Lenalidomide + Azacitidine for Adaptive Immunotherapy -> Auto SCT in Multiple Myeloma
RATIONALE: Lenalidomide may stimulate the immune system in different ways and stop cancer cells from growing. Drugs used in chemotherapy, such as azacitidine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. An autologous stem cell transplant may be able to replace blood-forming cells that were destroyed by lenalidomide and azacitidine. Giving autologous lymphocytes after the transplant may help destroy any remaining cancer cells.
PURPOSE: This phase I trial is studying how well giving lenalidomide together with azacitidine works when followed by autologous stem cell transplant and autologous lymphocyte infusion in treating patients with multiple myeloma.
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Lenalidomide and Azacitidine for Adaptive Immunotherapy in Multiple Myeloma: Pilot Study of Autologous Lymphocyte Mobilization Following Immuno-modulatory Therapy|
- Ability to mobilize and infuse autologous lymphocytes (ALI) after immunomodulatory therapy [ Time Frame: 2 years ] [ Designated as safety issue: No ]
- Complete response rate at 6 months [ Time Frame: 2 years ] [ Designated as safety issue: No ]
- Toxicity as assessed by NCI CTCAE v3.0 [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
- Time to progression [ Time Frame: 2 years ] [ Designated as safety issue: No ]
- Progression-free and overall survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
- Pre- and post-ALI immune response to cancer testis antigens (CTA) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
- CTA expression before and after azacitidine therapy [ Time Frame: 2 years ] [ Designated as safety issue: No ]
|Study Start Date:||January 2010|
|Estimated Study Completion Date:||January 2017|
|Primary Completion Date:||August 2014 (Final data collection date for primary outcome measure)|
|Experimental: 5-azacytidine + lenalidomide -> auto stem cell transplant||
75 mg/sq m daily for 5 days
Other Name: Vidaza®Drug: lenalidomide
10 mg p.o. daily, Days 6-21
- Determine the feasibility of mobilizing and infusing autologous lymphocytes (ALI) following immunomodulatory therapy comprising azacitidine and lenalidomide in patients with multiple myeloma.
- Determine the ability to proceed with autologous stem cell transplantation in these patients.
- Determine the complete response rate at 6 months following transplant in patients treated with this regimen.
- Determine the progression-free survival and overall survival of patients treated with this regimen.
- Determine the time to progression in patients treated with this regimen.
- Monitor the toxicity of post-autologous stem cell infusion of autologous lymphocytes.
- Measure the pre- and post-ALI immune response to cancer testis antigens (CTA) (CTA-specific Ig and T-cell repertoire).
- Study the expression of CTA in multiple myeloma before and after azacitidine therapy.
- Immunomodulatory therapy: Patients receive azacitidine subcutaneously on days 1-5 and oral lenalidomide on days 6-21. Treatment repeats every 28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.
- Lymphapheresis: Patients undergo autologous lymphocyte harvest on day 22 of courses 2 and 3.
- Autologous stem cell transplantation (ASCT): Patients undergo single or tandem ASCT using standard protocols.
- Autologous lymphocyte infusion (ALI): Patients undergo ALI approximately 28-60 days after ASCT.
Blood samples are collected at baseline and periodically during study for correlative laboratory studies, including CTA-specific immune monitoring by RT-PCR, ELISPOT assays, and flow cytometry. Tissue samples from bone marrow aspirates are also collected at baseline, during course one, and after course three for CTA expression and methylation studies.
After completion of study therapy, patients are followed periodically.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01050790
|United States, Virginia|
|Virginia Commonwealth University|
|Richmond, Virginia, United States, 23298|
|Principal Investigator:||Amir A. Toor, MD||Massey Cancer Center|