Bone Marrow Failure DisordersEarly Phase 1NCT04478227
TPO-Mimetic Use in Children for Hematopoietic Failure
A Early Phase 1 study testing Romiplostim in people with Bone Marrow Failure Disorders and Aplastic Anemia, run by Anjali Sharathkumar at 1 site in United States.
Trial summary
This is an open label, prospective Pilot interventional study will investigate the safety and efficacy of Romiplostim, thrombopoietin (TPO) mimetic, in children (ages: 0 to 21 years) with broad scope of bone marrow failure disorders including acquired and inherited conditions as a first line of therapy along with… Read more about this study
- Who is it for?
- Ages 0 to 21 years
- Conditions the study is for
- Bone Marrow Failure Disorders, Aplastic Anemia, Thrombocytopenia
- What is being tested?
- Romiplostim
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteUnited States
- Study dates
- 18 Aug 2020to 18 Jan 2024
- Phase
- Early Phase 1
- 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 0 to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Age ≥ 0 to ≤ 21 years
- Child should be receiving ongoing care with pediatric hematology/oncology providers
- Those enrolled in Arm A of the study should have a confirmed diagnosis of any of the following
- aplastic anemia i. Diagnosis of severe Aplastic anemia (newly diagnosed or refractory based on history of prior treatments) is established if Bone marrow cellularity <25% or and at least two of the following criteria are met:- (i) absolute neutrophil count less than 0.5 × 10^9/L, (ii) platelet count less than 20 × 10^9/L, and (iii) reticulocyte count less than 20 × 10^9/L ii. Moderate aplastic anemia is defined as bone marrow cellularity <50 percent and depression of at least two out of three blood counts below the normal values: criteria are met:- (i) absolute neutrophil count less than 1.2x10^9/m3, (ii) platelet count less than 70x10^9/L, and (iii) anemia with hemoglobin less than or equal to 8.5 g/dL and absolute reticulocyte count less than or equal to 60x10^9/L in transfusion-dependent patients but not fulfilling the criteria of severe aplastic anemia
- refractory cytopenia of childhood without monosomy 7 or 5q- and without an evidence of cytogenetic abnormality with predisposition to leukemia
- myelo-suppression contributing to severe pancytopenia (absolute neutrophil count <0.5 x 10^3/mm^3; platelet count less than 20 × 10^9/L, and reticulocyte count less than 20 × 10^9/L secondary to any other drug or infection
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- diagnosis of inherited bone marrow failure without chromosomal fragility disorder
- Those enrolled in Arm B of the study should have a confirmed diagnosis of any of the following:
- myelo-suppression specifically thrombocytopenia as defined by primary oncologist in children with solid tumors secondary to chemotherapy or radiation therapy contributing to delay in chemotherapy
- patient undergoing stem cell transplantation and experiencing persistent thrombocytopenia. This will include children not requiring platelet transfusions with a platelet count of <10 x 109/L, as well as those requiring platelet transfusions (transfusion dependent) for prevention of bleeding diathesis regardless of their platelet count at the time of recruitment (note: due to delayed engraftment these patients may have a higher platelet count because of platelet transfusion needs at the time of recruitment).
- Adequate organ function within 7 days of enrollment defined as:
- Creatinine: ≤ 2.0 mg/dL
- Hepatic function:
- For arm A, elevation of liver enzymes is acceptable for patients with hepatitis induced SAA as long as patient does not have history of chronic liver problem. If necessary, liver biopsy will be performed.
- For Arm B, elevation of liver enzymes will be accepted as long as no chronic liver problem. Liver biopsy will be performed if necessary.
- Females of childbearing potential agree to use effective contraception during the study period and for 4 months after completion of therapy
- Must be able to provide written and voluntary informed consent.
Who cannot join
- Gestational age < 32 weeks or Age > 21 years at the time of study enrolment
- Preexisting condition with predisposition for thrombosis
- Diagnosis of bone marrow failure syndrome with cancer predisposition including chromosomal fragility disorders (Fanconi anemia, Bloom syndrome, Ataxia Telangiectasia) and other conditions with known association towards cancer predisposition
- Presence of complex karyotype or monosomy 7 or 5q- or other cytogenetic abnormality with known predisposition to cancer.
- Diagnosis of MDS with excess blasts in transformation
- Female subjects who are nursing or pregnant (positive serum or urine β-human chorionic gonadotropin [β-hCG] pregnancy test) at screening or pre-dose on Day 1.
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- Current alcohol or drug abuse.
- Treatment with an investigational drug within 30 days or 5 half-lives (whichever is longer) preceding the first dose of study medication.
- Active and uncontrolled infections (e.g. sepsis, hepatitis B, hepatitis C).
- Chronic liver disease ie. Fibrosis or cirrhosis
- Subjects infected with Human Immunodeficiency Virus (HIV).
- Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to Romiplostim that contraindicates the subjects' participation
- Known history of sensitivity or allergy to the active substance, to any of the excipients, or to any E. coli-derived product.
- Moribund status or concurrent hepatic, renal, cardiac, neurologic, pulmonary, infectious, or metabolic disease of such severity that it would preclude the patient's ability to tolerate protocol therapy, or that death within 7-10 days is likely.
- Subjects who have participated in any study using an investigational drug during the previous 30 days.
- Non-English-speaking families who cannot speak or read English
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Iowa Hospitals & Clinics
Iowa City, Iowa, 52242
About this study
Official title: Single Arm Prospective Open Label Pilot Study Evaluating Short-Term Safety and Efficacy of Romiplostim in Children With Inherited and Acquired Disorders of Hematopoietic Failure
This is an open label, prospective Pilot interventional study will investigate the safety and efficacy of Romiplostim, thrombopoietin (TPO) mimetic, in children (ages: 0 to 21 years) with broad scope of bone marrow failure disorders including acquired and inherited conditions as a first line of therapy along with standard of care.
Read the detailed description
This investigator-initiated study will investigate the safety and efficacy of Romiplostim, thrombopoietin (TPO) mimetic, in children (ages: 0 to 21 years) with broad scope of bone marrow failure disorders (BMF) including acquired and inherited conditions as a first line of therapy along with standard of care.
Objectives: Primary objectives are to evaluate safety and preliminary efficacy of Romiplostim in children with BMF. Methods: This open label, prospective Pilot interventional study has two arms.
Arm A will include acquired bone marrow failure (BMF) disorders including aplastic anemia, refractory cytopenia of childhood without monosomy 7 and 5q deletion abnormalities, toxin induced myelosuppression due to infection and inherited cytopenia with or without involvement of other cell lines who are transfusion dependent and or showing progression to bone marrow failure. Arm B will include children with chemo and or radiotherapy induced thrombocytopenia/cytopenia and children undergoing stem cell transplantation (SCT). Children with cancer predisposition and other morbidities which are considered significant by the investigator will be excluded from the study.
- Conditions
- Bone Marrow Failure Disorders, Aplastic Anemia, Thrombocytopenia, Refractory Cytopenia of Childhood, Myelodysplastic Syndrome(MDS)
- Being tested
- Romiplostim
- Medical subject headings
- Bone Marrow Failure Disorders, Anemia, Aplastic, Thrombocytopenia, Myelodysplastic Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RomiplostimDrug
Also called Nplate
Nplate is a thrombopoietin receptor agonist indicated for the treatment of thrombocytopenia in patients with chronic immune (idiopathic) thrombocytopenic purpura (ITP) who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy.
| Study group | Role | What they receive |
|---|---|---|
| Arm A | Experimental | Arm A will include acquired bone marrow failure (BMF) disorders including aplastic anemia, refractory cytopenia of childhood/Myelodysplastic Syndrome(MDS) without monosomy 7 and 5q deletion abnormalities, toxin induced myelosuppression due to infection and inherited cytopenia with or without involvement of other cell lines who are transfusion dependent and or showing progression to bone marrow failure.
Arm A: Start at 5 microgram/kg/dose per week along with standard of care and escalate with 2.5 microgram/kg/dose increments (per week at physician's discretion depending on the clinical and laboratory response) (Maximum: 20 microgram/kg/dose) based on response for at least 24 weeks or until hematopoietic response is seen, whichever comes first. If patient shows response, therapy will be continued for a total of 52 weeks. Receives: Drug: Romiplostim |
| Arm B | Experimental | Arm B will include children with chemo and or radiotherapy induced thrombocytopenia/cytopenia and children undergoing stem cell transplantation (SCT).
Arm B: Starting dose 2 microgram/kg/dose per week with increments at 1 microgram/kg/dose (Maximum: 10 micrograms/kg/dose) depending on the laboratory response. Receives: Drug: Romiplostim |
What is being measured
The primary outcome is the main question the study is designed to answer.
Occurrence of treatment-related adverse events (AEs) according to NCI CTCAE v5.0
Categorize and quantify AEs per CTCAE version 5.0
Measured: During treatment and through 90 days following discontinuation of treatment
To estimate preliminary efficacy of Romiplostim as measured by improvement in hematopoiesis
Improvement in at least one of the cell blood lineages by 24 weeks of therapy:
- Platelet response (increase to 10 X 103/mL above baseline or stable platelet counts with transfusion independence for a minimum of 2 weeks in those who were transfusion dependent on entry into the protocol)
- Erythroid response (when pretreatment hemoglobin was, below 7 g/dL, defined as an increase in hemoglobin by 1.5 g/dL or, in transfused patients, a reduction in the units of packed red blood cell transfusions by an absolute number of at least 4 transfusions for 8 consecutive weeks, compared with the pretreatment transfusion number in the previous 8 weeks)
- Neutrophil response (when pretreatment absolute neutrophil count [ANC] of 0.5 x103 /mL as at least a 100% increase in ANC, or an ANC increase by 0.5 x103 /mL)
Measured: By 24 weeks of therapy
Secondary outcomes (7)
To assess time to hematological response
Time from Romiplostim initiation to response, as defined in Outcome 2, for each cell lineage
Measured: Time from Romiplostim initiation to response, by 24 weeks of therapy
To assess longitudinal changes in blood counts
Change in blood counts from Romiplostim initiation until the end of treatment
Measured: From treatment beginning to end, up to 52 weeks
To assess the incidence of bleeding (including muco-cutaneous bleeding)
Occurrences of bleeding as defined by the International Society of Haemostasis and Thrombosis Bleeding Assessment Tool (https://bleedingscore.certe.nl/)
Measured: From treatment beginning to end, up to 52 weeks
To assess the incidence of neutropenic fever
Number of occurrences of neutropenic fever
Measured: From treatment beginning to end, up to 52 weeks
To assess the requirement of blood product support
Change in number of platelet and red call transfusions without active bleeding diathesis
Measured: Prior to initiation of treatment through end of treatment, up to 52 weeks
To assess development of bone marrow myelofibrosis
Increase in bone marrow myelofibrosis as measured by reticulin staining of bone marrow biopsy at diagnosis and follow up bone marrow testing upon initiation of Romiplostim
Measured: at 3 to 6 months after treatment initiation; within 4 to 6 weeks after discontinuation of treatment or any other time-point if deemed clinically indicated
To assess transfusion dependence or decreased platelet transfusion requirement among subjects who receive pretreatment platelet transfusion
Number of patients who are transfusion dependent or who require decreased platelet transfusion
Measured: Up to 24 weeks after treatment initiation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jul 2020
- Study start18 Aug 2020
- Primary completion18 Jan 2024
- Study completion18 Jan 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Bone Marrow Failure DisordersStudies of the same condition, open and under way.
- 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
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Anjali Sharathkumar
- Sponsor type
- University, hospital or other
- Collaborators
- Amgen
- Responsible party
- Sponsor-investigator, Anjali Sharathkumar, University of Iowa
- Investigators
- Anjali A. Sharathkumar, MBBS, MD, MS, Principal investigator, University of Iowa
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04478227
- Sponsor's protocol ID
- 202004776
- Status last verified
- Jul 2024
- First submitted
- 10 Jul 2020
- Last updated
- 30 Jul 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Single Arm Prospective Open Label Pilot Study Evaluating Short-Term Safety and Efficacy of Romiplostim in Children With Inherited and Acquired Disorders of Hematopoietic Failure
- ClinicalTrials.gov ID
- NCT04478227
- Acronym / sponsor ID
- 202004776
- Conditions
- Bone Marrow Failure Disorders, Aplastic Anemia, Thrombocytopenia, Refractory Cytopenia of Childhood, Myelodysplastic Syndrome(MDS)
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Anjali SharathkumarUniversity, hospital or other
- Collaborators
- Amgen
- Study start
- 18 Aug 2020 (actual)
- Primary completion
- 18 Jan 2024 (actual)
- Study completion
- 18 Jan 2024 (actual)
- First posted
- 20 Jul 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.
This is an open label, prospective Pilot interventional study will investigate the safety and efficacy of Romiplostim, thrombopoietin (TPO) mimetic, in children (ages: 0 to 21 years) with broad scope of bone marrow failure disorders including acquired and inherited conditions as a first line of therapy along with standard of care.
Detailed description
This investigator-initiated study will investigate the safety and efficacy of Romiplostim, thrombopoietin (TPO) mimetic, in children (ages: 0 to 21 years) with broad scope of bone marrow failure disorders (BMF) including acquired and inherited conditions as a first line of therapy along with standard of care.
Objectives: Primary objectives are to evaluate safety and preliminary efficacy of Romiplostim in children with BMF. Methods: This open label, prospective Pilot interventional study has two arms.
Arm A will include acquired bone marrow failure (BMF) disorders including aplastic anemia, refractory cytopenia of childhood without monosomy 7 and 5q deletion abnormalities, toxin induced myelosuppression due to infection and inherited cytopenia with or without involvement of other cell lines who are transfusion dependent and or showing progression to bone marrow failure. Arm B will include children with chemo and or radiotherapy induced thrombocytopenia/cytopenia and children undergoing stem cell transplantation (SCT). Children with cancer predisposition and other morbidities which are considered significant by the investigator will be excluded from the study.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm A | Experimental | Drug: RomiplostimArm A will include acquired bone marrow failure (BMF) disorders including aplastic anemia, refractory cytopenia of childhood/Myelodysplastic Syndrome(MDS) without monosomy 7 and 5q deletion abnormalities, toxin induced myelosuppression due to infection and inherited cytopenia with or without involvement of other cell lines who are transfusion dependent and or showing progression to bone marrow failure. Arm A: Start at 5 microgram/kg/dose per week along with standard of care and escalate with 2.5 microgram/kg/dose increments (per week at physician's discretion depending on the clinical and laboratory response) (Maximum: 20 microgram/kg/dose) based on response for at least 24 weeks or until hematopoietic response is seen, whichever comes first. If patient shows response, therapy will be continued for a total of 52 weeks. |
| Arm B | Experimental | Drug: RomiplostimArm B will include children with chemo and or radiotherapy induced thrombocytopenia/cytopenia and children undergoing stem cell transplantation (SCT). Arm B: Starting dose 2 microgram/kg/dose per week with increments at 1 microgram/kg/dose (Maximum: 10 micrograms/kg/dose) depending on the laboratory response. |
Who may qualify
- Ages
- 0 to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (17 listed)
- Age ≥ 0 to ≤ 21 years
- Child should be receiving ongoing care with pediatric hematology/oncology providers
- Those enrolled in Arm A of the study should have a confirmed diagnosis of any of the following
- Those enrolled in Arm B of the study should have a confirmed diagnosis of any of the following:
- Adequate organ function within 7 days of enrollment defined as:
Key exclusion criteria (16 listed)
- Gestational age < 32 weeks or Age > 21 years at the time of study enrolment
- Preexisting condition with predisposition for thrombosis
- Diagnosis of bone marrow failure syndrome with cancer predisposition including chromosomal fragility disorders (Fanconi anemia, Bloom syndrome, Ataxia Telangiectasia) and other conditions with known association towards cancer predisposition
- Presence of complex karyotype or monosomy 7 or 5q- or other cytogenetic abnormality with known predisposition to cancer.
