Multiple MyelomaPhase 2NCT04558931
Clinical Trial for Autologus NK Cells Alone or in Combination With Isatuximab as Maintenance for Multiple Myeloma
A Phase 2 study testing CellProtect and Isatuximab in people with Multiple Myeloma, run by Karolinska Institutet at 1 site in Sweden.
Trial summary
Prospective, single center, randomized, open label, parallel group, 2-arm study assessing the clinical benefit in term of enhancement of overall response rate of Isatuximab in combination with CellProtect as compared to Isatuximab for the treatment of patients with newly diagnosed multiple myeloma who are eligible for… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Multiple Myeloma
- What is being tested?
- CellProtect and Isatuximab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 62 participants
- Where
- 1 siteSweden
- Study dates
- 2 Jun 2021to 31 Dec 2032
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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
Who may be able to join
- I1. Active multiple myeloma, as defined by the IMWG criteria.
- I2. Evidence of measurable disease:
- I3. Serum monoclonal (M)-protein ≥1.0 g/dL measured using serum protein immunoelectrophoresis a.and/or I4. Urine M-protein ≥200 mg/24 hours measured using urine protein immunoelectrophoresis
- and/or I5. in patients without measurable M protein in serum or urine as per previous criteria, serum immunoglobulin free light chain (sFLC) ≥10 mg/dL and abnormal serum immunoglobulin kappa lambda free light chain ratio <0.26 or >1.65.
- I6. Patients who are newly diagnosed and considered for high-dose chemotherapy I7. Patient has given voluntary written informed consent before performance of any study related procedures not part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to his/her medical care.
- I8. ≥18 years of age (and satisfying the legal age of consent in the jurisdiction in which the study is taking place) I9. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1 I10. Male or Female
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- Male participants A male participant must agree to use contraception of this protocol during the intervention period and for at least 5 months after the last dose of study treatment and refrain from donating sperm during this period.
- Female participants
- A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
- Not a Females of childbearing potential (FCBP), OR A FCBP who must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL within 10 - 14 days prior to and again within 24 hours of starting study medication and must either commit to continue abstinence from heterosexual intercourse or apply a highly effective method of birth control until at least 5 months after last dose of study treatment
- Screening #2 (Conducted after HDT):
- Inclusion criteria as for first screening in addition to response evaluation (at least partial remission must be met).
Who cannot join
- E1. Prior or concurrent exposure to NK cells and NK like T cells, or Approved or investigational treatments for MM.
- E2. Received any investigational drug within 14 days or 5 half-lives of the investigational drug, whichever is longer.
- E3. Diagnosis of primary amyloidosis, monoclonal gammopathy of undetermined significance, or smoldering multiple myeloma (asymptomatic multiple myeloma with absence of related organ or tissue impairment end organ damage).
- E4. Diagnosis of Waldenström's disease, or other conditions in which IgM M-protein is present in the absence of a clonal plasma cell infiltration with lytic bone lesions.
- E5. Prior or current systemic therapy, or SCT for symptomatic multiple myeloma, with the exception of an emergency use of a short course (equivalent of dexamethasone 40 mg/day for 4 days) of corticosteroids, if completed within 14 days prior to randomization.
- E6. Concomitant plasma cell leukemia. E7. Any major procedure within 14 days before the initiation of the study treatment: plasmapheresis, major surgery (kyphoplasty is not considered a major procedure), radiotherapy (except if palliative intent).
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- E8. ECOG PS >2. E9. Hemoglobin <8 g/dL. E10. Platelets <70 × 109/L if <50% of bone marrow (BM) nucleated cells are plasma cells, and ≤30 × 109/L if ≥50% of BM nucleated cells are plasma cells. Platelet transfusion is not allowed within 3 days before the screening haematological test.
- E11. Total bilirubin >1.5 × upper limit of normal (ULN), except for known Gilbert syndrome.
- E12. Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) >3 × ULN.
- E13. Hypersensitivity (or contraindication) to dexamethasone, sucrose histidine (as base and hydrochloride salt), boron, mannitol, and polysorbate 80 or any of the components of study therapy that are not amenable to premedication with steroids, pregelatinized starch, sodium stearyl fumarate, arginine hydrochloride, poloxamer 188, sucrose or any of the other components of study therapy that are not amenable to premedication with steroids and H2 blockers or would prohibit further treatment with these agents.
- E14. Any of the following within 6 months prior to randomization:
- E15. Second/third degree heart block E16. Poorly controlled hypertension E17. Myocardial infarction E18. Severe/unstable angina pectoris E19. Coronary/peripheral artery bypass graft E20. New York Heart Association class III or IV congestive heart failure E21. Grade ≥3 arrhythmias E22. Stroke or transient ischemic attack. E23. Left-ventricular ejection fraction <40%. E24. Prior malignancy. Adequately treated basal cell or squamous cell skin, or superficial (pTis, pTa, and pT1) bladder cancer, or low risk prostate cancer, or any in situ malignancy after curative therapy are allowed, as well as any other cancer for which cytotoxic chemotherapy has been completed ≥3 years prior to enrolment and from which the patient has been disease-free for ≥3 years.
