Lenalidomide + Azacitidine for Adaptive Immunotherapy -> Auto SCT in Multiple Myeloma

This study is ongoing, but not recruiting participants.
National Cancer Institute (NCI)
Celgene Corporation
Information provided by (Responsible Party):
Virginia Commonwealth University
ClinicalTrials.gov Identifier:
First received: January 14, 2010
Last updated: March 31, 2016
Last verified: March 2016

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.

Condition Intervention
Multiple Myeloma
Drug: Azacitidine

Study Type: Interventional
Study Design: 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

Resource links provided by NLM:

Further study details as provided by Virginia Commonwealth University:

Primary Outcome Measures:
  • Feasibility to Mobilize and Infuse Autologous Lymphocytes (ALI) After Immunomodulatory Therapy and After Stem Cell Transplant Engraftment [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Time frame is post 2nd and 3rd cycles of rev/aza and after stem cell transplant engraftment.

Secondary Outcome Measures:
  • Complete Response Rate at 6 Months [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    16 of 17 patients proceeded to transplant. 6 month CR rate post transplant was 8/16 (50%).

  • Toxicity as Assessed by NCI CTCAE v3.0 [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    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.

  • Time to Progression Post Transplant [ Time Frame: 28 months ] [ Designated as safety issue: No ]
    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.

  • Progression-free and Overall Survival [ Time Frame: 1 year to 2 years ] [ Designated as safety issue: No ]

    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%).

  • Pre- and Post-ALI Immune Response to Cancer Testis Antigens (CTA) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Not able to obtain outcome data.

  • CTA Expression Before and After Azacitidine Therapy [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    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.

Enrollment: 17
Study Start Date: January 2010
Estimated Study Completion Date: August 2017
Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Aza Len Lymphapheresis SCT ALI
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.
Drug: Azacitidine
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.
Other Names:
  • Vidaza®
  • lenalidomide
  • CC-5013
  • Revlimid

Detailed Description:



  • 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.


Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

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
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01050790

United States, Virginia
Virginia Commonwealth University
Richmond, Virginia, United States, 23298
Sponsors and Collaborators
Virginia Commonwealth University
National Cancer Institute (NCI)
Celgene Corporation
Principal Investigator: Amir A. Toor, MD Massey Cancer Center
  More Information

Responsible Party: Virginia Commonwealth University
ClinicalTrials.gov Identifier: NCT01050790     History of Changes
Other Study ID Numbers: CDR0000663409  P30CA016059  MCC-12430 
Study First Received: January 14, 2010
Results First Received: July 16, 2015
Last Updated: March 31, 2016
Health Authority: United States: Institutional Review Board

Keywords provided by Virginia Commonwealth University:
stage I multiple myeloma
stage II multiple myeloma
stage III multiple myeloma

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Blood Protein Disorders
Cardiovascular Diseases
Hematologic Diseases
Hemorrhagic Disorders
Hemostatic Disorders
Immune System Diseases
Immunoproliferative Disorders
Lymphoproliferative Disorders
Neoplasms by Histologic Type
Vascular Diseases
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Antimetabolites, Antineoplastic
Antineoplastic Agents
Enzyme Inhibitors
Growth Inhibitors
Growth Substances
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on May 26, 2016