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

Sponsor

Wuerzburg University Hospital (Other)

Overall Status

Completed

CT.gov ID

NCT00925821

Collaborator

ClinAssess GmbH (Industry), Celgene Corporation (Industry), Amgen (Industry), medac GmbH (Industry)

146

Enrollment

Locations

Arms

12.2

Patients Per Site

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma	Procedure: allogeneic stem cell transplant versus second autologous transplantation Drug: RAD	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

146 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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)

Study Start Date :

Jun 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Allogeneic stem cell transplant 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 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 Drug: RAD After enrollment, patients are to receive four cycles of RAD induction treatment: a combination of lenalidomide (Revlimid), adriamycin, and dexamethasone.
Active Comparator: High-dose melphalan chemotherapy Second high-dose melphalan therapy followed by transplantation of peripheral blood stem cells	Procedure: allogeneic stem cell transplant versus second autologous transplantation 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 Drug: RAD After enrollment, patients are to receive four cycles of RAD induction treatment: a combination of lenalidomide (Revlimid), adriamycin, and dexamethasone.

Arm

Intervention/Treatment

Experimental: Allogeneic stem cell transplant

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

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

Drug: RAD

After enrollment, patients are to receive four cycles of RAD induction treatment: a combination of lenalidomide (Revlimid), adriamycin, and dexamethasone.

Active Comparator: High-dose melphalan chemotherapy

Second high-dose melphalan therapy followed by transplantation of peripheral blood stem cells

Procedure: allogeneic stem cell transplant versus second autologous transplantation

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

Drug: RAD

After enrollment, patients are to receive four cycles of RAD induction treatment: a combination of lenalidomide (Revlimid), adriamycin, and dexamethasone.

Outcome Measures

Primary Outcome Measures

Response rate to RAD induction and transplant (stringent CR, CR, very good PR) [9 months from start of treatment]

Secondary Outcome Measures

Progression-free survival (PFS) [9 months from start of treatment]
Incidence and relationship of severe adverse events [1 year from start of treatment]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Charité University Hospital - Virchow Klinikum	Berlin	Germany
2	Dresden University Hospital	Dresden	Germany	01307
3	Erlangen University Hospital	Erlangen	Germany	91054
4	Freiburg University Hospital	Freiburg	Germany	79106
5	Jena University Hospital	Jena	Germany
6	Kiel University Hospital	Kiel	Germany	24105
7	Munich Grosshadern University Hospital	Munich	Germany	81377
8	University Hospital of Munich Technical University	Munich	Germany	81675
9	Klinikum Nuremberg	Nuremberg	Germany	90419
10	Regensburg University Hospital	Regensburg	Germany	93053
11	Rostock University Hospital	Rostock	Germany	18057
12	Ulm University Hospital	Ulm	Germany	89081