Clinical trial NCT00538824
Conditions: Multiple Myeloma
Keywords: myeloma relapsed or refractory multiple myeloma
Sponsor: Weill Medical College of Cornell University
Start date: 2007-12-01; Completion date: 2010-09-22
Enrollment: 5 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
Study Objectives

1. To evaluate the efficacy of the combination of dexamethasone (Decadron®), thalidomide (Thalomid®), and lenalidomide (Revlimid®) as therapy for patients with relapsed or refractory multiple myeloma (MM) who have failed prior treatment with both lenalidomide and thalidomide when used as monotherapies.
2. To evaluate the safety of the combination of lenalidomide, dexamethasone, and thalidomide as a therapy for patients with relapsed or refractory multiple myeloma.

Detailed description:
This phase II study is a treatment program for patients with relapsed or refractory multiple myeloma who have had prior treatment with both thalidomide and lenalidomide in separate regimens each used as a single agent or in combination with corticosteroids. Up to 45 patients will be enrolled. Patients who sign informed consent form and RevAssist® and S.T.E.P.S® patient agreement form and fulfill all eligibility criteria will be enrolled.

DexTR therapy:

Cycles 1-4

* Dexamethasone (40mg ) will be given on days 1-4, 9-12, 17-20 of a 28-day cycle.
* Thalidomide will be given 50mg daily on days 1-7, thereafter 100mg daily on days 8-28 of the first 28-day cycle. Thalidomide will then be given at 100mg/daily for days 1-28 of each subsequent cycle.
* Lenalidomide will be given 25mg daily for days 1-21 of each 28 day cycle.
* Prophylactic medications, such as medications for thrombosis risk, will be given.

After completing 4 cycles:

* Patients who demonstrate disease progression at any time will be taken off study.
* Patients who achieve a resolution of monoclonal gammopathy as detected on serum immunofixation or achieve a plateau of disease (no change in M-spike as detected on serum protein electrophoresis) for \> 2 cycles will be transitioned to maintenance therapy.
* Patients who continue to respond without achieving either a plateau or a CR will continue on induction therapy until plateau for \>2 cycles or CR in the absence of untoward toxicity. These patients will be then transitioned to maintenance therapy.

Maintenance therapy:

Maintenance therapy will consist of:

* Dexamethasone 20mg weekly days 1, 8, 15, 22 out of a 28 day cycle)
* Lenalidomide 25 mg/daily days 1 - 21 out of a 28 day cycle. 15mg/daily on days 1-21 of a 28 day cycle of lenalidomide will be given to patients with a creatinine clearance of \< 40cc/min\*

  * Patients who finished induction therapy with DexTR at a reduced dose of lenalidomide will start maintenance therapy at the same dose of lenalidomide on which they ended induction therapy. For patients with a creatinine clearance of \< 40cc / minute, the lenalidomide dose will be the lower of their last induction therapy dose or 15mg daily on days 1 - 21 out of a 28 day cycle.

Serial clinic visits and laboratory measurements will be performed to monitor for treatment response. Those patients who demonstrate progression of disease at any point during DexTR therapy will be taken off study.

At the end of every cycle (which may coincide with day 1 of the new cycle), response and toxicity will be evaluated. During cycle 1, patients will have lab work done weekly (CBC with differential and blood electrolytes). All patients will remain on study until disease progression or side effects become excessive. Patients who achieve a stable plateau and are on maintenance therapy as defined above may be taken off study if eligible to proceed to high dose chemotherapy and autologous stem cell transplantation.

Arms: arm 1: All patients were treated with the DexTR (dexamethasone / thalidomide, lenalidomide (Revlimid®)), which consisted of lenalidomide 25mg/day during days 1-21, dexamethasone 40mg/day on days 1-4, 9-12, and 17-20, and thalidomide 50mg/day for the first 7 days, followed by 100mg/day for all subsequent days, for a total of 4 cycles of 28 days each.
Interventions: intervention 1: dexamethasone intervention 2: thalidomide intervention 3: lenalidomide
Intervention descriptions: intervention 1: Cycles 1-4 • Dexamethasone (40mg ) will be given on days 1-4, 9-12, 17-20 of a 28-day cycle.

After completing 4 cycles:

* Patients who demonstrate disease progression at any time will be taken off study.
* Patients who achieve a resolution of monoclonal gammopathy as detected on serum immunofixation or achieve a plateau of disease (no change in M-spike as detected on serum protein electrophoresis) for \> 2 cycles will be transitioned to maintenance therapy.
* Patients who continue to respond without achieving either a plateau or a CR will continue on induction therapy until plateau for \>2 cycles or CR in the absence of untoward toxicity. These patients will be then transitioned to maintenance therapy.

Maintenance therapy will consist of:

• Dexamethasone 20mg weekly days 1, 8, 15, 22 out of a 28 day cycle) intervention 2: Cycles 1-4

• Thalidomide will be given 50mg daily on days 1-7, thereafter 100mg daily on days 8-28 of the first 28-day cycle. Thalidomide will then be given at 100mg/daily for days 1-28 of each subsequent cycle.

After completing 4 cycles:

* Patients who demonstrate disease progression at any time will be taken off study.
* Patients who achieve a resolution of monoclonal gammopathy as detected on serum immunofixation or achieve a plateau of disease (no change in M-spike as detected on serum protein electrophoresis) for \> 2 cycles will be transitioned to maintenance therapy.
* Patients who continue to respond without achieving either a plateau or a CR will continue on induction therapy until plateau for \>2 cycles or CR in the absence of untoward toxicity. These patients will be then transitioned to maintenance therapy. intervention 3: Cycles 1-4 • Lenalidomide will be given 25mg daily for days 1-21 of each 28 day cycle.

After completing 4 cycles:

* Patients who demonstrate disease progression at any time will be taken off study.
* Patients who achieve a resolution of monoclonal gammopathy as detected on serum immunofixation or achieve a plateau of disease (no change in M-spike as detected on serum protein electrophoresis) for \> 2 cycles will be transitioned to maintenance therapy.
* Patients who continue to respond without achieving either a plateau or a CR will continue on induction therapy until plateau for \>2 cycles or CR in the absence of untoward toxicity. These patients will be then transitioned to maintenance therapy.

Maintenance therapy will consist of:

• Lenalidomide 25 mg/daily days 1 - 21 out of a 28 day cycle. 15mg/daily on days 1-21 of a 28 day cycle of lenalidomide will be given to patients with a creatinine clearance of \< 40cc/min\*

Protocol documents: