Multiple Myeloma and Plasma Cell NeoplasmPhase 1/2NCT00566098
Activated White Blood Cells With ASCT for Newly Diagnosed Multiple Myeloma
A Phase 1/2 study testing MILs, Melphalan and PCV13 in people with Multiple Myeloma and Plasma Cell Neoplasm, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 1 site in United States.
Trial summary
RATIONALE: Activating white blood cells in the laboratory may help them kill more cancer cells when they are put back in the body. This may be an effective treatment for patients undergoing a stem cell transplant for multiple myeloma. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Multiple Myeloma and Plasma Cell Neoplasm
- What is being tested?
- MILs, Melphalan and PCV13
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 26 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2007to Oct 2018
- Phase
- Phase 1/2
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
DISEASE CHARACTERISTICS:
- Diagnosis of multiple myeloma
- Newly diagnosed disease
- Durie-Salmon stage II or III disease
- Measurable disease, defined by any of the following:
- Measurable serum and/or urine M-protein levels documented and available prior to induction therapy
- Positive serum free light chain assay
- Must have completed a minimum of 3 courses of myeloma specific therapy
- Candidate for autologous stem cell transplantation
- Patients who have achieved a complete remission at the time of bone marrow harvest for marrow infiltrating lymphocytes (MILs) expansion are not eligible
- No evidence of spinal cord compression
- Diagnosis of the following cancers are not allowed:
- POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein and skin changes)
- Non-secretory myeloma (no measurable protein on serum free light chain assay)
- Plasma cell leukemia
- No amyloidosis
PATIENT CHARACTERISTICS:
- ECOG performance status 0-2
- Life expectancy ≥ 6 months
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and up to day 180
- Corrected serum calcium < 11 mg/dL and no evidence of symptomatic hypercalcemia
- Total bilirubin ≤ 2.0 times upper limit of normal (ULN)
- ALT ≤ 2.0 times ULN
- Serum creatinine < 2.0 mg/dL
- No history of other malignancy within the past 5 years, except adequately treated basal cell or squamous cell skin cancer
- No history of autoimmune disease (e.g., rheumatoid arthritis, multiple sclerosis, systemic lupus erythematosus) requiring systemic treatment
- Hypothyroidism without evidence of Graves' disease or Hashimoto thyroiditis is allowed
- No infection requiring treatment with antibiotics, antifungal, or antiviral agents within the past 7 days
- No HIV infection
- No major organ system dysfunction including, but not limited to, the following:
- New York Heart Association class III or IV congestive heart failure
- Pulmonary disease requiring the use of inhaled steroids or bronchodilators
- Renal, hepatic, gastrointestinal, neurologic, or psychiatric dysfunction that would impair ability to participate in the study
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- No prior hematopoietic stem cell transplantation
- At least 3 weeks since prior corticosteroids (i.e., glucocorticoids)
- At least 3 weeks since prior myeloma-specific therapy
- At least 4 weeks since participation in any clinical trial that involved an investigational drug or device
- No concurrent therapy with any of the following:
- Corticosteroids (e.g., hydrocortisone, prednisone, prednisolone, dexamethasone [Decadron])
- Inhaled steroids used for treatment of allergic rhinitis or pulmonary disease allowed
- Thalidomide
- Interferon
- Growth factors, interleukins, or other cytokines (except filgrastim [G-CSF] as outlined in the protocol, or erythropoietin)
- Cytotoxic chemotherapy agents (except cyclophosphamide for stem cell mobilization and high-dose melphalan)
- Immunosuppressive drugs
- Experimental therapies
- Radiotherapy
Trial locations and contacts
1 site in 1 country.
United States1 site
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, 21231-2410
About this study
Official title: Adoptive Immunotherapy Utilizing Activated Marrow Infiltrating Lymphocytes in the Autologous Transplant Setting in Multiple Myeloma
RATIONALE: Activating white blood cells in the laboratory may help them kill more cancer cells when they are put back in the body. This may be an effective treatment for patients undergoing a stem cell transplant for multiple myeloma.
PURPOSE: This phase I/II trial is studying the side effects of activated white blood cells and to see how well they work in treating patients who are undergoing a stem cell transplant for newly diagnosed stage II or stage III multiple myeloma.
