Multiple MyelomaPhase 2aMILsNCT01045460
Trial of Activated Marrow Infiltrating Lymphocytes Alone or in Conjunction With an Allogeneic Granulocyte Macrophage Colony-stimulating Factor (GM-CSF)-Based Myeloma Cellular Vaccine in the Autologous Transplant Setting in Multiple Myeloma
A Phase 2 study testing Activated marrow infiltrating lymphocytes, Allogeneic Myeloma Vaccine and Cyclophosphamide in people with Multiple Myeloma, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 1 site in United States.
Trial summary
Patient Population: Patients with active myeloma (Stage II/III) that have completed induction therapy and are eligible for an autologous stem cell transplant. Number of Patients: Will treat a total of 32 evaluable patients in a 1:1 randomization of aMILs vs aMILs plus vaccine. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Multiple Myeloma
- What is being tested?
- Activated marrow infiltrating lymphocytes, Allogeneic Myeloma Vaccine and Cyclophosphamide
- Type of treatment
- Vaccines, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Jan 2010to Jun 2020
- Phase
- Phase 2
- 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 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Durie-Salmon Stage II or III multiple myeloma
- Newly diagnosed either prior to receiving treatment or having completed induction therapy
- Relapsed myeloma not previously transplanted within the past 5 years
- Measurable serum and/or urine M-protein from prior to induction therapy documented and available. A positive serum free lite assay is acceptable
- Age greater than 18 years old
- ECOG performance status of 0 - 2
- Meet all institutional requirements for autologous stem cell transplantation
- The patient must be able to comprehend and have signed the informed consent
Who cannot join
- Diagnosis of any of the following plasma cell disorders: POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein [M-protein] and skin changes) Non-secretory myeloma (no measurable protein on Serum Free Lite Assay)
- Plasma cell leukemia
- Amyloidosis
- Use of corticosteroids (glucocorticoids) within 21 days of pre-transplant vaccine or bone marrow collection
- Use of any myeloma-specific therapy other than lenalidomide within 21 days of pre-transplant vaccine
- In a complete remission at the time of bone marrow collection
Show all 11Show fewer
- Infection requiring treatment with antibiotics, antifungal, or antiviral agents within seven days of vaccination or bone marrow collection
- Participation in any clinical trial, within four weeks prior to vaccination or bone marrow collection on this trial, which involved an investigational drug or device
- History of malignancy other than multiple myeloma within five years of vaccination or bone marrow collection, except adequately treated basal or squamous cell skin cancer
- Active autoimmune disease (e.g., rheumatoid arthritis, multiple sclerosis, systemic lupus erythematosis) requiring systemic treatment. Hypothyroidism without evidence of Grave's Disease or Hashimoto's thyroiditis is permitted
- Evidence of spinal cord compression at time of transplant
Trial locations and contacts
1 site in 1 country.
United States1 site
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, 21231
About this study
Official title: Randomized Trial of Activated Marrow Infiltrating Lymphocytes Alone or in Conjunction With an Allogeneic GM-CSF-based Myeloma Cellular Vaccine in the Autologous Transplant Setting in Multiple Myeloma
Patient Population: Patients with active myeloma (Stage II/III) that have completed induction therapy and are eligible for an autologous stem cell transplant.
Number of Patients: Will treat a total of 32 evaluable patients in a 1:1 randomization of aMILs vs aMILs plus vaccine. An evaluable patient is defined as one which has received the activated MILs and is at least 6 months post-transplant.
Read more
Study Objectives:
Disease response as determined by the Blade' criteria will be the primary endpoint of the trial at one year.
Additional study endpoints include progression free survival, parameters of T cell reconstitution, anti-tumor immune responses as well as the effect on osteoclastogenesis and clonogenic myeloma precursor cells.
- Conditions
- Multiple Myeloma
- Being tested
- Activated marrow infiltrating lymphocytes, Allogeneic Myeloma Vaccine, Cyclophosphamide, Filgrastim, Leukapheresis
- Keywords
- 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.
Activated marrow infiltrating lymphocytesBiological
Also called MILs, aMILs
Administered on Days 3 and 4.
Allogeneic Myeloma VaccineBiological
Allogeneic granulocyte macrophage colony-stimulating factor (GM-CSF)-based myeloma cellular vaccine. Administered on Days 21, 60, 180, and 300.