- Diagnosis of MDS with excess blasts in transformation
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 |
|---|---|---|
| RomiplostimAlso: NplateNplate is a thrombopoietin receptor agonist indicated for the treatment of thrombocytopenia in patients with chronic immune (idiopathic) thrombocytopenic purpura (ITP) who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy. | Drug | Arm A, Arm B |
Primary outcome
Occurrence of treatment-related adverse events (AEs) according to NCI CTCAE v5.0
Time frame: During treatment and through 90 days following discontinuation of treatment
Categorize and quantify AEs per CTCAE version 5.0
To estimate preliminary efficacy of Romiplostim as measured by improvement in hematopoiesis
Time frame: By 24 weeks of therapy
Improvement in at least one of the cell blood lineages by 24 weeks of therapy: 1. Platelet response (increase to 10 X 103/mL above baseline or stable platelet counts with transfusion independence for a minimum of 2 weeks in those who were transfusion dependent on entry into the protocol) 2. Erythroid response (when pretreatment hemoglobin was, below 7 g/dL, defined as an increase in hemoglobin by 1.5 g/dL or, in transfused patients, a reduction in the units of packed red blood cell transfusions by an absolute number of at least 4 transfusions for 8 consecutive weeks, compared with the pretreatment transfusion number in the previous 8 weeks) 3. Neutrophil response (when pretreatment absolute neutrophil count [ANC] of 0.5 x103 /mL as at least a 100% increase in ANC, or an ANC increase by 0.5 x103 /mL)
7 secondary outcomes
To assess time to hematological response
Time frame: Time from Romiplostim initiation to response, by 24 weeks of therapy
To assess longitudinal changes in blood counts
Time frame: From treatment beginning to end, up to 52 weeks
To assess the incidence of bleeding (including muco-cutaneous bleeding)
Time frame: From treatment beginning to end, up to 52 weeks
To assess the incidence of neutropenic fever
Time frame: From treatment beginning to end, up to 52 weeks
To assess the requirement of blood product support
Time frame: Prior to initiation of treatment through end of treatment, up to 52 weeks
To assess development of bone marrow myelofibrosis
Time frame: at 3 to 6 months after treatment initiation; within 4 to 6 weeks after discontinuation of treatment or any other time-point if deemed clinically indicated
To assess transfusion dependence or decreased platelet transfusion requirement among subjects who receive pretreatment platelet transfusion
Time frame: Up to 24 weeks after treatment initiation
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jul 2024.
- Individual participant dataSharing planned: No
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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.
Anjali A. Sharathkumar, MBBS, MD, MS principal investigator
University of Iowa
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Romiplostim in people with Bone Marrow Failure Disorders and Aplastic Anemia, run by Anjali Sharathkumar at 1 site in United States.
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 17 inclusion and 16 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: finished, as of the sponsor's last update on 30 Jul 2024. 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 United States. 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?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Occurrence of treatment-related adverse events (AEs) according to NCI CTCAE v5.0 (time frame: During treatment and through 90 days following discontinuation of treatment). 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 30 Jul 2024.