Multiple MyelomaPhase 2NCT02331368
Phase 2 Multi-center Study of Anti-PD-1 During Lymphopenic State After HDT/ASCT for Multiple Myeloma
A Phase 2 study testing Autologous Stem Cell Transplant, Melphalan and Lenalidomide in people with Multiple Myeloma, run by University of Michigan Rogel Cancer Center at 2 sites in United States.
Trial summary
Multiple myeloma (MM) is a common incurable blood cancer causing debilitating symptoms-bone pain, kidney failure, low blood counts and infection. Chemotherapy outcomes are disappointing due to short-term response and long-term toxicities. 1. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Multiple Myeloma
- What is being tested?
- Autologous Stem Cell Transplant, Melphalan and Lenalidomide
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 2 sitesUnited States
- Study dates
- Jun 2015to Jun 2017
- 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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subjects with MM (Multiple Myeloma) of any stage
- Has no Progressive Disease (PD) AND has suboptimal response with primary therapy
- Has measurable disease
- Has no prior hematopoietic stem cell transplant of any type
- Has performance status of 0 or 1 (Eastern Cooperative Oncology, ECOG, Performance Scale)
- Has had a successful peripheral blood stem cell collection with G-CSF (Filgrastim) +/- Plerixafor (Mozobil) only
Show all 12Show fewer
- Be willing and able to provide written informed consent
- Female subjects of child bearing age should have negative urine or serum pregnancy test
- Female subjects of child bearing age must be willing to use 2 methods of birth control or be surgically sterile or abstain from heterosexual activity
- Male subjects must agree to use an adequate method of contraception
- Subject must be able to swallow capsules
- Must demonstrate adequate organ function
Who cannot join
- Has history of repeat infections, amyloidosis, hyperviscosity, plasma cell leukemia, POEMS syndrome, Waldenstrom's macroglobulinemia, non-secretory multiple myeloma, or IgM myeloma
- Has known CNS (Central Nervous System) involvement or history of resolved CNS involvement
- Has an active autoimmune disease or history of autoimmune disease that requires systemic treatment with steroids of immunosuppressive agents.
- Has active, non-infectious pneumonitis
- Has diagnosis of immunosuppressive disorder or on immunosuppressive therapy within 7 days of transplant admission
- Is currently participating in or has previously participated in the study of an investigational drug/device within 4 weeks of transplant admission
Show all 19Show fewer
- Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or CTLA-4
- Has had prior monoclonal antibody, chemotherapy, small molecule therapy, or radiation within 2 weeks of transplant admission
- Has not recovered from adverse events due to previously administered agent
- Must be free of additional malignancy for at least 5 years
- Has an active infection requiring systemic therapy
- Has known psychiatric or substance abuse disorders that would interfere with requirements of the study
- Is pregnant or breastfeeding or expecting to conceive
- Has known HIV, Hepatitis B, or Hepatitis C infection
- Has clinically significant coagulopathy
- Has known symptomatic heart failure, unstable angina pectoris, or cardiac arrhythmia
- Has received any type of hematopoietic cell transplant
- Has received a live vaccine within 30 days of transplant admission
- Is or has an immediate family member whos is investigational site or sponsor staff directly involved with this study
Trial locations and contacts
2 sites in 1 country.
United States2 sites
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, 48109
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
About this study
Official title: Phase 2 Multi-center Study of Anti-Programmed-Death-1 [Anti-PD-1] During Lymphopenic State After High-Dose Chemotherapy and Autologous Hematopoietic Stem Cell Transplant [HDT/ASCT] for Multiple Myeloma
Multiple myeloma (MM) is a common incurable blood cancer causing debilitating symptoms-bone pain, kidney failure, low blood counts and infection. Chemotherapy outcomes are disappointing due to short-term response and long-term toxicities.