- E25. Known acquired immunodeficiency syndrome (AIDS)-related illness or known HIV disease requiring antiviral treatment or active hepatitis A (defined as positive HA antigen), B (defined as either positive HBs antigen or negative HBs antigen with positive HBc antibody), or C infection (defined as a known positive hepatitis C antibody result and known quantitative hepatitis C (HCV) ribonucleic acid (RNA) results greater than the lower limits of detection of the assay).
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Sweden1 site, 1 recruiting
- Recruiting
Karolinska University Hospital, Huddinge
Stockholm, 17177
Johan Lund, M.D.
Johan Lund, M.D.
About this study
Official title: An Open, Randomised, Controlled, Phase II Trial of CellProtect in Combination With Isatuximab Antibody Versus Isatuximab Antibody Alone as Maintenance Treatment in Patients With Multiple Myeloma Undergoing High Dose Treatment
Prospective, single center, randomized, open label, parallel group, 2-arm study assessing the clinical benefit in term of enhancement of overall response rate of Isatuximab in combination with CellProtect as compared to Isatuximab for the treatment of patients with newly diagnosed multiple myeloma who are eligible for stem cell transplantation (SCT) as maintenance after SCT.
- Conditions
- Multiple Myeloma
- Being tested
- CellProtect, Isatuximab
- Keywords
- NK cells, Consolidation, Isatuximab, SAR650984
- Medical subject headings
- Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CellProtectDrug
Also called Autologous NK cell
In vitro expanded and activated autologous NK cells
IsatuximabDrug
Also called Sarclisa
Naked immunoglobulin (Ig) G1 monoclonal antibody (mAb) that selectively binds to the human cell surface antigen molecule classified as cluster of differentiation (CD) 38
| Study group | Role | What they receive |
|---|---|---|
| A - Isatuximab/CellProtect | Experimental | Isatuximab will be given intravenously (IV) at the dose of 10 mg/kg on Days 1, 8, 15, 22 (cycle 1), 36, 50 (cycle 2), 64, 78 (cycle 3) and monthly thereafter (cycles 4-36).
CellProtect will be given IV infusion at the dose of 3x10^7 cells/kg day 29 , 43 and 3-10x10^7 on day 57.
Each cycle will be 28 days, after completion of third cycles, patients will continue with Isatuximab alone until disease progression, unacceptable AE, death, completion of 3 years of treatment or patient's decision to discontinue, whichever occurs first. Receives: Drug: CellProtect; Drug: Isatuximab |
| B - Isatuximab | Active comparator | Isatuximab will be given intravenously (IV) at the dose of 10 mg/kg on Days 1, 8, 15, 22 (cycle 1), 36, 50 (cycle 2), 64, 78 (cycle 3) and monthly thereafter (cycles 4-36).
Each cycle will be 28 days, after completion of third cycles, patients will continue with Isatuximab alone until disease progression, unacceptable AE, death, completion of 3 years of treatment or patient's decision to discontinue, whichever occurs first. Receives: Drug: Isatuximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall response rate as the occurrence of very good partial response or better after maintenance start
Evaluate in both arms the occurance after maintenance start of: Very good partial response (VGPR) or better rate, as defined by the International Myeloma Working Group (IMWG) criteria.
Measured: From date of first treatment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 96 months
Change in minimal residual disease (MRD) negativity rate
Assessment of changes in MRD negativity rate in patients with complete and very good partial response as well as conversion of MRD positivity to MRD negativity.
Measured: Before start of maintenance, after first Isatuximab cycle, before start of 4th Isatuximab cycle and at 12 and 24 months after start of maintenance
Secondary outcomes (5)
adverse events
Assessment of treatment-emergent adverse events/serious adverse events (TEAEs/SAEs) (including IARs), laboratory parameters, vital signs, weight, ECOG PS, and findings from physical examination. TEAEs are defined as AEs that develop, worsen (according to the Investigator opinion), or become serious during the treatment period.
Measured: From first dose of study treatment up to 30 days after the last dose of study treatment or initiation of further anti-myeloma therapy, whichever occurs first, assessed up to 96 months
Time to progression
The time from randomization to the date of first documentation of PD (as determined by the IRC using the IMWG criteria
Measured: From date of first treatment until date of first documented progression, date of further anti-myeloma therapy or date of death from any cause, whichever came first, assessed up to 96 months
Progression-free survival on/after study medication
The time from the date of the start of maintenance treatment to the date of documented progressive disease (PD) or death, whichever comes first.
