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

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)

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.

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