CyclophosphamideDrug
Also called Cytoxan
Administered at 2.5 g/m^2.
FilgrastimBiological
Also called G-CSF
Administered post cyclophosphamide daily until leukapheresis.
LeukapheresisProcedure or surgery
Also called Apheresis
Performed approximately 12 days post cyclophosphamide. Exact date depends on peripheral blood CD34+ cell counts.
MelphalanDrug
Also called Alkeran
100 mg/m^2/day given on Days -2 and -1.
Autologous stem cell transplantBiological
Also called ASCT
Infused on Day 0.
| Study group | Role | What they receive |
|---|---|---|
| ASCT + MILs | Experimental | Cyclophosphamide and filgrastim will be given to mobilize peripheral blood stem cells. Leukapheresis will be performed to collect peripheral blood from which activated marrow infiltrating lymphocytes will be produced. A melphalan conditioning regimen will be used prior to autologous stem cell transplant, and the MILs product will be administered on Days 3 and 4. Receives: Biological: Activated marrow infiltrating lymphocytes; Drug: Cyclophosphamide; Biological: Filgrastim; Procedure: Leukapheresis; Drug: Melphalan; Biological: Autologous stem cell transplant |
| ASCT + MILs + vaccine | Experimental | Cyclophosphamide and filgrastim will be given to mobilize peripheral blood stem cells. Leukapheresis will be performed to collect peripheral blood from which activated marrow infiltrating lymphocytes will be produced. A melphalan conditioning regimen will be used prior to autologous stem cell transplant, and the MILs product will be administered on Days 3 and 4. The allogeneic myeloma vaccine will be administered on Days 21, 60, 180, and 300. Receives: Biological: Activated marrow infiltrating lymphocytes; Biological: Allogeneic Myeloma Vaccine; Drug: Cyclophosphamide; Biological: Filgrastim; Procedure: Leukapheresis; Drug: Melphalan; Biological: Autologous stem cell transplant |
What is being measured
The primary outcome is the main question the study is designed to answer.
Response Rates by Blade Criteria
Number of participants with each disease response category utilizing the Blade criteria:
- Complete Response (CR): Defined as negative serum and urine immunofixation and a bone marrow aspirate with < 5% plasma cells.
- Near Complete Response (nCR): Defined as negative serum and urine paraprotein, positive serum and/or urine immunofixation, and a bone marrow aspirate with < 5% plasma cells.
- Very Good Partial Response (VGPR): Defined as negative serum and urine paraprotein with positive serum and/or urine immunofixation; or a 90% decrease in serum paraprotein with urine paraprotein < 100 mg/24 hours.
- Partial Response (PR): Defined as a 50-89% decrease in serum paraprotein.
- Minimal Response (MR): Defined as a 25-49% decrease in serum paraprotein.
- Stable Disease (SD): Defined as not falling into any other response category.
- Overall response rate (ORR): Total of CR, nCR, VGPR, and PR.
Measured: Up to 1 year
Secondary outcomes (10)
Progression-free Survival
Median number of months that participants were alive without disease relapse or progression (progression-free survival).
Measured: Up to 5 years
Overall Survival
Number of participants alive at 5 years (overall survival).
Measured: Up to 5 years
Feasibility as Measured by Participant Withdrawal or Removal
Number of participants who withdrew or were removed from the study for reasons other than lack of efficacy prior to completion.
Measured: Up to 1 year
Safety as Measured by Grade 3-5 Adverse Events
Number of participants who experienced at least one grade 3-5 adverse event by CTCAE 3.0 that was attributed to MILs or the myeloma vaccine.
Measured: Up to 1 year
Anti-tumor Immune Response
- Evaluate tumor specific responses in blood and bone marrow
- Examine T cell responses to DC-pulsed myeloma cell lines
- Examine induction of novel antibody responses
Measured: Days 60, 180, and 360
The Effect of aMILs on Osteoclastogenesis as Measured by Bone Turnover (RANKL/OPG Ratio)
Measured: Days 60, 180, and 360
The Effect of aMILs on Osteoclastogenesis as Measured by Bone Turnover (Serum C Telopeptide Levels)
Serum C Telopeptide
Measured: Days 60, 180, 360
The Effect of aMILs on Osteoclastogenesis as Measured by Bone Turnover (bAlkaline Phosphatase Levels)
bAlkaline phosphatase
Measured: Days 60, 180, 360
The Effect of aMILs on Osteoclastogenesis as Measured by Bone Turnover (Osteocalcin Levels)
Osteocalcin
Measured: Days 60, 180, 360
Effect of aMILs on Clonogenic Myeloma Precursors
- Examine side population of CD19 enriched PBLs throughout study.
