycles) Presence of CRAB criteria Measurable disease parameters Left ventricular ejection fraction at least 55% DLCO of at least 60% Adequate bone marrow function Use of adequate contraception for female subjects with childbearing potential and all male subjects Eligible for autologous and allogeneic stem cell transplantation Bone marrow baseline sample evaluable for interphase cytogenetics Exclusion Criteria: Any serious medical conditions preventing the subject from written informed consent Progressive disease (PD) to any initial treatment Pregnant or lactating females Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data Use of any other experimental drug or therapy within 28 days of baseline Preexisting neuropathy of ≥ grade 2 severity Known hypersensitivity to thalidomide Any prior use of lenalidomide Positive for HIV or infectious hepatitis, type A, B or C after serologic testing Serum creatinine despite induction therapy ≥ 2.0 mg/dL

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Allogeneic stem cell transplant<br>Second scheduled transplantation performed from an HLA-matched MRD or MUD after conditioning with treosulfan and fludarabine | Procedure: allogeneic stem cell transplant versus second autologous transplantation<br>* Transplantation of stem cells from a MRD or MUD, respectively after dose-reduced conditioning versus autologous stem cell graft after preparation with melphalan 200 mg/m²<br>Drug: RAD<br>* After enrollment, patients are to receive four cycles of RAD induction treatment: a combination of lenalidomide (Revlimid), adriamycin, and dexamethasone.<br>|
| Active Comparator: High-dose melphalan chemotherapy<br>Second high-dose melphalan therapy followed by transplantation of peripheral blood stem cells | Procedure: allogeneic stem cell transplant versus second autologous transplantation<br>* Transplantation of stem cells from a MRD or MUD, respectively after dose-reduced conditioning versus autologous stem cell graft after preparation with melphalan 200 mg/m²<br>Drug: RAD<br>* After enrollment, patients are to receive four cycles of RAD induction treatment: a combination of lenalidomide (Revlimid), adriamycin, and dexamethasone.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate to RAD induction and transplant (stringent CR, CR, very good PR) |  | 9 months from start of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival (PFS) |  | 9 months from start of treatment | 
| Incidence and relationship of severe adverse events |  | 1 year from start of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Allogeneic stem cell transplantation, Lenalidomide, IMiD