Multiple MyelomaNCT01050790
Lenalidomide + Azacitidine for Adaptive Immunotherapy -> Auto SCT in Multiple Myeloma
A study testing Azacitidine in people with Multiple Myeloma, run by Virginia Commonwealth University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 69 years
- Conditions the study is for
- Multiple Myeloma
- What is being tested?
- Azacitidine
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2010to Sep 2016
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 69 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Show all 17Show fewer
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Virginia Commonwealth University
Richmond, Virginia, 23298
About this study
Official title: Lenalidomide and Azacitidine for Adaptive Immunotherapy in Multiple Myeloma: Pilot Study of Autologous Lymphocyte Mobilization Following Immuno-modulatory Therapy
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.
Read the detailed description
OBJECTIVES:
Primary
- Determine the feasibility of mobilizing and infusing autologous lymphocytes (ALI) following immunomodulatory therapy comprising azacitidine and lenalidomide in patients with multiple myeloma.
Secondary
- 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.
OUTLINE:
- 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.
- Conditions
- Multiple Myeloma
- Being tested
- Azacitidine
- Keywords
- stage I multiple myeloma, stage II multiple myeloma, stage III multiple myeloma
- Medical subject headings
- Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AzacitidineDrug
Also called Vidaza®, lenalidomide, CC-5013, Revlimid
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Azacitidine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 6 months
Secondary outcomes (6)
Complete Response Rate at 6 Months
16 of 17 patients proceeded to transplant. 6 month CR rate post transplant was 8/16 (50%).
Measured: 6 months
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.
Measured: 6 months
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.
Measured: 28 months
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%).
Measured: 1 year to 2 years
Pre- and Post-ALI Immune Response to Cancer Testis Antigens (CTA)
Not able to obtain outcome data.
Measured: 6 months
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.
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jan 2010 (estimated)
- Study startJan 2010
- Primary completionAug 2014
- Study completionSep 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Multiple MyelomaStudies of the same condition, open and under way.
- More trials run by Virginia Commonwealth UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- Virginia Commonwealth University
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI), Celgene Corporation
- Responsible party
- Sponsor
- Investigators
- Amir A. Toor, MD, Principal investigator, Massey Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01050790
- Sponsor's protocol ID
- CDR0000663409
- Other IDs
- P30CA016059, MCC-12430
- Status last verified
- Oct 2016
- First submitted
- 14 Jan 2010
- Last updated
- 26 Jun 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 22816680
Study at a glance
From the registry record, last updated by the sponsor on 26 Jun 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Lenalidomide and Azacitidine for Adaptive Immunotherapy in Multiple Myeloma: Pilot Study of Autologous Lymphocyte Mobilization Following Immuno-modulatory Therapy
- ClinicalTrials.gov ID
- NCT01050790
- Acronym / sponsor ID
- CDR0000663409
- Conditions
- Multiple Myeloma
- Keywords
- stage I multiple myeloma, stage II multiple myeloma, stage III multiple myeloma
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 17 participants (actual)
- Lead sponsor
- Virginia Commonwealth UniversityUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI), Celgene Corporation
- Study start
- Jan 2010
- Primary completion
- Aug 2014 (actual)
- Study completion
- Sep 2016 (actual)
- First posted
- 15 Jan 2010 (estimated)
- Results
- Posted 5 Oct 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
OBJECTIVES:
Primary
- Determine the feasibility of mobilizing and infusing autologous lymphocytes (ALI) following immunomodulatory therapy comprising azacitidine and lenalidomide in patients with multiple myeloma.
Secondary
- 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.
OUTLINE:
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Aza Len Lymphapheresis SCT ALI | Experimental | Drug: AzacitidineAzacitidine 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. |
Who may qualify
- Ages
- 18 to 69 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- 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
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AzacitidineAlso: Vidaza®, lenalidomide, CC-5013, RevlimidSubject 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. | Drug | Aza Len Lymphapheresis SCT ALI |
Primary outcome
Feasibility to Mobilize and Infuse Autologous Lymphocytes (ALI) After Immunomodulatory Therapy and After Stem Cell Transplant Engraftment
Time frame: 6 months
Time frame is post 2nd and 3rd cycles of rev/aza and after stem cell transplant engraftment.
6 secondary outcomes
Complete Response Rate at 6 Months
Time frame: 6 months
Toxicity as Assessed by NCI CTCAE v3.0
Time frame: 6 months
Time to Progression Post Transplant
Time frame: 28 months
Progression-free and Overall Survival
Time frame: 1 year to 2 years
Pre- and Post-ALI Immune Response to Cancer Testis Antigens (CTA)
Time frame: 6 months
CTA Expression Before and After Azacitidine Therapy
Time frame: 3 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jun 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 22816680Toor 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Amir A. Toor, MD principal investigator
Massey Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Azacitidine in people with Multiple Myeloma, run by Virginia Commonwealth University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Jun 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Oct 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Feasibility to Mobilize and Infuse Autologous Lymphocytes (ALI) After Immunomodulatory Therapy and After Stem Cell Transplant Engraftment (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01050790, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Jun 2018.