RECRUITING

Open-Label, Phase II Trial of Isatuximab for Patients With Refractory Immune Cytopenias After Allogeneic Hematopoietic Cell Transplantation

Conditions

Blood Cancer Refractory Immune Cytopenias Isatuximab Allogeneic Hematopoietic Cell Transplantation 23-119 Memorial Sloan Kettering

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

The purpose of this study is to find out whether isatuximab is an effective treatment for people who developed immune cytopenias/ICs after allogeneic hematopoietic cell transplant/allo-HCT.

Official Title

Open-Label, Phase II Trial of Isatuximab for Patients With Refractory Immune Cytopenias After Allogeneic Hematopoietic Cell Transplantation

Quick Facts

Study Start:2023-07-21

Study Completion:2026-06-29

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05873205

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* Age ≥ 18 years (There are no dosing/AE data for isatuximab in children). * Disease for which patient underwent an allo-HCT is in documented remission. * Patients must have previously had documented primary neutrophil and platelet engraftment, defined as: * Neutrophil engraftment: the first of 3 successive days with an absolute neutrophil count of ≥500/μL after post-transplantation nadir. * Platelet engraftment: the first of 3 consecutive days with a platelet count of 20,000/μL or higher in the absence of platelet transfusion for 7 consecutive days. * Patients must be at least 45 days post allogeneic HCT to enroll. * Patients must be diagnosed with IC(s) based on the following criteria: * DAT negative AIHA may be included providing exclusion of alternative etiology of hemolytic anemia. * For ITP: decreasing thrombocytopenia from baseline (i.e., from the patients typical platelet count prior to ITP) and platelet count ≤30 K/µL or requiring platelet transfusions in the absence of other causes of thrombocytopenia (including drug-induced thrombocytopenia), and with normal or increased bone marrow megakaryocytes. * For PRCA: severe anemia (hemoglobin \<8 g/dL without transfusions) with reticulocytopenia (reticulocyte percentage \<1% and/or absolute reticulocyte count \<10,000/µL) after exclusion of obvious causes of anemia. * Patients with concomitant ICs can be enrolled on the study. * Patient must have responded incompletely to their previous treatment, defined as: * Corticosteroid refractoriness: defined as a clear progression or minimal responsiveness of IC(s) after ≥7 days of treatment with prednisone equivalent of ≥1 mg/kg/day. * Corticosteroid dependence: defined as dependence on prednisone equivalent of ≥0.5 mg/kg/day to maintain hemoglobin level ≥2 g/dL nadir level (for AIHA and/or PRCA), and/or platelet count ≥30 x 109/L or ≥2-fold increase from nadir level (for ITP). * Refractory IC(s) after ≥2 treatment lines including corticosteroids (≥0.5 mg/kg/day prednisone equivalent), IVIG (400 mg/kg/day for 2 to 5 days), and/or rituximab, etc. * For rituximab treated patients, refractoriness will be defined as no or minimal response within 2 weeks of completing ≥4 doses of rituximab. * Absolute neutrophil count (ANC) ≥ 1.0 x 109/L. * No active hepatitis viral infection or on active treatment for hepatitis infection. * Female patients of childbearing potential are eligible if the patient has had a negative serum or urine pregnancy test within 10-14 days prior to starting isatuximab therapy. * Male patients must agree to not donate sperm while on the study and for at least 5 months after the last dose of study drug. They must agree to use contraception during the intervention period and for at least 5 months after the last dose of isatuximab treatment. * Subjects must be able to give informed consent.	* Presence of relapse/progression of malignant disease for which the patient underwent allo-HCT * Patients with anemia and/or thrombocytopenia related to transplant-associated thrombotic microangiopathy. * Patients with active GVHD requiring therapy may be eligible if the GVHD is responsive to treatment (\< grade 4 in severity), and after agreement between the sponsor and principal investigator. * Organ insufficiency based on above criteria. * Pregnancy or unwillingness to agree to birth control as noted above. * Known to be HIV+ or to have active hepatitis A, B, or C infection (i.e., with viremia). * Patients can be eligible if anti-HBc seropositive (with or without positive anti-HBs), but HBsAg and HBV DNA are negative. * Patients with antiviral therapy for HCV started before initiation of treatment and positive Hep C antibodies are eligible. The antiviral therapy for Hep C should continue throughout the treatment period until seroconversion. Patients with positive anti-Hep C and undetectable Hep C RNA without antitviral therapy for Hep C are eligible. * Any clinically significant, uncontrolled medical condition(s), including infection(s) that, in the Investigator's opinion, would expose the patient to excessive risk or may interfere with compliance or interpretation of the study results. * Hypersensitivity or history of intolerance to steroids, mannitol, pregelatinized starch, sodium stearyl fumarate, histidine (as base and hydrochloride salt), arginine hydrochloride, poloxamer 188, sucrose, prior anti-CD38 moAb such as daratumumab, or any of the other components of study intervention that are not amenable to premedication with steroids and H2 blockers or would prohibit further treatment with these agents. * Received any investigational drug within 14 days or 5 half-lives of the investigational drug prior to initiation of study intervention, whichever is longer. In case of very aggressive disease (e.g., acute leukemia) delay could be shortened after agreement between sponsor and principal investigator, in absence of residual toxicities from previous therapy. * Patients on post-HCT maintenance therapy to reduce the risk of relapse (for patients with hematologic malignancies) or GVHD (e.g., FLT3 inhibitors, etc.) may be eligible after agreement between the sponsor and principal investigator. * Contraindication to any concomitant medication, including pre-medications or hydration given prior to therapy * Participants who are unable to consent to the study or comply with the study procedures.

Inclusion Criteria

Exclusion Criteria

* Age ≥ 18 years (There are no dosing/AE data for isatuximab in children).
* Disease for which patient underwent an allo-HCT is in documented remission.
* Patients must have previously had documented primary neutrophil and platelet engraftment, defined as:
* Neutrophil engraftment: the first of 3 successive days with an absolute neutrophil count of ≥500/μL after post-transplantation nadir.
* Platelet engraftment: the first of 3 consecutive days with a platelet count of 20,000/μL or higher in the absence of platelet transfusion for 7 consecutive days.
* Patients must be at least 45 days post allogeneic HCT to enroll.
* Patients must be diagnosed with IC(s) based on the following criteria:
* DAT negative AIHA may be included providing exclusion of alternative etiology of hemolytic anemia.
* For ITP: decreasing thrombocytopenia from baseline (i.e., from the patients typical platelet count prior to ITP) and platelet count ≤30 K/µL or requiring platelet transfusions in the absence of other causes of thrombocytopenia (including drug-induced thrombocytopenia), and with normal or increased bone marrow megakaryocytes.
* For PRCA: severe anemia (hemoglobin \<8 g/dL without transfusions) with reticulocytopenia (reticulocyte percentage \<1% and/or absolute reticulocyte count \<10,000/µL) after exclusion of obvious causes of anemia.
* Patients with concomitant ICs can be enrolled on the study.
* Patient must have responded incompletely to their previous treatment, defined as:
* Corticosteroid refractoriness: defined as a clear progression or minimal responsiveness of IC(s) after ≥7 days of treatment with prednisone equivalent of ≥1 mg/kg/day.
* Corticosteroid dependence: defined as dependence on prednisone equivalent of ≥0.5 mg/kg/day to maintain hemoglobin level ≥2 g/dL nadir level (for AIHA and/or PRCA), and/or platelet count ≥30 x 109/L or ≥2-fold increase from nadir level (for ITP).
* Refractory IC(s) after ≥2 treatment lines including corticosteroids (≥0.5 mg/kg/day prednisone equivalent), IVIG (400 mg/kg/day for 2 to 5 days), and/or rituximab, etc.
* For rituximab treated patients, refractoriness will be defined as no or minimal response within 2 weeks of completing ≥4 doses of rituximab.
* Absolute neutrophil count (ANC) ≥ 1.0 x 109/L.
* No active hepatitis viral infection or on active treatment for hepatitis infection.
* Female patients of childbearing potential are eligible if the patient has had a negative serum or urine pregnancy test within 10-14 days prior to starting isatuximab therapy.
* Male patients must agree to not donate sperm while on the study and for at least 5 months after the last dose of study drug. They must agree to use contraception during the intervention period and for at least 5 months after the last dose of isatuximab treatment.
* Subjects must be able to give informed consent.

