Clinical trial NCT01050790
Conditions: Multiple Myeloma
Keywords: stage I multiple myeloma stage II multiple myeloma stage III multiple myeloma
Sponsor: Virginia Commonwealth University
Start date: 2010-01-01; Completion date: 2016-09-01
Enrollment: 17 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
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 pilot 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.

Detailed description:
OBJECTIVES:

Primary

* Determine the feasibility of mobilizing and infusing autologous lymphocytes (ALI) following immunomodulatory therapy comprising azacitidine and lenalidomide in patients with multiple myeloma.

Secondary

* 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.

OUTLINE:

* 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.

Arms: arm 1: Azacitidine will be administered to all the patients subcutaneously at a dose of 75 mg/m2 daily for five days(day 1-5). These cycles will be repeated at 28 day intervals depending on hematopoietic recovery. Starting on day 6 patients will receive lenalidomide 15 mg PO daily until day 21. No drug will be administered from day 22 to day 28. Lymphapheresis will occur after cycles 2 and 3.Patients will undergo a stem cell collection approximately two weeks after complete myeloid recovery from the third cycle of therapy. Stem Cell Transplant (SCT) will occur per transplant center protocols. Post-transplant single or tandem autologous lymphocyte infusions (ALI) will be performed no earlier than 30 days post-transplant and no later than 40 days.
Interventions: intervention 1: Azacitidine
Intervention descriptions: intervention 1: Subject will receive Vidaza (azacitidine) and Revlimid (lenalidomide) as treatment for their multiple myeloma. The Vidaza will be given for 5 days as an injection. On day 6 they will receive Revlimid taken by mouth every day for 16 days followed by 7 days of rest. The drug cycle will be repeated 0, 1 or 2 more times depending on how their blood counts recover.

Protocol documents: