Immunological Pure Red Cell AplasiaPhase 2ErythroSIMNCT05559827
Efficacy of the antiCD38 Monoclonal Antibody Isatuximab in the Treatment of PCRA by Major ABO Mismatch After Allogeneic Hematopoietic Stem Cell Transplantation
A Phase 2 study testing Isatuximab in people with Immunological Pure Red Cell Aplasia, run by Assistance Publique - Hôpitaux de Paris.
Trial summary
A quarter of allogeneic hematopoietic stem cell transplantation are performed in a situation of major ABO mismatch exposing patients to the risk of immunological pure red cell aplasia (PRCA) after transplant. Read more about this study
- Who is it for?
- Ages 15 years and older
- Conditions the study is for
- Immunological Pure Red Cell Aplasia
- What is being tested?
- Isatuximab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 90 participants
- Where
- No sites listed yet
- Study dates
- Sep 2022to Oct 2026
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 15 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Aged 15 years or older
- Having receiving an allogeneic hematopoietic stem cell transplantation in condition of major ABO mismatch
- PCRA defined by persistent red blood cell transfusion dependence at day 60 post-transplant with reticulocytes count under 10 G/L despite full donor chimerism and a good leucocytes (>1 G/L) and platelet (>50G/L) recovery
- No relapse or progression of underlying disease
- Contraception methods must be prescribed during all the duration of the research and using effective contraceptive methods during treatment for women of childbearing age (continue abstinence from heterosexual intercourse is accepted) and for man during the study treatment period and for at least 5 months after the last dose of study treatment and refrain from donating sperm during this period
- With health insurance coverage
- Having signed a written informed consent (2 parents for patients aged less than 18)
Who cannot join
- Aged < 15 years
- Relapse of underlying disease
- Leucocyte chimerism < 95%
- PRCA related to Parvovirus B19 infection (positive blood PCR)
- Known to be HIV+ or to have hepatitis A, B, or C active infection
- Active tuberculosis
Show all 17Show fewer
- Pregnancy (βHCG positive) or breast-feeding.
- Patient receiving recombinant human erythropoietin.
- Patient receiving proteasome inhibitor (Bortezomib for example).
- Patient receiving thrombopoietin receptor agonists (ARTPO).
- Patient receiving plasma or plasmapheresis exchanges after transplant.
- Planned to receive any investigational drug within 14 days or 5 half-lives of the investigational drug, whichever is longer.
- Any clinically significant, uncontrolled medical conditions that, in the Investigator's opinion, would expose excessive risk to the patient or may interfere with compliance or interpretation of the study results.
- Hypersensitivity to the active substance or history of intolerance to steroids, mannitol, pregelatinized starch, sodium stearyl fumarate, histidine (as base and hydrochloride salt), 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.
- Who have any debilitating medical or psychiatric illness
- Under tutorship or curatorship
- Who not understand informed consent for an optimal treatment and follow-up
Trial locations and contacts
No sites are listed yet.
About this study
Official title: Randomized Prospective Trial Evaluating the Efficacy of the antiCD38 Monoclonal Antibody Isatuximab in the Treatment of PCRA by Major ABO Mismatch After Allogeneic Hematopoietic Stem Cell Transplantation
A quarter of allogeneic hematopoietic stem cell transplantation are performed in a situation of major ABO mismatch exposing patients to the risk of immunological pure red cell aplasia (PRCA) after transplant. PCRA after transplant is defined as anemia with low reticulocytes count (under 10 G/L) after day 60 despite good leucocytes and platelet engraftment, full donor chimerism, associated with the persistence of recipients hemagglutinins (anti-A or anti-B antibodies). Bone marrow evaluation when performed show erythroid hypoplasia. Red blood cells transfusions are necessary every two weeks until remission leading to impaired quality of life (anemia, repeated hospitalization), iron overload, and need for iron chelation therapy. Treatments currently used are inefficient (anti CD20 monoclonal antibodies, EPO, steroids, plasma exchanges, proteasome inhibitors) or at risk of severe acute GVHD (donor lymphocytes infusion). PRCA has been demonstrated to be associated with the persistence of recipient's plasma cells.
Anti-CD38 monoclonal antibodies which targets plasma cells secreting hemagglutinins responsible of PCRA are a promising treatment: 6 cases reported in the literature support a rapid and sustain efficacy but a prospective randomized evaluation of its efficacy and safety in this context is necessary.
The main objective of the study is to assess the efficacy of the treatment of PRCA by isatuximab after allogeneic hematopoietic stem cell transplant compared to supportive care only control group (reduction in PRCA resolution time in days)
- Conditions
- Immunological Pure Red Cell Aplasia
- Being tested
- Isatuximab
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IsatuximabDrug
Isatuximab treatment at a dose of 10 mg/kg by intravenous route. The first injection of isatuximab will be performed at randomization (month 6 +/- 2 days). A second injection may be performed at day 15 if the reticulocytes <10 G / L, and a third at day 29 if reticulocytes <10 G / L. Patients will be assessed on day 1, day 15, day 29, day 45, 2 months, 3 months, 6 months and 9 months after randomization.
| Study group | Role | What they receive |
|---|---|---|
| Isatuximab arm | Experimental | Isatuximab treatment at a dose of 10 mg/kg by intravenous route. The first injection of isatuximab will be performed at randomization (month 6 +/- 2 days). A second injection may be performed at day 15 if the reticulocytes <10 G / L, and a third at day 29 if reticulocytes <10 G / L. Patients will be assessed on day 1, day 15, day 29, day 45, 2 months, 3 months, 6 months and 9 months after randomization. Receives: Drug: Isatuximab |
| comparator arm | No intervention | No treatment, supportive care will be allowed. |
What is being measured
The primary outcome is the main question the study is designed to answer.
time interval between randomization (corresponding to the M6 post-transplant) and resolution of PRCA (date of resolution of reticulocytopenia) treated or not by the anti-CD 38 monoclonal antibody isatuximab
Measured: 9 months post randomization
Secondary outcomes (23)
Number of red blood cell transfusions after randomization
Measured: from randomization through study completion, an average of 9 months after randomization
Ferritin levels
Measured: at month 6 post-transplant
Ferritin levels
Measured: at month 9 post-transplant
Ferritin levels
Measured: at month 15 post-transplant
Adverse events (CTC-AE grade ≥ 2)
Measured: up to 13 months post transplant
Quality of life questionnaire (EORTC QLQ-C30- v3)
Quality of life evaluated using questionnaire "European Organization for Research and Treatment of Cancer Quality of Life Questionnaire" (EORTC QLQ-C30- v3). The QLQ-C30 is composed of both multi-item scales and single-item measures. These include five functional scales, three symptom scales, a global health status / QoL scale, and six single items. Each of the multi-item scales includes a different set of items - no item occurs in more than one scale. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level. A high score for a functional scale represents a high/healthy level of functioning. A high score for the global health status/ QoL represents a high QoL and a high score for a symptom scale/item represents a high level of symptomatology/problems.
Measured: at day 60
Quality of life questionnaire (EORTC QLQ-C30- v3)
Quality of life evaluated using questionnaire "European Organization for Research and Treatment of Cancer Quality of Life Questionnaire" (EORTC QLQ-C30- v3). The QLQ-C30 is composed of both multi-item scales and single-item measures. These include five functional scales, three symptom scales, a global health status / QoL scale, and six single items. Each of the multi-item scales includes a different set of items - no item occurs in more than one scale. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level. A high score for a functional scale represents a high/healthy level of functioning. A high score for the global health status/ QoL represents a high QoL and a high score for a symptom scale/item represents a high level of symptomatology/problems.
Measured: at day 100
Quality of life questionnaire (EORTC QLQ-C30- v3)
Quality of life evaluated using questionnaire "European Organization for Research and Treatment of Cancer Quality of Life Questionnaire" (EORTC QLQ-C30- v3). The QLQ-C30 is composed of both multi-item scales and single-item measures. These include five functional scales, three symptom scales, a global health status / QoL scale, and six single items. Each of the multi-item scales includes a different set of items - no item occurs in more than one scale. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level. A high score for a functional scale represents a high/healthy level of functioning. A high score for the global health status/ QoL represents a high QoL and a high score for a symptom scale/item represents a high level of symptomatology/problems.
Measured: at 6 months
Quality of life questionnaire (EORTC QLQ-C30- v3)
Quality of life evaluated using questionnaire "European Organization for Research and Treatment of Cancer Quality of Life Questionnaire" (EORTC QLQ-C30- v3). The QLQ-C30 is composed of both multi-item scales and single-item measures. These include five functional scales, three symptom scales, a global health status / QoL scale, and six single items. Each of the multi-item scales includes a different set of items - no item occurs in more than one scale. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level. A high score for a functional scale represents a high/healthy level of functioning. A high score for the global health status/ QoL represents a high QoL and a high score for a symptom scale/item represents a high level of symptomatology/problems.
Measured: at 9 months
Quality of life questionnaire (EORTC QLQ-C30- v3)
Quality of life evaluated using questionnaire "European Organization for Research and Treatment of Cancer Quality of Life Questionnaire" (EORTC QLQ-C30- v3). The QLQ-C30 is composed of both multi-item scales and single-item measures. These include five functional scales, three symptom scales, a global health status / QoL scale, and six single items. Each of the multi-item scales includes a different set of items - no item occurs in more than one scale. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level. A high score for a functional scale represents a high/healthy level of functioning. A high score for the global health status/ QoL represents a high QoL and a high score for a symptom scale/item represents a high level of symptomatology/problems.
Measured: at 12 months
Quality of life questionnaire (EORTC QLQ-C30- v3)
Quality of life evaluated using questionnaire "European Organization for Research and Treatment of Cancer Quality of Life Questionnaire" (EORTC QLQ-C30- v3). The QLQ-C30 is composed of both multi-item scales and single-item measures. These include five functional scales, three symptom scales, a global health status / QoL scale, and six single items. Each of the multi-item scales includes a different set of items - no item occurs in more than one scale. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level. A high score for a functional scale represents a high/healthy level of functioning. A high score for the global health status/ QoL represents a high QoL and a high score for a symptom scale/item represents a high level of symptomatology/problems.
Measured: at 15 months post-transplant
Spontaneous resolution of PRCA between day 60 and 6 months post-transplant
Measured: at 6 months post-transplant
Antibody level (anti A and/or anti B titers)
Measured: at day 60 post transplant
Antibody level (anti A and/or anti B titers)
Measured: at day 100 post transplant
Antibody level (anti A and/or anti B titers)
Measured: at day 15 post randomization
Antibody level (anti A and/or anti B titers)
Measured: at day 29 post randomization
Antibody level (anti A and/or anti B titers)
Measured: at day 45 post randomization
Antibody level (anti A and/or anti B titers)
Measured: at month 3 post randomization
Antibody level (anti A and/or anti B titers)
Measured: at month 6 post-randomization
Antibody level (anti A and/or anti B titers)
Measured: at month 9 post-randomization
Number of days of hospitalization
Measured: up to 9 months post ranomization
Number of days of transfusions support
Measured: up to 9 months post randomization
Number of days of chelation treatments
Measured: up to 9 months post randomization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Sep 2022
- Study startSep 2022 (estimated)
- Primary completionOct 2026 (estimated)
- Study completionOct 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Immunological Pure Red Cell AplasiaStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe 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
- 90 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05559827
- Sponsor's protocol ID
- APHP200067
- Acronym
- ErythroSIM
- Status last verified
- Sep 2022
- First submitted
- 14 Sep 2022
- Last updated
- 29 Sep 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 29 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Prospective Trial Evaluating the Efficacy of the antiCD38 Monoclonal Antibody Isatuximab in the Treatment of PCRA by Major ABO Mismatch After Allogeneic Hematopoietic Stem Cell Transplantation
- ClinicalTrials.gov ID
- NCT05559827
- Acronym / sponsor ID
- ErythroSIM / APHP200067
- Conditions
- Immunological Pure Red Cell Aplasia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 90 participants (estimated)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- Sep 2022 (estimated)
- Primary completion
- Oct 2026 (estimated)
- Study completion
- Oct 2026 (estimated)
- First posted
- 29 Sep 2022 (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.
A quarter of allogeneic hematopoietic stem cell transplantation are performed in a situation of major ABO mismatch exposing patients to the risk of immunological pure red cell aplasia (PRCA) after transplant. PCRA after transplant is defined as anemia with low reticulocytes count (under 10 G/L) after day 60 despite good leucocytes and platelet engraftment, full donor chimerism, associated with the persistence of recipients hemagglutinins (anti-A or anti-B antibodies). Bone marrow evaluation when performed show erythroid hypoplasia. Red blood cells transfusions are necessary every two weeks until remission leading to impaired quality of life (anemia, repeated hospitalization), iron overload, and need for iron chelation therapy. Treatments currently used are inefficient (anti CD20 monoclonal antibodies, EPO, steroids, plasma exchanges, proteasome inhibitors) or at risk of severe acute GVHD (donor lymphocytes infusion). PRCA has been demonstrated to be associated with the persistence of recipient's plasma cells.
Anti-CD38 monoclonal antibodies which targets plasma cells secreting hemagglutinins responsible of PCRA are a promising treatment: 6 cases reported in the literature support a rapid and sustain efficacy but a prospective randomized evaluation of its efficacy and safety in this context is necessary.
The main objective of the study is to assess the efficacy of the treatment of PRCA by isatuximab after allogeneic hematopoietic stem cell transplant compared to supportive care only control group (reduction in PRCA resolution time in days)
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Isatuximab arm | Experimental | Drug: IsatuximabIsatuximab treatment at a dose of 10 mg/kg by intravenous route. The first injection of isatuximab will be performed at randomization (month 6 +/- 2 days). A second injection may be performed at day 15 if the reticulocytes <10 G / L, and a third at day 29 if reticulocytes <10 G / L. Patients will be assessed on day 1, day 15, day 29, day 45, 2 months, 3 months, 6 months and 9 months after randomization. |
| comparator arm | No intervention | –No treatment, supportive care will be allowed. |
Who may qualify
- Ages
- 15 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (7 listed)
- Aged 15 years or older
- Having receiving an allogeneic hematopoietic stem cell transplantation in condition of major ABO mismatch
- PCRA defined by persistent red blood cell transfusion dependence at day 60 post-transplant with reticulocytes count under 10 G/L despite full donor chimerism and a good leucocytes (>1 G/L) and platelet (>50G/L) recovery
- No relapse or progression of underlying disease
- Contraception methods must be prescribed during all the duration of the research and using effective contraceptive methods during treatment for women of childbearing age (continue abstinence from heterosexual intercourse is accepted) and for man during the study treatment period and for at least 5 months after the last dose of study treatment and refrain from donating sperm during this period
Key exclusion criteria (17 listed)
- Aged < 15 years
- Relapse of underlying disease
- Leucocyte chimerism < 95%
- PRCA related to Parvovirus B19 infection (positive blood PCR)
- Known to be HIV+ or to have hepatitis A, B, or C active infection
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 |
|---|---|---|
| IsatuximabIsatuximab treatment at a dose of 10 mg/kg by intravenous route. The first injection of isatuximab will be performed at randomization (month 6 +/- 2 days). A second injection may be performed at day 15 if the reticulocytes <10 G / L, and a third at day 29 if reticulocytes <10 G / L. Patients will be assessed on day 1, day 15, day 29, day 45, 2 months, 3 months, 6 months and 9 months after randomization. | Drug | Isatuximab arm |
Primary outcome
time interval between randomization (corresponding to the M6 post-transplant) and resolution of PRCA (date of resolution of reticulocytopenia) treated or not by the anti-CD 38 monoclonal antibody isatuximab
Time frame: 9 months post randomization
23 secondary outcomes
Number of red blood cell transfusions after randomization
Time frame: from randomization through study completion, an average of 9 months after randomization
Ferritin levels
Time frame: at month 6 post-transplant
Ferritin levels
Time frame: at month 9 post-transplant
Ferritin levels
Time frame: at month 15 post-transplant
Adverse events (CTC-AE grade ≥ 2)
Time frame: up to 13 months post transplant
Quality of life questionnaire (EORTC QLQ-C30- v3)
Time frame: at day 60
Quality of life questionnaire (EORTC QLQ-C30- v3)
Time frame: at day 100
Quality of life questionnaire (EORTC QLQ-C30- v3)
Time frame: at 6 months
Quality of life questionnaire (EORTC QLQ-C30- v3)
Time frame: at 9 months
Quality of life questionnaire (EORTC QLQ-C30- v3)
Time frame: at 12 months
Quality of life questionnaire (EORTC QLQ-C30- v3)
Time frame: at 15 months post-transplant
Spontaneous resolution of PRCA between day 60 and 6 months post-transplant
Time frame: at 6 months post-transplant
Antibody level (anti A and/or anti B titers)
Time frame: at day 60 post transplant
Antibody level (anti A and/or anti B titers)
Time frame: at day 100 post transplant
Antibody level (anti A and/or anti B titers)
Time frame: at day 15 post randomization
Antibody level (anti A and/or anti B titers)
Time frame: at day 29 post randomization
Antibody level (anti A and/or anti B titers)
Time frame: at day 45 post randomization
Antibody level (anti A and/or anti B titers)
Time frame: at month 3 post randomization
Antibody level (anti A and/or anti B titers)
Time frame: at month 6 post-randomization
Antibody level (anti A and/or anti B titers)
Time frame: at month 9 post-randomization
Number of days of hospitalization
Time frame: up to 9 months post ranomization
Number of days of transfusions support
Time frame: up to 9 months post randomization
Number of days of chelation treatments
Time frame: up to 9 months post randomization
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Sep 2022.
- Individual participant dataSharing planned: Undecided
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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.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Isatuximab in people with Immunological Pure Red Cell Aplasia, run by Assistance Publique - Hôpitaux de Paris.
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 7 inclusion and 17 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: status not confirmed, as of the sponsor's last update on 29 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.
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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Aliénor XHAARD (+33142385073, alienor.xhaard@aphp.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
time interval between randomization (corresponding to the M6 post-transplant) and resolution of PRCA (date of resolution of reticulocytopenia) treated or not by the anti-CD 38 monoclonal antibody isatuximab (time frame: 9 months post randomization). 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 29 Sep 2022.