Blood and Lymph Conditions

All Conditions

Neoplasms

Digestive System Diseases

Thrombocytopenia

Gastrointestinal Neoplasms

Digestive System Neoplasms

Blood Platelet Disorders

Hematologic Diseases

Cytopenia

Gastrointestinal Diseases

All Drugs and Chemicals

Maleic acid

Enzyme Inhibitors

30 participants will be randomized into a 1:1 fashion and will be stratified based on the number of cytotoxic agents in the patient's chemotherapy regimen. Participants will complete study procedures as outlined:

Lead-In Period (Day 1 - 15)

* Pre-determined dose of Avatrombopag 1x daily.
* Participants failing to achieve a platelet count ≥100,000/µL within 2 weeks will be considered a treatment failure (and will proceed to the end-of-study visit).

On-Cycle Period (Day 15 - up to Week 6)

• Pre-determined dose of Avatrombopag 1x daily.

Follow-up Period

* End of Treatment on-site visit.
* Follow-up visit 30-42 days after End of Treatment visit.

30 participants will be randomized into a 1:1 fashion and will be stratified based on the number of cytotoxic agents in the patient's chemotherapy regimen. Participants will complete study procedures as outlined:

Lead-In Period (Day 1 - 15)

* Pre-determined dose of matching placebo 1x daily.
* Participants failing to achieve a platelet count ≥100,000/µL within 2 weeks will be considered a treatment failure (and will proceed to the end-of-study visit).

On-Cycle Period (Day 15 - up to Week 6)

• Pre-determined dose of matching placebo 1x daily.

Follow-up Period

* End of Treatment on-site visit.
* Follow-up visit 30-42 days after End of Treatment visit.

Thrombopoietin receptor agonist, tablet taken orally.

Avatrombopag

Lactose monohydrate, tablet taken orally.

Matching Placebo

Hanny Al-Samkari, MD

Gerald Soff, MD

Stephen Lattanzi, M.D.

Gerald A Soff, MD

Kanika Nair, M.D.

Joseph Shatzel, M.D.

Sandhya Panch, M.D.

The purpose of this study is to compare the efficacy of two study drugs, Avatrobopag versus placebo, to treat persistent Chemotherapy-Induced Thrombocytopenia (CIT) in patients with gastrointestinal (GI) malignancies receiving cytotoxic chemotherapy.

The names of the study drugs involved in this study are:

* Avatrombopag (a thrombopoietin receptor agonist)
* Matching placebo

This is a randomized, double-blinded, placebo-controlled, multicenter phase 2 clinical trial evaluating Avatrombopag versus placebo for Chemotherapy-Induced Thrombocytopenia (CIT) in patients with gastrointestinal (GI) malignancies. Avatrombopag may increase or stimulate megakaryocytes, which aid in producing blood platelets, resulting in an increased production of platelets.

* Participants will be "randomized" into one of the study groups: Group A: Avatrombopag or Group B: Matching placebo. Randomization means that a participant is put into a group by chance.
* All patients who complete the study (whether they received avatrombopag or placebo) have the opportunity to receive avatrombopag to treat CIT through a special free drug program available only to the participants of this study.

The U.S. Food and Drug Administration (FDA) has not approved avatrombopag for CIT, but it has been approved for other uses.

Study procedures include screening for eligibility, treatment visits, and blood tests.

Participants will receive the study treatment or placebo for up to seven weeks and will be followed for up to 42 days after the last dose.

It is expected that about 60 people will take part in this research study.

Swedish Orphan Biovitrum (Sobi), biopharmaceutical company, is supporting this research study by providing the study drugs and funding.

Avatrombopag vs. Placebo for CIT in GI Malignancies

A Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase 2 Study of Avatrombopag for Persistent Chemotherapy-Induced Thrombocytopenia in Patients With Gastrointestinal Malignancies (ACT-GI)

The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: \[contact information for Sponsor Investigator or designee\]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.

The primary endpoint of this study is the comparison of the response rate between the avatrombopag arm and the placebo arm. A response is defined as achieving a platelet count ≥100,000/µL within the 2 week lead-in period and then finishing at least 1 cycle of chemotherapy without CIT recurrence (no on-cycle dose-reduction or treatment delay due to thrombocytopenia and ability to receive another cycle of chemotherapy without dose-reduction or treatment delay, defined as platelet count of ≥100,000/µL at the start of the following cycle whether or not an additional cycle is planned).