Read the detailed description
OBJECTIVES:
Primary
- Evaluate the safety and response rate of activated marrow infiltrating lymphocytes (aMILs) in patients undergoing autologous peripheral blood stem cell transplantation for newly diagnosed, stage II-III multiple myeloma.
- Determine the overall in vitro fold-expansion and assess pre- and post-expansion for myeloma T-cell specificity in assessing the feasibility of generating aMILs from myeloma patients.
- Assess the toxicity of aMILs.
- Evaluate the effect of aMILs on hematopoietic engraftment, including neutrophil engraftment, platelet engraftment, and primary graft failure (if failure occurs).
- Evaluate response rates utilizing the Blade criteria, including the complete response (CR) rate, near complete response (nCR) rate, very good partial response (VGPR) rate, partial response (PR) rate, minimal response (MR) rate, and overall response rate (CR, VGPR, PR, MR).
Secondary
- Evaluate T-cell reconstitution, including absolute lymphocyte counts, CD3+, CD4+, and CD8+ T-cell counts.
- Evaluate progression-free survival and overall survival.
- Evaluate anti-tumor immune response.
- Determine pneumococcal-specific vaccine responses.
- Determine delayed-type hypersensitivity (DTH) responses.
OUTLINE: Patients undergo collection of marrow infiltrating lymphocytes (MILs)* either at diagnosis prior to the initiation of induction therapy or upon completion of induction therapy. The MILs bone marrow product undergo ex vivo activation and expansion of T cells for 7-8 days to produce activated marrow infiltrating lymphocytes (aMILs). Patients then undergo stem cell mobilization and leukapheresis to collect the peripheral blood stem cells 12 days after mobilization. Patients receive melphalan IV over 20-30 minutes on days -2 and -1 and undergo a peripheral blood stem cell transplantation on day 0 as planned. Patients receive aMILs infusion on day 3. Patients receive pneumococcal polyvalent vaccine on day 21.
NOTE: *Patients who have completed induction therapy receive pneumococcal polyvalent vaccine approximately 2 weeks prior to MILs collection; patients undergoing MILs collection prior to starting induction therapy do not receive a pre-transplantation vaccine.
Blood and bone marrow samples are collected periodically for laboratory correlative studies.
After completion of study treatment, patients are followed periodically for up to 1 year.
- Being tested
- MILs, Melphalan, PCV13
- Keywords
- stage II multiple myeloma, stage III multiple myeloma
- Medical subject headings
- Multiple Myeloma, Neoplasms, Plasma Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MILsBiological
Also called Marrow infiltrating lymphocytes, Activated marrow infiltrating lymphocytes, aMILs
MelphalanDrug
Also called Alkeran
PCV13Biological
Also called Prevnar
| Study group | Role | What they receive |
|---|---|---|
| ASCT+MILs | Experimental | Autologous stem cell transplant with a conditioning regimen of melphalan 100 mg/m^2 on each of Days -2 and -1. Infusion of activated marrow infiltrating lymphocytes (MILs) on Day 3. PCV13 vaccine will be given before and/or after Day 0 depending on when participants are enrolled. Receives: Biological: MILs; Drug: Melphalan; Biological: PCV13 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Hematopoietic Engraftment
Days to absolute neutrophil count > 500 cells per microliter.
Measured: Up to 1 year
Disease Response
Percentage of participants with partial or complete response by Bladé criteria. Partial response is defined as a >= 50% decrease in serum paraprotein or 90% decrease in urinary light chains (for participants without measurable serum paraprotein). Complete response is defined as negative serum and urine immunofixation and a bone marrow aspirate with < 5% plasma cells.
Measured: Up to 2 years
Feasibility of MILs Generation as Assessed by Percentage of Participants With Successful MIL Generation
Success rate of expanding MILs in vitro and obtaining a protocol-specified product.
Measured: Up to 1 year
Secondary outcomes (4)
T-cell Reconstitution as Determined by Absolute Lymphocyte Count (ALC)
ALC counts trending over time.
