This trial is active, not recruiting.

Condition multiple myeloma
Treatments azacitidine, lenalidomide
Sponsor Virginia Commonwealth University
Collaborator National Cancer Institute (NCI)
Start date January 2010
End date August 2014
Trial size 17 participants
Trial identifier NCT01050790, CDR0000663409, MCC-12430, P30CA016059


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.

United States No locations recruiting
Other countries No locations recruiting

Study Design

Intervention model single group assignment
Masking open label
Primary purpose treatment
azacitidine Vidaza®
75 mg/sq m daily for 5 days
lenalidomide CC-5013
10 mg p.o. daily, Days 6-21

Primary Outcomes

Feasibility to mobilize and infuse autologous lymphocytes (ALI) after immunomodulatory therapy
time frame: 2 years

Secondary Outcomes

Complete response rate at 6 months
time frame: 2 years
Toxicity as assessed by NCI CTCAE v3.0
time frame: 2 years
Time to progression
time frame: 2 years
Progression-free and overall survival
time frame: 2 years
Pre- and post-ALI immune response to cancer testis antigens (CTA)
time frame: 2 years
CTA expression before and after azacitidine therapy
time frame: 2 years

Eligibility Criteria

Male or female participants from 18 years up to 70 years old.

INCLUSION CRITERIA: - Patients with a diagnosis of multiple myeloma - Eligible to undergo an autologous stem cell transplant - Has residual measurable disease (in partial remission [PR] or with stable disease) - Measurable disease: - quantifiable serum - urinary M protein - free light chains in the presence of a positive immunofixation - bone marrow plasma cells >5% NOTE: Isolated bone lytic lesions in the absence of measurable para-proteins will not be considered measurable disease - received prior lenalidomide therapy will be eligible (if >PR was observed or did not progress on lenalidomide containing regimen) - Progression following discontinuation of prior therapy with lenalidomide is allowed as long as patients have not failed rechallenge with lenalidomide - A minimum period of two weeks must have elapsed following the prior myeloma therapy (this does not include therapy with bisphosphonates) - Patients ages ≤ 18 and <70 years of age - ECOG performance status ≤ 2 - Negative serology for HIV - Serum bilirubin ≤ 1.5 times - SGOT/SGPT <3xULN - Creatinine clearance >60 ml/min or or serum creatinine ≤ 2.0 mg/dL - ANC≥1500/L - platelet count ≥100,000/L - Hemoglobin ≥10 g/dL - No clinical evidence of uncontrolled viral, fungal, bacterial infection - Cardiac and pulmonary function adequate for transplant - Ability to sign informed consent - Registered into mandatory RevAssist program and comply with requirements - Females of childbearing potential (FCBP)† must have: - Negative serum or urine pregnancy test within 10 - 14 days prior to, within 24 hours of prescribing lenalidomide - Either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control at least 28 days before treatment. - Agree to ongoing pregnancy testing - Men must agree to use a latex condom during sexual contact with FCBP EXCLUSION CRITERIA - Known or suspected hypersensitivity to azacitidine or mannitol - Patients with MM refractory to therapy with lenalidomide - Pregnant or breast feeding - Other concomitant malignancies - Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form - Concurrent use of other anti-cancer agents or treatments - Known hypersensitivity to thalidomide or lenalidomide

Additional Information

Official title Lenalidomide and Azacitidine for Adaptive Immunotherapy in Multiple Myeloma: Pilot Study of Autologous Lymphocyte Mobilization Following Immuno-modulatory Therapy
Principal investigator Amir A. Toor, MD
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.
Trial information was received from ClinicalTrials.gov and was last updated in April 2015.
Information provided to ClinicalTrials.gov by Virginia Commonwealth University.