Ignite Creation Date:
2024-05-05 @ 4:44 PM
Last Modification Date:
2024-10-26 @ 9:23 AM
Study NCT ID:
NCT00306813
Status:
COMPLETED
Last Update Posted:
2009-08-04
First Post:
2006-03-15
Brief Title:
Evaluation of Lenalidomide Doxorubicin and Dexamethasone RAD in Patients With Relapsed or Refractory Multiple Myeloma
Sponsor:
University of Wuerzburg
Organization:
University of Wuerzburg
Study Overview
Official Title:
A Multicenter Phase III Trial Evaluating the Safety and Efficacy of Lenalidomide Revlimid CC-5013 in Combination With Doxorubicin and Dexamethasone RAD in Patients With Relapsed or Refractory Multiple Myeloma
Status:
COMPLETED
Status Verified Date:
2006-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This is a multi-center open label uncontrolled non-comparative phase III study in patients with refractory or relapsed multiple myeloma who are eligible for second third or fourth line therapy Patients will be enrolled sequentially into four dose cohorts The feasibility of administrating Revlimid R in combination with Doxorubicin and Dexamethasone AD and the MTD of the combination will be determined in the phase I part of the study Part A When the MTD has been established the efficacy of the combination will be further evaluated in the phase II part of the study Part B
Detailed Description:
Multiple myeloma is an incurable disease that is characterized by the malignant proliferation of plasma cells It is the second most common hematological malignancy is invariable fatal The primary approach for treatment of multiple myeloma is systemic chemotherapy Conventional chemotherapy with melphalan and prednisone MP has increased the survival from 12-17 months to approximately 3 years But several other studies have shown that combination therapy with addition of other agents such as cyclophosphamide nitroureas or anthracyclins does not improve the prognosis of patients with multiple myeloma During the past few years it has been demonstrated that high dose chemotherapy followed by autologous stem cell transplantation can prolong the overall survival of myeloma patients and therefore became the standard of care for younger patients Since it has been demonstrated that high dose chemotherapy is also well tolerated by the elderly high dose chemotherapy is recommended for patients up to an age of about 70 if there is no relevant comorbidity Thus the development of more effective regimens for the teatment of relapsed or refractory myeloma patients is urgently needed Treatment with corticosteroids alone can induce responses in both primarily resistant and relapsed patients with myeloma High pulse dexamethasone 40mg daily d1-4 9-12 and 17-21 showed response rates of 27 in primarily unresponsive patients and 21 in relapsed patients which were initially responsive In combination with anthracyclins like in the VAD-regimen vincristin adriamycin dexamethasoneresponse rates of about 31 were achieved in primary unresponsive patients whereas the response rate was 65 in patients who relapsed but had previously responded to therapy Thus the combination of dexamethasone with anthracyclines and vincristin achieve a certain anti-myeloma activity in relapsed or refractory patients Nevertheless due to the neurotoxicity treatment with vincristin of elderly patients is critical and limited Therefore substitution of vincristine by a less toxic agent with high anti-myeloma activity like the new thalidomide analogues see below could reduce toxicity and improve the therapeutic efficacy of anthracycline and dexamethasone containing regimens Protocol DSMM VII Page 752 29092004 Version 11 dexamethasone containing regimens One interesting drug with substantial anti-myeloma activity in patients with relapsed or refractory myeloma is thalidomide Thalidomide has been demonstrated to induce remissions in about one third of relapsed myeloma patients if given as a single agent therapy Response rates evaluated in phase-II studies could be improved up to 55 if thalidomide was administered in combination with other drugs such as glucocorticoids However substantial side effects were observed such as somnolence constipation and neuropathy These observations led to development of derivatives of thalidomide in order to reduce toxicity and to improve efficacy The thalidomide analogues represent a new class of active drugs based on immunmodulatory and direct anti-myeloma effects which have been demonstrated to have a greater potency to inhibit growth of MM and angiogenesis in vitro and in vivo than thalidomide In a phase I study heavily pretreated patients with relapsed or refractory myeloma were treated with CC-5013 RevlimidTM lenalidomide Revlimid at doses up to 25 mgday was safe and well tolerated The dose-limiting toxicity DLT was myelosupression at a dose level of 50 mgday In contrast to thalidomide treatment with CC- 5013 showed no significant side effects like somnolence constipation or neuropathy In addition 29 of the subjects achieved a 50 paraprotein reduction 71 a reduction of 25 Preliminary phase II data showed in about 20 of relapsed myeloma patients a 50 reduction of paraprotein a 25 reduction could be observed in about 50 No additional toxicity was observed in combination with dexamethasone Thus Revlimid as a single agent is well tolerated and has a profound anti-myeloma activity in patients with refractory or relapsed disease These data suggest that Revlimid combined with chemotherapy could lead to enhanced anti-myeloma effects with acceptable toxicities The present study will investigate the safety and the efficacy of intermittent dosing of CC-5013 Revlimid combined with Dexamethasone and Doxorubicin in the treatment of relapsed or refractory myeloma Objectives Primary Objectives
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None