Measured: Days 60, 180, and 360
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jan 2010 (estimated)
- Study start15 Jan 2010
- Primary completionDec 2014
- Study completionJun 2020
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.
- Other trials for Multiple MyelomaStudies of the same condition, open and under way.
- More trials run by Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsThe 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 36 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Ivan Borrello, MD, Principal investigator, Johns Hopkins University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01045460
- Sponsor's protocol ID
- J0997
- Other IDs
- NA_00029491
- Acronym
- aMILs
- Status last verified
- Feb 2021
- First submitted
- 14 Dec 2009
- Last updated
- 9 Apr 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Trial of Activated Marrow Infiltrating Lymphocytes Alone or in Conjunction With an Allogeneic GM-CSF-based Myeloma Cellular Vaccine in the Autologous Transplant Setting in Multiple Myeloma
- ClinicalTrials.gov ID
- NCT01045460
- Acronym / sponsor ID
- aMILs / J0997
- Conditions
- Multiple Myeloma
- Keywords
- multiple myeloma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 36 participants (actual)
- Lead sponsor
- Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsUniversity, hospital or other
- Study start
- 15 Jan 2010 (actual)
- Primary completion
- Dec 2014 (actual)
- Study completion
- Jun 2020 (actual)
- First posted
- 11 Jan 2010 (estimated)
- Results
- Posted 8 Oct 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Patient Population: Patients with active myeloma (Stage II/III) that have completed induction therapy and are eligible for an autologous stem cell transplant.
Number of Patients: Will treat a total of 32 evaluable patients in a 1:1 randomization of aMILs vs aMILs plus vaccine. An evaluable patient is defined as one which has received the activated MILs and is at least 6 months post-transplant.
Study Objectives:
Disease response as determined by the Blade' criteria will be the primary endpoint of the trial at one year.
Additional study endpoints include progression free survival, parameters of T cell reconstitution, anti-tumor immune responses as well as the effect on osteoclastogenesis and clonogenic myeloma precursor cells.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ASCT + MILs | Experimental | Biological: Activated marrow infiltrating lymphocytes, Drug: Cyclophosphamide, Biological: Filgrastim, Procedure: Leukapheresis, Drug: Melphalan, Biological: Autologous stem cell transplantCyclophosphamide and filgrastim will be given to mobilize peripheral blood stem cells. Leukapheresis will be performed to collect peripheral blood from which activated marrow infiltrating lymphocytes will be produced. A melphalan conditioning regimen will be used prior to autologous stem cell transplant, and the MILs product will be administered on Days 3 and 4. |
| ASCT + MILs + vaccine | Experimental | Biological: Activated marrow infiltrating lymphocytes, Biological: Allogeneic Myeloma Vaccine, Drug: Cyclophosphamide, Biological: Filgrastim, Procedure: Leukapheresis, Drug: Melphalan, Biological: Autologous stem cell transplantCyclophosphamide and filgrastim will be given to mobilize peripheral blood stem cells. Leukapheresis will be performed to collect peripheral blood from which activated marrow infiltrating lymphocytes will be produced. A melphalan conditioning regimen will be used prior to autologous stem cell transplant, and the MILs product will be administered on Days 3 and 4. The allogeneic myeloma vaccine will be administered on Days 21, 60, 180, and 300. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Durie-Salmon Stage II or III multiple myeloma
- Newly diagnosed either prior to receiving treatment or having completed induction therapy
- Relapsed myeloma not previously transplanted within the past 5 years
- Measurable serum and/or urine M-protein from prior to induction therapy documented and available. A positive serum free lite assay is acceptable
- Age greater than 18 years old
Key exclusion criteria (11 listed)