Defined as the composite of successful initial platelet count recovery to ≥100,000/µL within 15 days of initiation of study drug, plus CIT prevention for one additional chemotherapy cycle (including at the completion of that cycle/start of the following cycle).

Assessed by the rate of initial platelet count recovery to ≥100,000/µL during the lead-in period

Assessed by the rate of initial platelet count recovery to ≥100,000/µL during the lead-in period.

The decision on platelet transfusion could be made either because the patient's platelet count is below a threshold, or due to physician's decision. The probability of patients requiring platelet transfusion will be estimated with a 95% confidence interval.

The rate of clinically relevant bleeding will be estimated by the Kaplan-Meier curve. Bleeding events will be graded according to CTCAE and according to the modified WHO bleeding scale. Clinically significant bleeding events will be considered grade II-IV events per this scale.

Thromboembolic events will be graded per CTCAE.

Swedish Orphan Biovitrum

Principal Investigator

Symptoms and General Pathology

Infections

Respiratory Tract (Lung and Bronchial) Diseases

Immune System Diseases

Heart and Blood Diseases

Rare Diseases

Syndrome

Preleukemia

Myelodysplastic Syndromes

Anemia

Respiratory Tract Infections

Neutropenia

Purpura, Thrombocytopenic, Idiopathic

Hemolysis

Anemia, Hemolytic

Anemia, Hemolytic, Autoimmune

Purpura

Purpura, Thrombocytopenic

Bone Marrow Diseases

Precancerous Conditions

Agranulocytosis

Leukopenia

Leukocyte Disorders

Hemostatic Disorders

Blood Coagulation Disorders

Thrombotic Microangiopathies

Hemorrhagic Disorders

Autoimmune Diseases

Hemorrhage

Skin Manifestations

Chronic Graft Versus Host Disease

Granulocytopenia

Immune Thrombocytopenia

Idiopathic Thrombocytopenic Purpura

Autoimmune Hemolytic Anemia

Cold Agglutinin Disease

Antineoplastic Agents

Antirheumatic Agents

Hematinics

Coagulants

Rituximab

Luspatercept

Epoetin Alfa

Agglutinins

AIHA patients will be enrolled at diagnosis and stratified according to AIHA type (i.e. warm, cold, mixed, and atypical forms), sampled for peripheral blood for cytokine and NGS studies, and for feces for microbiome studies. If clinically indicated, bone marrow evaluation will be performed and a sample for single cell analysis will be collected. Patients will be followed up to collect treatments, responses, relapses, and complications (particularly thromboses and infections).

ITP patients will be enrolled at diagnosis and sampled for peripheral blood for cytokine and NGS studies, and for feces for microbiome studies. If clinically indicated, bone marrow evaluation will be performed and a sample for single cell analysis will be collected.Patients will be followed up to collect treatments, responses, relapses, and complications (particularly thromboses and infections).

CIN/AIN patients will be enrolled at diagnosis and sampled for peripheral blood for cytokine and NGS studies, and for feces for microbiome studies. If clinically indicated, bone marrow evaluation will be performed and a sample for single cell analysis will be collected.Patients will be followed up to collect treatments, responses, relapses, and complications (particularly infections).

MDS patients will be enrolled at diagnosis and sampled for peripheral blood for cytokine and NGS studies, and to evaluate red cell metabolism. If clinically indicated, bone marrow evaluation will be performed and a sample for single cell analysis will be collected. Patients will be followed up to collect treatments, responses, relapses, and outcome.

evaluation of immunomodulatory cytokines by ELISA kits on peripheral blood samples

cytokine essays

evaluation of somatic mutations commonly associated with myeloid neoplasm and immunodeficiencies by next generation sequencing on peripheral blood samples

evaluation of fecal microbiome on fecal samples

Fecal microbiome

evaluation of recombinant erythropoietin use, safety and efficacy in patients with autoimmune hemolytic anemia according to clinical practice

Erythropoietin

evaluation of cytokine levels, molecular profile and bone marrow microenvironment by single cell analysis in patients treated with luspatercept according to clinical practice

evaluation of TPO-RA use, safety and efficacy in patients with ITP according to clinical practice

Thrombopoietin Receptor Agonist

evaluation of G-CSF use, safety and efficacy in patients with CIN/AIN according to clinical practice

G-CSF

Bruno Fattizzo, MD

The goal of this observational study is to characterize the diagnostic and therapeutic management of autoimmune cytopenias including autoimmune hemolytic anemia, immune thrombocytopenia, and chronic idiopathic/autoimmune neutropenia.

The main aims to answer are:

* evaluation of traditional and novel diagnostic tools including immunohematology, cytokine essays, bone marrow studies, molecular findings, and fecal microbiome.
* evaluation of type and sequence of the therapies administered, the response rates, and the adverse events.
* evaluation of clinical and laboratory (immunologic, molecular, and morphologic) predictors of outcome.
* evolution of autoimmune cytopenias into myelodysplastic syndromes.
* a subgroup of patients with myelodysplastic syndromes will be included to evaluate the presence of immunologic events, autoimmune activation, and red cell metabolism.

Participants will receive a clinical/laboratory diagnostic workup as per current clinical practice. Furthermore They will be sampled at baseline (peripheral blood and feces for microbiome) and followed up for at least 3 years to evaluate their clinical course, therapeutic management and outcome.

This observational study will characterize the diagnostic and therapeutic management of autoimmune cytopenias including autoimmune hemolytic anemia, immune thrombocytopenia, and chronic idiopathic/autoimmune neutropenia to evaluate predictors of outcome. Additionally, a subgroup of patients with myelodysplastic syndromes (diagnosed according to current WHO 5th edition 2022) will be included to evaluate the presence of autoimmune activation, and red cell metabolism.

peripheral blood for cytokines and next generation sequencing, bone marrow sample for single cell analysis, fecal sample for microbiome

Prospective Evaluation of Diagnosis and Treatment of Patients With Autoimmune Cytopenias Including Autoimmune Hemolytic Anemia, Immune Thrombocytopenia, and Chronic Idiopathic/Autoimmune Neutropenia

Evaluation of the Diagnostic/Therapeutic Course of Patients With Autoimmune Cytopenias (Autoimmune Hemolytic Anemia AIHA, Immune Thrombocytopenia ITP, Chronic Idiopathic/Autoimmune Neutropenia CIN/AIN) and Identification of Predictive and Prognostic Markers.

to define the sensitivity of autoantibody testing in autoimmune cytopenias

to define the specificity of autoantibody testing in autoimmune cytopenias

to define the sensitivity of bone marrow trephine in autoimmune cytopenias

to define response rates to treatment of autoimmune cytopenias and myelodysplastic syndromes

to define somatic mutations in autoimmune cytopenias and myelodysplastic syndromes by NGS

to define pyruvate kinase activity in myelodysplastic syndromes

to define microbiome composition in autoimmune cytopenias and myelodysplastic syndromes

to define bone marrow composition by single cell analysis in autoimmune cytopenias and myelodysplastic syndromes

to define cytokine levels in autoimmune cytopenias and myelodysplastic syndromes by ELISA

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Avatrombopag vs. Placebo for CIT in GI Malignancies	NCT05772546	Gastrointestina... Gastrointestina... Chemotherapy-In...	Avatrombopag Matching Placeb...	18 Years -	Massachusetts General Hospital
Prospective Evaluation of Diagnosis and Treatment of Patients With Autoimmune Cytopenias Including Autoimmune Hemolytic Anemia, Immune Thrombocytopenia, and Chronic Idiopathic/Autoimmune Neutropenia	NCT05931718	Autoimmune Hemo... Immune Thromboc... Chronic Idiopat... Autoimmune Neut... Myelodysplastic... Cold Agglutinin...	cytokine essays NGS Fecal microbiom... Erythropoietin Luspatercept Thrombopoietin ... G-CSF	18 Years -	Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
Avatrombopag vs. Placebo for CIT in GI Malignancies	NCT05772546	Gastrointestina... Gastrointestina... Chemotherapy-In...	Avatrombopag Matching Placeb...	18 Years -	Massachusetts General Hospital
Prospective Evaluation of Diagnosis and Treatment of Patients With Autoimmune Cytopenias Including Autoimmune Hemolytic Anemia, Immune Thrombocytopenia, and Chronic Idiopathic/Autoimmune Neutropenia	NCT05931718	Autoimmune Hemo... Immune Thromboc... Chronic Idiopat... Autoimmune Neut... Myelodysplastic... Cold Agglutinin...	cytokine essays NGS Fecal microbiom... Erythropoietin Luspatercept Thrombopoietin ... G-CSF	18 Years -	Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
Avatrombopag vs. Placebo for CIT in GI Malignancies	NCT05772546	Gastrointestina... Gastrointestina... Chemotherapy-In...	Avatrombopag Matching Placeb...	18 Years -	Massachusetts General Hospital

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