- Studies showed these patients have weak immune against MM due to the immune checkpoint mediated by the PD1/PD-L1 interaction between immune cells and MM. Anti-PD-1 antibody (anti-PD1) disrupts this interaction, thus unleashing immune cell function and leading to killing of MM cells.
- Studies further showed enhancement of this "unleash" after autologous transplant and better MM control by anti-PD1 when used after transplant.
- Anti-PD1 has been extensively studied in patients with other cancers. It is very safe and effective and has been FDA-approved. Complications are of mild degree and easy to manage successfully in out-patient setting. Severe complications are rare.
Thus, investigators proposed an efficacy study of anti-PD1 treatment after transplant to improve MM treatment outcomes. This was a collaborative study with Medical College of Wisconsin (headquarter of Center for International blood and Marrow Transplant Research). Investigators hypothesized that anti-PD1 treatment would increase the MM response and the MM control duration when added to the standard MM treatment after transplant. Anti-PD1 was given at the dose and interval, which had been studied previously (200 mg intravenous injection every 3 weeks) between 2 weeks until 6 months after transplant. Subjects were monitored closely during and after anti-PD1 therapy until at least 1 year post transplant. Late complications were followed for 3 years.
- Conditions
- Multiple Myeloma
- Being tested
- Autologous Stem Cell Transplant, Melphalan, Lenalidomide, MK-3475
- Keywords
- Multiple Myeloma, Anti-PD-1, Pembrolizumab, Post-transplant, Maintenance
- Medical subject headings
- Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Autologous Stem Cell TransplantProcedure or surgery
MelphalanDrug
140-200 mg/m^2
LenalidomideDrug
5-15 mg/day starting 45-90 days post-transplant
MK-3475Drug
Also called Anti-PD-1, Pembrolizumab
200 mg/day every 3 weeks starting day +14 post-transplant for a total of 9 doses.
| Study group | Role | What they receive |
|---|---|---|
| Anti-PD-1 (MK-3475) | Experimental | Standard Treatment:
High-dose Melphalan and autologous stem cell transplantation with post-transplant maintenance of Lenalidomide.
Study Treatment:
200 mg/day of MK-3475 administered every 3 weeks, starting day +14 post-transplant for a total of 9 doses. Receives: Procedure: Autologous Stem Cell Transplant; Drug: Melphalan; Drug: Lenalidomide; Drug: MK-3475 |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Number of Patients That Achieve Complete Response
The primary efficacy endpoint is complete response rate. The complete response rate was estimated by the observed proportion of complete responders at day 180. Complete response (CR) was defined as negative immunofixation of serum and urine and disappearance of any soft tissue plasmacytomas, and <5% plasma cells in bone marrow and negative bone marrow flow cytometry.
Measured: 180 days post-transplant
Secondary outcomes (2)
The Estimated Percentage of Patients Alive Without Relapse or Progression at 2 Years
Progression is defined as an increase of ≥ 25% from the lowest response value in any one or more of the following:
Serum M-component with an absolute increase ≥ 0.5 g/dL; and/or Urine M-component with an absolute increase ≥ 200 mg/24 hours; and/or Only in patients without measurable serum and urine M-protein levels: the difference between involved and uninvolved FLC levels (absolute increase must be >100mg/l) Bone marrow plasma cell percentage (absolute % must be ≥10% Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas Development of hypercalcemia (corrected serum calcium >11.5mg/100ml) that can be attributed solely to the plasma cell proliferative disorder
Measured: 2 Years
The Estimated Percentage of Patients Alive at 2 Years
Measured: 2 Years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jan 2015 (estimated)
- Study startJun 2015
- Primary completionJun 2017
- Study completionJun 2017
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 University of Michigan Rogel Cancer CenterThe 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Michigan Rogel Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Medical College of Wisconsin
- Responsible party
- Sponsor
- Investigators
- Attaphol Pawarode, M.D., Principal investigator, University of Michigan Rogel Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02331368
- Sponsor's protocol ID
- UMCC 2014.134
- Status last verified
- Jul 2018
- First submitted
- 2 Jan 2015
- Last updated
- 27 Jul 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
D'Souza A, Hari P, Pasquini M, Braun T, Johnson B, Lundy S, Couriel D, Hamadani M, Magenau J, Dhakal B, Shah NN, Riwes M, Parkin B, Reddy P, Pawarode A. A Phase 2 Study of Pembrolizumab during Lymphodepletion after Autologous Hematopoietic Cell Transplantation for Multiple Myeloma. Biol Blood Marrow Transplant. 2019 Aug;25(8):1492-1497. doi: 10.1016/j.bbmt.2019.04.005. Epub 2019 Apr 6.