Measured: Days 14, 28, 60, 180, and 360
Survival
Survival in months for participants who are alive (Overall Survival) and alive without disease progression (Progression-free survival). Disease progression is defined as a change from negative to positive on immunofixation or electrophoresis for participants previously in complete remission or a 25% increase in serum electrophoresis for participants not previously in complete remission. Partial response is defined as a >= 50% decrease in serum paraprotein or 90% decrease in urinary light chains (for participants without measurable serum paraprotein). Complete response is defined as negative serum and urine immunofixation and a bone marrow aspirate with < 5% plasma cells.
Measured: Up to 129 months
Pneumococcal-specific Vaccine Responses
CRM-197 Prevnar-specific vaccine responses that measure the T-cell response of the vaccine quantified as %CD3+/CFSE-low/IFN-gamma+.
Measured: At time of bone marrow harvest, Day 60 post-transplant, Day 180 post-transplant, and Day 360 post-transplant
Anti-tumor Immune Responses
Myeloma lysate response that measures the T-cell response quantified as %CD3+/CFSE-low/IFN-gamma+.
Measured: At time of bone marrow harvest, Day 60 post-transplant, Day 180 post-transplant, and Day 360 post-transplant
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Dec 2007 (estimated)
- Study startNov 2007
- Primary completionJun 2014
- Study completionOct 2018
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 Myeloma and Plasma Cell NeoplasmStudies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Ivan Borrello, MD, Study chair, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00566098
- Sponsor's protocol ID
- J0770
- Other IDs
- P30CA006973, NA_00012038
- Status last verified
- May 2023
- First submitted
- 30 Nov 2007
- Last updated
- 26 May 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Individual data sharing
- No
Publications
Noonan KA, Huff CA, Davis J, Lemas MV, Fiorino S, Bitzan J, Ferguson A, Emerling A, Luznik L, Matsui W, Powell J, Fuchs E, Rosner GL, Epstein C, Rudraraju L, Ambinder RF, Jones RJ, Pardoll D, Borrello I. Adoptive transfer of activated marrow-infiltrating lymphocytes induces measurable antitumor immunity in the bone marrow in multiple myeloma. Sci Transl Med. 2015 May 20;7(288):288ra78. doi: 10.1126/scitranslmed.aaa7014.
PubMed 25995224
Study at a glance
From the registry record, last updated by the sponsor on 26 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Adoptive Immunotherapy Utilizing Activated Marrow Infiltrating Lymphocytes in the Autologous Transplant Setting in Multiple Myeloma
- ClinicalTrials.gov ID
- NCT00566098
- Acronym / sponsor ID
- J0770
- Keywords
- stage II multiple myeloma, stage III multiple myeloma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 26 participants (actual)
- Lead sponsor
- Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Nov 2007 (actual)
- Primary completion
- Jun 2014 (actual)
- Study completion
- Oct 2018 (actual)
- First posted
- 3 Dec 2007 (estimated)
- Results
- Posted 19 Dec 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
RATIONALE: Activating white blood cells in the laboratory may help them kill more cancer cells when they are put back in the body. This may be an effective treatment for patients undergoing a stem cell transplant for multiple myeloma.
PURPOSE: This phase I/II trial is studying the side effects of activated white blood cells and to see how well they work in treating patients who are undergoing a stem cell transplant for newly diagnosed stage II or stage III multiple myeloma.
Detailed description
OBJECTIVES:
Primary
- Evaluate the safety and response rate of activated marrow infiltrating lymphocytes (aMILs) in patients undergoing autologous peripheral blood stem cell transplantation for newly diagnosed, stage II-III multiple myeloma.
- Determine the overall in vitro fold-expansion and assess pre- and post-expansion for myeloma T-cell specificity in assessing the feasibility of generating aMILs from myeloma patients.
- Assess the toxicity of aMILs.
- Evaluate the effect of aMILs on hematopoietic engraftment, including neutrophil engraftment, platelet engraftment, and primary graft failure (if failure occurs).
- Evaluate response rates utilizing the Blade criteria, including the complete response (CR) rate, near complete response (nCR) rate, very good partial response (VGPR) rate, partial response (PR) rate, minimal response (MR) rate, and overall response rate (CR, VGPR, PR, MR).
Secondary
- Evaluate T-cell reconstitution, including absolute lymphocyte counts, CD3+, CD4+, and CD8+ T-cell counts.
