Multiple Myeloma Clinical Trial
Official title:
Lenalidomide and Azacitidine for Adaptive Immunotherapy in Multiple Myeloma: Pilot Study of Autologous Lymphocyte Mobilization Following Immuno-modulatory Therapy
Verified date | October 2016 |
Source | Virginia Commonwealth University |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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.
Status | Completed |
Enrollment | 17 |
Est. completion date | September 2016 |
Est. primary completion date | August 2014 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years to 69 Years |
Eligibility |
Inclusion criteria: - Patients with a diagnosis of multiple myeloma, who have residual measurable disease (in partial remission or with stable disease) and are eligible to undergo an autologous stem cell transplant will be able to participate in this trial; measurable disease will comprise of either, quantifiable serum or urinary, M protein or free light chains in the presence of a positive immunofixation or bone marrow plasma cells > 5% - Patients who have received prior lenalidomide therapy will be eligible if >= partial response (PR) was observed on a prior lenalidomide containing regimen and patients did not progress while receiving lenalidomide; isolated bone lytic lesions in the absence of measurable para-proteins will not be considered measurable disease - A minimum period of two weeks must have elapsed following the prior myeloma therapy; this does not include therapy with bisphosphonates - Eastern Cooperative Oncology Group (ECOG) performance status =< 2 - No clinical evidence of uncontrolled viral, fungal, bacterial infection - Negative serology for human immunodeficiency virus (HIV) - Serum bilirubin =< 1.5 times upper limit of normal (ULN) - Serum glutamic oxaloacetic transaminase (SGOT)/serum glutamic pyruvic transaminase (SGPT) =< 3x ULN - Calculated creatinine clearance >= 60ml/min by Cockcroft-Gault formula; creatinine clearance >= 60 ml/min or serum creatinine =< 2.0 mg/dL - Absolute neutrophil count (ANC) >= 1500/uL - Platelet count >= 100,000/ uL - Hemoglobin (Hgb) >= 10 g/dL following recovery from last therapy - Cardiac and pulmonary function adequate for transplant - Ability to sign informed consent - All study participants must be registered into the mandatory RevAssist program, and be willing and able to comply with the requirements of RevAssist - Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 10-14 days prior to and again within 24 hours of prescribing lenalidomide (prescriptions must be filled within 7 days) and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking lenalidomide; FCBP must also agree to ongoing pregnancy testing - Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy Exclusion criteria: - Known or suspected hypersensitivity to azacitidine or mannitol - Patients with multiple myeloma refractory to therapy with lenalidomide; progression following discontinuation of prior therapy with lenalidomide is allowed as long as patients have not failed rechallenge 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 |
Country | Name | City | State |
---|---|---|---|
United States | Virginia Commonwealth University | Richmond | Virginia |
Lead Sponsor | Collaborator |
---|---|
Virginia Commonwealth University | Celgene Corporation, National Cancer Institute (NCI) |
United States,
Toor AA, Payne KK, Chung HM, Sabo RT, Hazlett AF, Kmieciak M, Sanford K, Williams DC, Clark WB, Roberts CH, McCarty JM, Manjili MH. Epigenetic induction of adaptive immune response in multiple myeloma: sequential azacitidine and lenalidomide generate canc — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Feasibility to Mobilize and Infuse Autologous Lymphocytes (ALI) After Immunomodulatory Therapy and After Stem Cell Transplant Engraftment | Time frame is post 2nd and 3rd cycles of rev/aza and after stem cell transplant engraftment. | 6 months | |
Secondary | Complete Response Rate at 6 Months | 16 of 17 patients proceeded to transplant. 6 month CR rate post transplant was 8/16 (50%). | 6 months | |
Secondary | Toxicity as Assessed by NCI CTCAE v3.0 | Time frame includes after stem cell transplant engraftment. Toxicity post ALI infusion: 1 patient grade 1 hypertension 90 min post infusion. Toxicity post Rev maintenance: 1 patient not tolerated, 1 patient dose decreased due to counts. | 6 months | |
Secondary | Time to Progression Post Transplant | Time to progression post transplant: For patients not in Complete Response (CR), progressive disease requires one or more: >25% increase in the level of the serum monoclonal paraprotein(absolute increase of at least 0.5 g/dL); > 25% increase in 24-hour urinary light chain excretion(absolute increase of at least 200m/24 hours). Increase plasma cells in a bone marrow aspirate( absolute increase of at least 10%). Definite increase in the size of existing bone lesions or soft tissue plasmacytomas. Development of new bone lesions or soft tissue plasmacytomas. Development of hypercalcemia (corrected serum Ca > 11.5 mg/dL or > 2.65 mmol/L) not attributable to any other cause. All relapse categories require two consecutive assessments made any time before classification as relapse or progressive disease. | 28 months | |
Secondary | Progression-free and Overall Survival | Survival and event-free survival curves (any event of fatality, relapse, acute or chronic GVHD) with Kaplan-Meier curves. The incidence curve for relapse - accounting for the competing risk of fatality - is plotted with step-wise curves. The R statistical software (version 2.15) was used for all time-to-event analyses, with the survival package used for survival curves, and the cmprsk package used for all competing risk curves. Results: The one-year survival rate is 93.3% (SE = 0.4%), and the two-year survival rate is 86.1% (SE = 0.9%). |
1 year to 2 years | |
Secondary | Pre- and Post-ALI Immune Response to Cancer Testis Antigens (CTA) | Not able to obtain outcome data. | 6 months | |
Secondary | CTA Expression Before and After Azacitidine Therapy | Six patients tested have demonstrated CTA up-regulation in either unfractionated bone marrow (n = 4) or CD138+ cells (n = 2). CTA (CTAG1B)-specific T cell response has been observed in all three patients tested and persists following SCT. | 3 months |
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