PubMed 30959163
Study at a glance
From the registry record, last updated by the sponsor on 27 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 2 Multi-center Study of Anti-Programmed-Death-1 [Anti-PD-1] During Lymphopenic State After High-Dose Chemotherapy and Autologous Hematopoietic Stem Cell Transplant [HDT/ASCT] for Multiple Myeloma
- ClinicalTrials.gov ID
- NCT02331368
- Acronym / sponsor ID
- UMCC 2014.134
- Conditions
- Multiple Myeloma
- Keywords
- Multiple Myeloma, Anti-PD-1, Pembrolizumab, Post-transplant, Maintenance
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- University of Michigan Rogel Cancer CenterUniversity, hospital or other
- Collaborators
- Medical College of Wisconsin
- Study start
- Jun 2015
- Primary completion
- Jun 2017 (actual)
- Study completion
- Jun 2017 (actual)
- First posted
- 6 Jan 2015 (estimated)
- Results
- Posted 27 Jul 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Multiple myeloma (MM) is a common incurable blood cancer causing debilitating symptoms-bone pain, kidney failure, low blood counts and infection. Chemotherapy outcomes are disappointing due to short-term response and long-term toxicities.
- Studies showed these patients have weak immune against MM due to the immune checkpoint mediated by the PD1/PD-L1 interaction between immune cells and MM. Anti-PD-1 antibody (anti-PD1) disrupts this interaction, thus unleashing immune cell function and leading to killing of MM cells.
- Studies further showed enhancement of this "unleash" after autologous transplant and better MM control by anti-PD1 when used after transplant.
- Anti-PD1 has been extensively studied in patients with other cancers. It is very safe and effective and has been FDA-approved. Complications are of mild degree and easy to manage successfully in out-patient setting. Severe complications are rare.
Thus, investigators proposed an efficacy study of anti-PD1 treatment after transplant to improve MM treatment outcomes. This was a collaborative study with Medical College of Wisconsin (headquarter of Center for International blood and Marrow Transplant Research). Investigators hypothesized that anti-PD1 treatment would increase the MM response and the MM control duration when added to the standard MM treatment after transplant. Anti-PD1 was given at the dose and interval, which had been studied previously (200 mg intravenous injection every 3 weeks) between 2 weeks until 6 months after transplant. Subjects were monitored closely during and after anti-PD1 therapy until at least 1 year post transplant. Late complications were followed for 3 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Anti-PD-1 (MK-3475) | Experimental | Procedure: Autologous Stem Cell Transplant, Drug: Melphalan, Drug: Lenalidomide, Drug: MK-3475Standard Treatment: High-dose Melphalan and autologous stem cell transplantation with post-transplant maintenance of Lenalidomide. Study Treatment: 200 mg/day of MK-3475 administered every 3 weeks, starting day +14 post-transplant for a total of 9 doses. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Subjects with MM (Multiple Myeloma) of any stage
- Has no Progressive Disease (PD) AND has suboptimal response with primary therapy
- Has measurable disease
- Has no prior hematopoietic stem cell transplant of any type
- Has performance status of 0 or 1 (Eastern Cooperative Oncology, ECOG, Performance Scale)
Key exclusion criteria (19 listed)
- Has history of repeat infections, amyloidosis, hyperviscosity, plasma cell leukemia, POEMS syndrome, Waldenstrom's macroglobulinemia, non-secretory multiple myeloma, or IgM myeloma
- Has known CNS (Central Nervous System) involvement or history of resolved CNS involvement
- Has an active autoimmune disease or history of autoimmune disease that requires systemic treatment with steroids of immunosuppressive agents.
