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

This study is ongoing, but not recruiting participants.
Celgene Corporation
Information provided by (Responsible Party):
Virginia Commonwealth University Identifier:
First received: January 14, 2010
Last updated: December 19, 2014
Last verified: December 2014

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.

Condition Intervention
Multiple Myeloma
Drug: azacitidine
Drug: lenalidomide

Study Type: Interventional
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

Resource links provided by NLM:

Further study details as provided by Virginia Commonwealth University:

Primary Outcome Measures:
  • Ability to mobilize and infuse autologous lymphocytes (ALI) after immunomodulatory therapy [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 19
Study Start Date: January 2010
Estimated Study Completion Date: January 2017
Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 5-azacytidine + lenalidomide -> auto stem cell transplant Drug: azacitidine
75 mg/sq m daily for 5 days
Other Name: Vidaza®
Drug: lenalidomide
10 mg p.o. daily, Days 6-21
Other Names:
  • 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 69 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No


  • Diagnosis of multiple myeloma (MM)

    • Has residual measurable disease* (in partial remission [PR] or with stable disease), as defined by either of the following:

      • Quantifiable levels of serum or urinary M protein or free-light chains in the presence of a positive immunofixation
      • Bone marrow plasma cells > 5% NOTE: *Isolated lytic bone lesions in the absence of measurable para-proteins not considered measurable disease
  • Not refractory to lenalidomide

    • At least a PR was observed on a prior lenalidomide-containing regimen AND patient did not progress while receiving lenalidomide
    • Patients who progress after discontinuation of lenalidomide treatment are eligible provided they have not failed rechallenge with lenalidomide
  • Eligible to undergo autologous stem cell transplantation (ASCT)

    • Meets the requirements for ASCT per Virginia Commonwealth University BMT SOP 6.00


  • ECOG performance status 0-2
  • ANC ≥ 2,000/μL
  • Platelet count ≥ 100,000/μL
  • Hemoglobin ≥ 10 g/dL
  • Serum bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • SGOT and/or SGPT ≤ 3 times ULN
  • Creatinine clearance ≥ 60 mL/min OR serum creatinine ≤ 2.0 mg/dL
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use two effective methods of contraception for ≥ 4 weeks before, during, and for ≥ 4 weeks after completion of study therapy
  • Registered in the RevAssist® program AND willing and able to comply with the requirements of RevAssist®
  • Adequate cardiac and pulmonary function for transplant
  • No known HIV positivity
  • No clinical evidence of uncontrolled viral, fungal, or bacterial infection
  • No known or suspected hypersensitivity to azacitidine, mannitol, thalidomide, or lenalidomide
  • No other concurrent malignancies
  • No other serious medical condition, laboratory abnormality, or psychiatric illness that would preclude giving informed consent


  • See Disease Characteristics
  • At least 2 weeks since prior myeloma therapy (other than bisphosphonates)

    • Concurrent bisphosphonates allowed
  • No other concurrent anticancer agents or treatments
  Contacts and Locations
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Please refer to this study by its identifier: NCT01050790

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

Additional Information:
No publications provided

Responsible Party: Virginia Commonwealth University Identifier: NCT01050790     History of Changes
Other Study ID Numbers: CDR0000663409, P30CA016059, MCC-12430
Study First Received: January 14, 2010
Last Updated: December 19, 2014
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
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses processed this record on March 03, 2015