- Evaluate progression-free survival and overall survival.
- Evaluate anti-tumor immune response.
- Determine pneumococcal-specific vaccine responses.
- Determine delayed-type hypersensitivity (DTH) responses.
OUTLINE: Patients undergo collection of marrow infiltrating lymphocytes (MILs)* either at diagnosis prior to the initiation of induction therapy or upon completion of induction therapy. The MILs bone marrow product undergo ex vivo activation and expansion of T cells for 7-8 days to produce activated marrow infiltrating lymphocytes (aMILs). Patients then undergo stem cell mobilization and leukapheresis to collect the peripheral blood stem cells 12 days after mobilization. Patients receive melphalan IV over 20-30 minutes on days -2 and -1 and undergo a peripheral blood stem cell transplantation on day 0 as planned. Patients receive aMILs infusion on day 3. Patients receive pneumococcal polyvalent vaccine on day 21.
NOTE: *Patients who have completed induction therapy receive pneumococcal polyvalent vaccine approximately 2 weeks prior to MILs collection; patients undergoing MILs collection prior to starting induction therapy do not receive a pre-transplantation vaccine.
Blood and bone marrow samples are collected periodically for laboratory correlative studies.
After completion of study treatment, patients are followed periodically for up to 1 year.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| ASCT+MILs | Experimental | Biological: MILs, Drug: Melphalan, Biological: PCV13Autologous stem cell transplant with a conditioning regimen of melphalan 100 mg/m^2 on each of Days -2 and -1. Infusion of activated marrow infiltrating lymphocytes (MILs) on Day 3. PCV13 vaccine will be given before and/or after Day 0 depending on when participants are enrolled. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
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 |
|---|---|---|
| MILsAlso: Marrow infiltrating lymphocytes, Activated marrow infiltrating lymphocytes, aMILs | Biological | ASCT+MILs |
| MelphalanAlso: Alkeran | Drug | ASCT+MILs |
| PCV13Also: Prevnar | Biological | ASCT+MILs |
Primary outcome
Hematopoietic Engraftment
Time frame: Up to 1 year
Days to absolute neutrophil count > 500 cells per microliter.
Disease Response
Time frame: Up to 2 years
Percentage of participants with partial or complete response by Bladé criteria. Partial response is defined as a >= 50% decrease in serum paraprotein or 90% decrease in urinary light chains (for participants without measurable serum paraprotein). Complete response is defined as negative serum and urine immunofixation and a bone marrow aspirate with < 5% plasma cells.
Feasibility of MILs Generation as Assessed by Percentage of Participants With Successful MIL Generation
Time frame: Up to 1 year
Success rate of expanding MILs in vitro and obtaining a protocol-specified product.
4 secondary outcomes
T-cell Reconstitution as Determined by Absolute Lymphocyte Count (ALC)
Time frame: Days 14, 28, 60, 180, and 360
Survival
Time frame: Up to 129 months
Pneumococcal-specific Vaccine Responses
Time frame: At time of bone marrow harvest, Day 60 post-transplant, Day 180 post-transplant, and Day 360 post-transplant
Anti-tumor Immune Responses
Time frame: At time of bone marrow harvest, Day 60 post-transplant, Day 180 post-transplant, and Day 360 post-transplant
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 May 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 25995224Noonan KA, Huff CA, Davis J, Lemas MV, Fiorino S, Bitzan J, Ferguson A, Emerling A, Luznik L, Matsui W, Powell J, Fuchs E, Rosner GL, Epstein C, Rudraraju L, Ambinder RF, Jones RJ, Pardoll D, Borrello I. Adoptive transfer of activated marrow-infiltrating lymphocytes induces measurable antitumor immunity in the bone marrow in multiple myeloma. Sci Transl Med. 2015 May 20;7(288):288ra78. doi: 10.1126/scitranslmed.aaa7014.
- 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 study chair
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing MILs, Melphalan and PCV13 in people with Multiple Myeloma and Plasma Cell Neoplasm, 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?
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 May 2023. 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 19 Dec 2018). 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?
Hematopoietic Engraftment (time frame: Up to 1 year). The study lists 3 primary outcomes in all. 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 NCT00566098, 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 May 2023.