- Diagnosis of any of the following plasma cell disorders: POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein [M-protein] and skin changes) Non-secretory myeloma (no measurable protein on Serum Free Lite Assay)
- Plasma cell leukemia
- Amyloidosis
- Use of corticosteroids (glucocorticoids) within 21 days of pre-transplant vaccine or bone marrow collection
- Use of any myeloma-specific therapy other than lenalidomide within 21 days of pre-transplant vaccine
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 |
|---|---|---|
| Activated marrow infiltrating lymphocytesAlso: MILs, aMILsAdministered on Days 3 and 4. | Biological | ASCT + MILs, ASCT + MILs + vaccine |
| Allogeneic Myeloma VaccineAllogeneic granulocyte macrophage colony-stimulating factor (GM-CSF)-based myeloma cellular vaccine. Administered on Days 21, 60, 180, and 300. | Biological | ASCT + MILs + vaccine |
| CyclophosphamideAlso: CytoxanAdministered at 2.5 g/m^2. | Drug | ASCT + MILs, ASCT + MILs + vaccine |
| FilgrastimAlso: G-CSFAdministered post cyclophosphamide daily until leukapheresis. | Biological | ASCT + MILs, ASCT + MILs + vaccine |
| LeukapheresisAlso: ApheresisPerformed approximately 12 days post cyclophosphamide. Exact date depends on peripheral blood CD34+ cell counts. | Procedure or surgery | ASCT + MILs, ASCT + MILs + vaccine |
| MelphalanAlso: Alkeran100 mg/m^2/day given on Days -2 and -1. | Drug | ASCT + MILs, ASCT + MILs + vaccine |
| Autologous stem cell transplantAlso: ASCTInfused on Day 0. | Biological | ASCT + MILs, ASCT + MILs + vaccine |
Primary outcome
Response Rates by Blade Criteria
Time frame: Up to 1 year
Number of participants with each disease response category utilizing the Blade criteria: * Complete Response (CR): Defined as negative serum and urine immunofixation and a bone marrow aspirate with < 5% plasma cells. * Near Complete Response (nCR): Defined as negative serum and urine paraprotein, positive serum and/or urine immunofixation, and a bone marrow aspirate with < 5% plasma cells. * Very Good Partial Response (VGPR): Defined as negative serum and urine paraprotein with positive serum and/or urine immunofixation; or a 90% decrease in serum paraprotein with urine paraprotein < 100 mg/24 hours. * Partial Response (PR): Defined as a 50-89% decrease in serum paraprotein. * Minimal Response (MR): Defined as a 25-49% decrease in serum paraprotein. * Stable Disease (SD): Defined as not falling into any other response category. * Overall response rate (ORR): Total of CR, nCR, VGPR, and PR.
10 secondary outcomes
Progression-free Survival
Time frame: Up to 5 years
Overall Survival
Time frame: Up to 5 years
Feasibility as Measured by Participant Withdrawal or Removal
Time frame: Up to 1 year
Safety as Measured by Grade 3-5 Adverse Events
Time frame: Up to 1 year
Anti-tumor Immune Response
Time frame: Days 60, 180, and 360
The Effect of aMILs on Osteoclastogenesis as Measured by Bone Turnover (RANKL/OPG Ratio)
Time frame: Days 60, 180, and 360
The Effect of aMILs on Osteoclastogenesis as Measured by Bone Turnover (Serum C Telopeptide Levels)
Time frame: Days 60, 180, 360
The Effect of aMILs on Osteoclastogenesis as Measured by Bone Turnover (bAlkaline Phosphatase Levels)
Time frame: Days 60, 180, 360
The Effect of aMILs on Osteoclastogenesis as Measured by Bone Turnover (Osteocalcin Levels)
Time frame: Days 60, 180, 360
Effect of aMILs on Clonogenic Myeloma Precursors
Time frame: Days 60, 180, and 360
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Apr 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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.
Ivan Borrello, MD principal investigator
Johns Hopkins University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Activated marrow infiltrating lymphocytes, Allogeneic Myeloma Vaccine and Cyclophosphamide in people with Multiple Myeloma, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins 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 8 inclusion and 11 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 9 Apr 2021. 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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 8 Oct 2019). 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?
Response Rates by Blade Criteria (time frame: Up to 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 9 Apr 2021.