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

NCT01050790 | Completed Results DMC

• 3 other identifiers: CDR0000663409P30CA016059MCC-12430
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Multiple Myeloma

Keywords

stage I multiple myeloma; stage II multiple myeloma; stage III multiple myeloma

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• Complete Response Rate at 6 Months

  6 months

• Toxicity as Assessed by NCI CTCAE v3.0

  6 months

• Time to Progression Post Transplant

  28 months

• Progression-free and Overall Survival

  1 year to 2 years

• Pre- and Post-ALI Immune Response to Cancer Testis Antigens (CTA)

  6 months

Study Arms (1)

Aza Len Lymphapheresis SCT ALI

EXPERIMENTAL

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

Interventions

Azacitidine DRUG

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.

Also known as: Vidaza®, lenalidomide, CC-5013, Revlimid

Aza Len Lymphapheresis SCT ALI

Eligibility Criteria

• Age: 18 Years - 69 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Virginia Commonwealth University: lead
• National Cancer Institute (NCI): collaborator
• Celgene Corporation: collaborator

Study Sites (1)

Virginia Commonwealth University

Richmond, Virginia, 23298, United States

Location

Related Publications (1)

• 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 cancer testis antigen-specific cellular immunity. Br J Haematol. 2012 Sep;158(6):700-11. doi: 10.1111/j.1365-2141.2012.09225.x. Epub 2012 Jul 23.

  PMID: 22816680 RESULT

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Azacitidine; Lenalidomide

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Piperidones; Piperidines; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Amir A. Toor, MD, Associate Professor of Medicine
• Organization: Virginia Commonwealth University/Massey Cancer Center

atoor@mcvh-vcu.edu

804-828-4360

Study Officials

• Amir A. Toor, MD

  Massey Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 14, 2010
• First Posted: January 15, 2010
• Study Start: January 1, 2010
• Primary Completion: August 1, 2014
• Study Completion: September 1, 2016
• Last Updated: June 26, 2018
• Results First Posted: October 5, 2015

Record last verified: 2016-10

Locations

US (1)