Measured: From date of first treatment until date of first documented progression, date of further anti-myeloma therapy or date of death from any cause, whichever came first, assessed up to 96 months
Duration of response
The time from the date of the first IRC determined response to the date of first IRC PD or death, whichever occurs first. Duration of response will determined only for patients who have achieved CR, VGPR, or PR.
Measured: From date of first treatment until date of first documented progression, date of further anti-myeloma therapy or date of death from any cause, whichever came first, assessed up to 96 months
Overall survival
Defined as the time from the date of randomization to death from any cause
Measured: From date of first treatment until date of death from any cause, assessed up to 96 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Sep 2020
- Study start2 Jun 2021
- Primary completion31 Dec 2027 (estimated)
- Study completion31 Dec 2032 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Multiple MyelomaStudies of the same condition, open and under way.
- More trials run by Karolinska InstitutetThe 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
- Model description
- After confirmation of the eligibility criteria, patients will be randomly assigned in a 1:1 ratio to one of the two treatment arms: Isatuximab in combination with CellProtect (ISA/CellProtect experimental arm), or Isatuximab (ISA, control arm). Randomization will be at diagnosis and before the start of the treatment for patients eligible for SCT. Treatment administration will start within 100 days from AST date. Patients will be treated until disease progression (max 3 years), unacceptable adverse event (AE), patient's decision to stop the study treatment, death or any other reasons, whichever occurs first. Closing of randomization will occur after a total of approximately 60 patients have been randomized. After randomisation, patients in experimental arm will donate starting material for the production of the IMP. Manufacturing of CellProtect is promptly initiated for patients randomised to the active IMP arm A.
- Masking
- None (open label)
- Enrolment
- 62 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Karolinska Institutet
- Sponsor type
- University, hospital or other
- Collaborators
- Sanofi, XNK Therapeutics AB, Sweden
- Responsible party
- Principal investigator, Hareth Nahi, Karolinska Institutet
- Investigators
- Johan Lund, M.D., Principal investigator, Karolinska University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04558931
- Sponsor's protocol ID
- ISA-HC-NK
- Status last verified
- Oct 2023
- First submitted
- 11 Sep 2020
- Last updated
- 11 Oct 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open, Randomised, Controlled, Phase II Trial of CellProtect in Combination With Isatuximab Antibody Versus Isatuximab Antibody Alone as Maintenance Treatment in Patients With Multiple Myeloma Undergoing High Dose Treatment
- ClinicalTrials.gov ID
- NCT04558931
- Acronym / sponsor ID
- ISA-HC-NK
- Conditions
- Multiple Myeloma
- Keywords
- NK cells, Consolidation, Isatuximab, SAR650984
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 62 participants (estimated)
- Lead sponsor
- Karolinska InstitutetUniversity, hospital or other
- Collaborators
- Sanofi, XNK Therapeutics AB, Sweden
- Study start
- 2 Jun 2021 (actual)
- Primary completion
- 31 Dec 2027 (estimated)
- Study completion
- 31 Dec 2032 (estimated)
- First posted
- 22 Sep 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Prospective, single center, randomized, open label, parallel group, 2-arm study assessing the clinical benefit in term of enhancement of overall response rate of Isatuximab in combination with CellProtect as compared to Isatuximab for the treatment of patients with newly diagnosed multiple myeloma who are eligible for stem cell transplantation (SCT) as maintenance after SCT.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- After confirmation of the eligibility criteria, patients will be randomly assigned in a 1:1 ratio to one of the two treatment arms: Isatuximab in combination with CellProtect (ISA/CellProtect experimental arm), or Isatuximab (ISA, control arm). Randomization will be at diagnosis and before the start of the treatment for patients eligible for SCT. Treatment administration will start within 100 days from AST date. Patients will be treated until disease progression (max 3 years), unacceptable adverse event (AE), patient's decision to stop the study treatment, death or any other reasons, whichever occurs first. Closing of randomization will occur after a total of approximately 60 patients have been randomized. After randomisation, patients in experimental arm will donate starting material for the production of the IMP. Manufacturing of CellProtect is promptly initiated for patients randomised to the active IMP arm A.
| Arm | Type | Receives |
|---|---|---|
| A - Isatuximab/CellProtect | Experimental | Drug: CellProtect, Drug: IsatuximabIsatuximab will be given intravenously (IV) at the dose of 10 mg/kg on Days 1, 8, 15, 22 (cycle 1), 36, 50 (cycle 2), 64, 78 (cycle 3) and monthly thereafter (cycles 4-36). CellProtect will be given IV infusion at the dose of 3x10^7 cells/kg day 29 , 43 and 3-10x10^7 on day 57. Each cycle will be 28 days, after completion of third cycles, patients will continue with Isatuximab alone until disease progression, unacceptable AE, death, completion of 3 years of treatment or patient's decision to discontinue, whichever occurs first. |
| B - Isatuximab | Active comparator | Drug: IsatuximabIsatuximab will be given intravenously (IV) at the dose of 10 mg/kg on Days 1, 8, 15, 22 (cycle 1), 36, 50 (cycle 2), 64, 78 (cycle 3) and monthly thereafter (cycles 4-36). Each cycle will be 28 days, after completion of third cycles, patients will continue with Isatuximab alone until disease progression, unacceptable AE, death, completion of 3 years of treatment or patient's decision to discontinue, whichever occurs first. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- I1. Active multiple myeloma, as defined by the IMWG criteria.
