Conditions: Multiple Myeloma
Keywords: myeloma newly diagnosed multiple myeloma
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 26
Healthy volunteers: no

Brief summary:
Study Objectives

1. Evaluate the efficacy of the combination of thalidomide (Thalomid®), clarithromycin (Biaxin®), lenalidomide (Revlimid®), and dexamethasone (Decadron®) as an induction therapy for patients with newly diagnosed multiple myeloma (MM).
2. Evaluate the efficacy of the addition of thalidomide (Thalomid®) to BiRD combination therapy as a therapy to increase the complete response rate for patients with newly diagnosed multiple myeloma.
3. Evaluate the safety of the combination of clarithromycin, lenalidomide, dexamethasone, and thalidomide as a therapy for patients with newly diagnosed MM

Detailed description:
This phase II study is a treatment program for patients with newly diagnosed multiple myeloma. Up to 25 patients will be enrolled. Patients who sign consent and fulfill all eligibility criteria will be enrolled to receive the following treatment plan:

T-BiRD Therapy:

Cycles 1-4

* Thalidomide (50mg daily for days 1-7, thereafter 100mg daily for days 8-28 of the first 28 day cycle. Thalidomide will then be given at 100mg/daily for days 1-28 for each subsequent cycle)
* Clarithromycin (500mg twice daily for each 28 day cycle)
* Lenalidomide (25 mg daily days 1-21 of every 28 day cycle) and
* Dexamethasone (40 mg daily on day 1, 8, 15 and 22 of each 28 day cycle)
* Prophylactic medications will be given.

After completing 4 cycles

* Patients who demonstrate progression of disease will be taken off study.
* Patients who achieve maximum response (either by achievement of complete remission or stable disease plateau) will be transitioned to maintenance therapy.
* Patients who achieve VGPR or PR with acceptable toxicity will be given T-BiRD for an additional 2 cycles: cycles 5 and 6.

Upon completion of 6 cycles of T-BiRD,

* Patients who achieve maximum response (either by achievement of complete remission or stable disease plateau) will be transitioned to maintenance therapy.
* Patients without disease progression or maximum response (either by achievement of complete remission or stable disease plateau) will receive BiRD therapy
* Patients with disease progression will be taken off study.

BiRD therapy will consist of the following:

* Clarithromycin (500mg twice daily for each 28 day cycle)\*
* Lenalidomide (25mg daily days 1-21 of every 28 day cycle)\*
* Dexamethasone (40mg on days 1, 8, 15, 22 of each 28 day cycle)\*
* Prophylactic medications will be continued.

  * Patients who finished T-BiRD therapy at reduced doses of clarithromycin, lenalidomide or dexamethasone will start BiRD therapy at the same doses of clarithromycin, lenalidomide and dexamethasone on which they ended T-BiRD therapy.

Patients who progress on BiRD will reinitiate T-BiRD as follows:

* Thalidomide (100mg/daily for days 1-28 for each 28 day cycle)
* Clarithromycin (500mg twice daily for each 28 day cycle)\*
* Lenalidomide (25mg/daily for days 1-21 of each 28 day cycle)\*
* Dexamethasone (40mg days 1, 8, 15, 22 of each 28 day cycle)\*
* Prophylactic medications will be continued
* Patients who continue to show disease progression after two cycles of T-BiRD will be taken off study.

  * Patients who finished BiRD therapy at reduced doses of clarithromycin, lenalidomide or dexamethasone will start T-BiRD therapy at the same doses of clarithromycin, lenalidomide and dexamethasone on which they ended BiRD therapy.

Transition to maintenance therapy:

Patients who achieve a resolution of monoclonal gammopathy as detected on serum immunofixation or achieve a plateau of disease (no change in quantitative M-spike as detected on serum immunofixation) for \> 2 cycles on either BiRD or T-BiRD therapy will be transitioned to maintenance therapy. Maintenance therapy will be comprised of:

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

  * Patients who finished induction therapy with BiRD or T-BiRD at reduced doses lenalidomide or dexamethasone will start maintenance therapy at the same doses lenalidomide and dexamethasone 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.

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) and female of childbearing potential will have their pregnancy testing done, see APPENDIX III. 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 same regimen, starting with T-BIRD therapy (Cycles 1-4).

After 4 cycles, Patients with disease progression will be taken off study. Patients who achieve maximum response will receive maintenance. Patients who achieve VGPR or PR will be given T-BiRD for 2 cycles (cycles 5-6). After 6 cycles of T-BiRD, Patients who achieve maximum response will receive maintenance; those with disease progression will be taken off study; all other patients will receive BIRD.

Patients who progress on BiRD will reinitiate T-BiRD. If disease progression continues after 2 cycles, patients will be taken off study.

Patients in CR/sCR or that achieve a plateau of disease for \> 2 cycles on BiRD or T-BiRD therapy will receive maintenance.

Interventions: intervention 1: thalomid intervention 2: lenalidomide intervention 3: clarithromycin intervention 4: dexamethasone
Intervention descriptions: intervention 1: Cycles 1-4

• Thalidomide (50mg daily for days 1-7, thereafter 100mg daily for days 8-28 of the first 28 day cycle. Thalidomide will then be given at 100mg/daily for days 1-28 for each subsequent cycle) intervention 2: During T-BIRD Phase (Cycles 1-4, 5-6, and in the case of T-BIRD re-initiation)

• Lenalidomide (25 mg daily days 1-21 of every 28 day cycle)

During BiRD phase • 25mg daily days 1-21 of every 28 day cycle)

During Maintenance Phase

• 25 mg daily for days 1-21 out of a 28 day cycle intervention 3: During T-BiRD Phase • Clarithromycin (500mg twice daily for each 28 day cycle)

During BiRD Phase:

• Clarithromycin (500mg twice daily for each 28 day cycle) intervention 4: During T-BIRD Phase (Cycles 1-4, 5-6, and in the case of T-BIRD re-initiation)

• Dexamethasone (40 mg daily on day 1, 8, 15 and 22 of each 28 day cycle)

During BiRD Phase:

• Dexamethasone (40 mg daily on day 1, 8, 15 and 22 of each 28 day cycle)

During Maintenance Phase

• Dexamethasone 20 mg weekly (days 1,8, 15, 22 out of a 28 day cycle)

Protocol document: