Back to resultsEfficacy of the antiCD38 Monoclonal Antibody Isatuximab in the Treatment of PCRA by Major ABO Mismatch After Allogeneic Hematopoietic Stem Cell Transplantation (ErythroSIM)
Primary Purpose
Immunological Pure Red Cell Aplasia
Status
Not yet recruiting
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Isatuximab
Sponsored by
About this trial
This is an interventional treatment trial for Immunological Pure Red Cell Aplasia
Eligibility Criteria
Inclusion Criteria:
- 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)
Exclusion Criteria:
- 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
- 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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
No Intervention
Arm Label
Isatuximab arm
comparator arm
Arm Description
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.
No treatment, supportive care will be allowed.
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
Number of red blood cell transfusions after randomization
Ferritin levels
Ferritin levels
Ferritin levels
Adverse events (CTC-AE grade ≥ 2)
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.
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.
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.
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.
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.
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.
Spontaneous resolution of PRCA between day 60 and 6 months post-transplant
Antibody level (anti A and/or anti B titers)
Antibody level (anti A and/or anti B titers)
Antibody level (anti A and/or anti B titers)
Antibody level (anti A and/or anti B titers)
Antibody level (anti A and/or anti B titers)
Antibody level (anti A and/or anti B titers)
Antibody level (anti A and/or anti B titers)
Antibody level (anti A and/or anti B titers)
Number of days of hospitalization
Number of days of transfusions support
Number of days of chelation treatments
Full Information
NCT ID
NCT05559827
First Posted
September 14, 2022
Last Updated
September 26, 2022
Sponsor
Assistance Publique - Hôpitaux de Paris
1. Study Identification
Unique Protocol Identification Number
NCT05559827
Brief Title
Efficacy of the antiCD38 Monoclonal Antibody Isatuximab in the Treatment of PCRA by Major ABO Mismatch After Allogeneic Hematopoietic Stem Cell Transplantation
Acronym
ErythroSIM
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
Study Type
Interventional
2. Study Status
Record Verification Date
September 2022
Overall Recruitment Status
Not yet recruiting
Study Start Date
September 2022 (Anticipated)
Primary Completion Date
October 2026 (Anticipated)
Study Completion Date
October 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Assistance Publique - Hôpitaux de Paris
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief 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. 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)
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Immunological Pure Red Cell Aplasia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
90 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Isatuximab arm
Arm Type
Experimental
Arm Description
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.
Arm Title
comparator arm
Arm Type
No Intervention
Arm Description
No treatment, supportive care will be allowed.
Intervention Type
Drug
Intervention Name(s)
Isatuximab
Intervention Description
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.
Primary Outcome Measure Information:
Title
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
Secondary Outcome Measure Information:
Title
Number of red blood cell transfusions after randomization
Time Frame
from randomization through study completion, an average of 9 months after randomization
Title
Ferritin levels
Time Frame
at month 6 post-transplant
Title
Ferritin levels
Time Frame
at month 9 post-transplant
Title
Ferritin levels
Time Frame
at month 15 post-transplant
Title
Adverse events (CTC-AE grade ≥ 2)
Time Frame
up to 13 months post transplant
Title
Quality of life questionnaire (EORTC QLQ-C30- v3)
Description
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.
Time Frame
at day 60
Title
Quality of life questionnaire (EORTC QLQ-C30- v3)
Description
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.
Time Frame
at day 100
Title
Quality of life questionnaire (EORTC QLQ-C30- v3)
Description
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.
Time Frame
at 6 months
Title
Quality of life questionnaire (EORTC QLQ-C30- v3)
Description
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.
Time Frame
at 9 months
Title
Quality of life questionnaire (EORTC QLQ-C30- v3)
Description
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.
Time Frame
at 12 months
Title
Quality of life questionnaire (EORTC QLQ-C30- v3)
Description
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.
Time Frame
at 15 months post-transplant
Title
Spontaneous resolution of PRCA between day 60 and 6 months post-transplant
Time Frame
at 6 months post-transplant
Title
Antibody level (anti A and/or anti B titers)
Time Frame
at day 60 post transplant
Title
Antibody level (anti A and/or anti B titers)
Time Frame
at day 100 post transplant
Title
Antibody level (anti A and/or anti B titers)
Time Frame
at day 15 post randomization
Title
Antibody level (anti A and/or anti B titers)
Time Frame
at day 29 post randomization
Title
Antibody level (anti A and/or anti B titers)
Time Frame
at day 45 post randomization
Title
Antibody level (anti A and/or anti B titers)
Time Frame
at month 3 post randomization
Title
Antibody level (anti A and/or anti B titers)
Time Frame
at month 6 post-randomization
Title
Antibody level (anti A and/or anti B titers)
Time Frame
at month 9 post-randomization
Title
Number of days of hospitalization
Time Frame
up to 9 months post ranomization
Title
Number of days of transfusions support
Time Frame
up to 9 months post randomization
Title
Number of days of chelation treatments
Time Frame
up to 9 months post randomization
10. Eligibility
Sex
All
Minimum Age & Unit of Time
15 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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)
Exclusion Criteria:
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
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Aliénor XHAARD
Phone
+33142385073
Email
alienor.xhaard@aphp.fr
First Name & Middle Initial & Last Name or Official Title & Degree
Matthieu Resche-Rigon
Phone
+33142499742
Email
matthieu.resche-rigon@u-paris.fr
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Learn more about this trial
Efficacy of the antiCD38 Monoclonal Antibody Isatuximab in the Treatment of PCRA by Major ABO Mismatch After Allogeneic Hematopoietic Stem Cell Transplantation
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