- Has active, non-infectious pneumonitis
- Has diagnosis of immunosuppressive disorder or on immunosuppressive therapy within 7 days of transplant admission
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 |
|---|---|---|
| Autologous Stem Cell Transplant | Procedure or surgery | Anti-PD-1 (MK-3475) |
| Melphalan140-200 mg/m^2 | Drug | Anti-PD-1 (MK-3475) |
| Lenalidomide5-15 mg/day starting 45-90 days post-transplant | Drug | Anti-PD-1 (MK-3475) |
| MK-3475Also: Anti-PD-1, Pembrolizumab200 mg/day every 3 weeks starting day +14 post-transplant for a total of 9 doses. | Drug | Anti-PD-1 (MK-3475) |
Primary outcome
The Number of Patients That Achieve Complete Response
Time frame: 180 days post-transplant
The primary efficacy endpoint is complete response rate. The complete response rate was estimated by the observed proportion of complete responders at day 180. Complete response (CR) was defined as negative immunofixation of serum and urine and disappearance of any soft tissue plasmacytomas, and <5% plasma cells in bone marrow and negative bone marrow flow cytometry.
2 secondary outcomes
The Estimated Percentage of Patients Alive Without Relapse or Progression at 2 Years
Time frame: 2 Years
The Estimated Percentage of Patients Alive at 2 Years
Time frame: 2 Years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jul 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 30959163D'Souza A, Hari P, Pasquini M, Braun T, Johnson B, Lundy S, Couriel D, Hamadani M, Magenau J, Dhakal B, Shah NN, Riwes M, Parkin B, Reddy P, Pawarode A. A Phase 2 Study of Pembrolizumab during Lymphodepletion after Autologous Hematopoietic Cell Transplantation for Multiple Myeloma. Biol Blood Marrow Transplant. 2019 Aug;25(8):1492-1497. doi: 10.1016/j.bbmt.2019.04.005. Epub 2019 Apr 6.
Related trials for Multiple Myeloma
Not yet recruitingPhase 2
Study of YKST02 in Adults With Relapsed or Refractory Multiple Myeloma
Relapsed or Refractory Multiple Myeloma (RRMM)
RecruitingPhase 2
Engaging T-cells to Eliminate MRD in Newly Diagnosed Myeloma Optimizing Response With Talquetmab and Teclistamab (ROTATE)
Multiple Myeloma
Active, not recruitingPhase 3
A Phase III Study of Eque-cel in Subjects With Len-refractory RRMM (FUMANBA-03)
Multiple Myeloma
Active, not recruitingPhase 1/2
A Window of Opportunity Trial to Learn if Linvoseltamab is Safe and Well Tolerated, and How Well it Works in Adult Participants With Recently Diagnosed Multiple Myeloma Who Have Not Already Received Treatment
Multiple Myeloma
Active, not recruitingPhase 2
Testing AZD5363 as a Potential Targeted Treatment in Cancers With AKT Genetic Changes (MATCH-Subprotocol Y)
Advanced Lymphoma, Advanced Malignant Solid Neoplasm
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.
Attaphol Pawarode, M.D. principal investigator
University of Michigan Rogel Cancer Center
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Autologous Stem Cell Transplant, Melphalan and Lenalidomide in people with Multiple Myeloma, run by University of Michigan Rogel Cancer Center at 2 sites 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 12 inclusion and 19 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 27 Jul 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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 27 Jul 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?
The Number of Patients That Achieve Complete Response (time frame: 180 days post-transplant). 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 NCT02331368, 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 27 Jul 2018.