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
ClinicalTrials.gov Identifier:
First received: January 14, 2010
Last updated: March 24, 2015
Last verified: March 2015

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


  • 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


  • 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
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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
Celgene Corporation
Principal Investigator: Amir A. Toor, MD Massey Cancer Center
  More Information

Additional Information:
No publications provided

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
Last Updated: March 24, 2015
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

ClinicalTrials.gov processed this record on March 30, 2015