* Presence of relapse/progression of malignant disease for which the patient underwent allo-HCT
* Patients with anemia and/or thrombocytopenia related to transplant-associated thrombotic microangiopathy.
* Patients with active GVHD requiring therapy may be eligible if the GVHD is responsive to treatment (\< grade 4 in severity), and after agreement between the sponsor and principal investigator.
* Organ insufficiency based on above criteria.
* Pregnancy or unwillingness to agree to birth control as noted above.
* Known to be HIV+ or to have active hepatitis A, B, or C infection (i.e., with viremia).
* Patients can be eligible if anti-HBc seropositive (with or without positive anti-HBs), but HBsAg and HBV DNA are negative.
* Patients with antiviral therapy for HCV started before initiation of treatment and positive Hep C antibodies are eligible. The antiviral therapy for Hep C should continue throughout the treatment period until seroconversion. Patients with positive anti-Hep C and undetectable Hep C RNA without antitviral therapy for Hep C are eligible.
* Any clinically significant, uncontrolled medical condition(s), including infection(s) that, in the Investigator's opinion, would expose the patient to excessive risk or may interfere with compliance or interpretation of the study results.
* Hypersensitivity or history of intolerance to steroids, mannitol, pregelatinized starch, sodium stearyl fumarate, histidine (as base and hydrochloride salt), arginine hydrochloride, poloxamer 188, sucrose, prior anti-CD38 moAb such as daratumumab, or any of the other components of study intervention that are not amenable to premedication with steroids and H2 blockers or would prohibit further treatment with these agents.
* Received any investigational drug within 14 days or 5 half-lives of the investigational drug prior to initiation of study intervention, whichever is longer. In case of very aggressive disease (e.g., acute leukemia) delay could be shortened after agreement between sponsor and principal investigator, in absence of residual toxicities from previous therapy.
* Patients on post-HCT maintenance therapy to reduce the risk of relapse (for patients with hematologic malignancies) or GVHD (e.g., FLT3 inhibitors, etc.) may be eligible after agreement between the sponsor and principal investigator.
* Contraindication to any concomitant medication, including pre-medications or hydration given prior to therapy
* Participants who are unable to consent to the study or comply with the study procedures.

Contacts and Locations

Study Contact

Michael Scordo, MD

CONTACT

646-608-3771

scordom@mskcc.org

Sergio Geralt, MD

CONTACT

646-608-3731

GiraltS@mskcc.org

Principal Investigator

Michael Scorder, MD

PRINCIPAL_INVESTIGATOR

Memorial Sloan Kettering Cancer Center

Study Locations (Sites)

Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)

Basking Ridge, New Jersey, 07920

United States

Memorial Sloan Kettering Monmouth (Limited Protocol Activities)

Middletown, New Jersey, 07748

United States

Memorial Sloan Kettering Bergen (Limited protocol activities)

Montvale, New Jersey, 07645

United States

Memorial Sloan Kettering Suffolk-Commack (All Protocol Activities )

Commack, New York, 11725

United States

Memorial Sloan Kettering Westchester (Limited Protocol Activities)

Harrison, New York, 10604

United States

Memorial Sloan Kettering Cancer Center (All Protocol Activities)

New York, New York, 10065

United States

Memorial Sloan Kettering Nassau (All protocol activities)

Rockville Centre, New York, 11553

United States

Collaborators and Investigators

Sponsor: Memorial Sloan Kettering Cancer Center

Michael Scorder, MD, PRINCIPAL_INVESTIGATOR, Memorial Sloan Kettering Cancer Center

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2023-07-21

Study Completion Date2026-06-29

Study Record Updates

Study Start Date2023-07-21

Study Completion Date2026-06-29

Terms related to this study

Keywords Provided by Researchers

Refractory Immune Cytopenias
Blood Cancer
Isatuximab
Allogeneic Hematopoietic Cell Transplantation
23-119
Memorial Sloan Kettering

Additional Relevant MeSH Terms

Blood Cancer
Refractory Immune Cytopenias