- I3. Serum monoclonal (M)-protein ≥1.0 g/dL measured using serum protein immunoelectrophoresis a.and/or I4. Urine M-protein ≥200 mg/24 hours measured using urine protein immunoelectrophoresis
- and/or I5. in patients without measurable M protein in serum or urine as per previous criteria, serum immunoglobulin free light chain (sFLC) ≥10 mg/dL and abnormal serum immunoglobulin kappa lambda free light chain ratio <0.26 or >1.65.
- I6. Patients who are newly diagnosed and considered for high-dose chemotherapy I7. Patient has given voluntary written informed consent before performance of any study related procedures not part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to his/her medical care.
- I8. ≥18 years of age (and satisfying the legal age of consent in the jurisdiction in which the study is taking place) I9. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1 I10. Male or Female
Key exclusion criteria (13 listed)
- E1. Prior or concurrent exposure to NK cells and NK like T cells, or Approved or investigational treatments for MM.
- E2. Received any investigational drug within 14 days or 5 half-lives of the investigational drug, whichever is longer.
- E3. Diagnosis of primary amyloidosis, monoclonal gammopathy of undetermined significance, or smoldering multiple myeloma (asymptomatic multiple myeloma with absence of related organ or tissue impairment end organ damage).
- E4. Diagnosis of Waldenström's disease, or other conditions in which IgM M-protein is present in the absence of a clonal plasma cell infiltration with lytic bone lesions.
- E5. Prior or current systemic therapy, or SCT for symptomatic multiple myeloma, with the exception of an emergency use of a short course (equivalent of dexamethasone 40 mg/day for 4 days) of corticosteroids, if completed within 14 days prior to randomization.
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 |
|---|---|---|
| CellProtectAlso: Autologous NK cellIn vitro expanded and activated autologous NK cells | Drug | A - Isatuximab/CellProtect |
| IsatuximabAlso: SarclisaNaked immunoglobulin (Ig) G1 monoclonal antibody (mAb) that selectively binds to the human cell surface antigen molecule classified as cluster of differentiation (CD) 38 | Drug | A - Isatuximab/CellProtect, B - Isatuximab |
Primary outcome
Overall response rate as the occurrence of very good partial response or better after maintenance start
Time frame: From date of first treatment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 96 months
Evaluate in both arms the occurance after maintenance start of: Very good partial response (VGPR) or better rate, as defined by the International Myeloma Working Group (IMWG) criteria.
Change in minimal residual disease (MRD) negativity rate
Time frame: Before start of maintenance, after first Isatuximab cycle, before start of 4th Isatuximab cycle and at 12 and 24 months after start of maintenance
Assessment of changes in MRD negativity rate in patients with complete and very good partial response as well as conversion of MRD positivity to MRD negativity.
5 secondary outcomes
adverse events
Time frame: From first dose of study treatment up to 30 days after the last dose of study treatment or initiation of further anti-myeloma therapy, whichever occurs first, assessed up to 96 months
Time to progression
Time frame: From date of first treatment until date of first documented progression, date of further anti-myeloma therapy or date of death from any cause, whichever came first, assessed up to 96 months
Progression-free survival on/after study medication
Time frame: From date of first treatment until date of first documented progression, date of further anti-myeloma therapy or date of death from any cause, whichever came first, assessed up to 96 months
Duration of response
Time frame: From date of first treatment until date of first documented progression, date of further anti-myeloma therapy or date of death from any cause, whichever came first, assessed up to 96 months
Overall survival
Time frame: From date of first treatment until date of death from any cause, assessed up to 96 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Oct 2023.
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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.
Johan Lund, M.D. principal investigator
Karolinska University Hospital
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 CellProtect and Isatuximab in people with Multiple Myeloma, run by Karolinska Institutet at 1 site in Sweden.
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 13 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: looking for participants now, as of the sponsor's last update on 11 Oct 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 Sweden. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Johan Lund, M.D. (+46(0)8 58 58 00 00, johan.l.lund@regionstockholm.se), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall response rate as the occurrence of very good partial response or better after maintenance start (time frame: From date of first treatment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 96 months). The study lists 2 primary outcomes in all. 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 11 Oct 2023.