TPO Use in Children for Hemotopoietic Failure

Brief Title

TPO-Mimetic Use in Children for Hemotopoietic Failure

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

Brief 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 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 Phase

Early Phase 1

Study Type

Interventional


Primary Outcome

Occurrence of treatment-related adverse events (AEs) according to NCI CTCAE v5.0

Secondary Outcome

 To assess time to hematological response

Condition

Bone Marrow Failure Disorders

Intervention

Romiplostim

Study Arms / Comparison Groups

 Arm A
Description:  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.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

25

Start Date

August 18, 2020

Completion Date

December 3, 2022

Primary Completion Date

June 1, 2022

Eligibility Criteria

        Inclusion Criteria:

          -  Age 0 to 21 years

          -  Child should be receiving ongoing care with pediatric hematology/oncology providers

          -  Confirmed diagnosis of any of the following

               1. aplastic anemia

                    -  Diagnosis of severe Aplastic anemia 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 × 109/L, (ii) platelet count less
                       than 20 × 109/L, and (iii) reticulocyte count less than 20 × 109/L

                    -  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 1200/mm3,
                       (ii) platelet count less than 70,000/mm3, and (iii) anemia with hemoglobin
                       less than or equal to 8.5 g/dL and absolute reticulocyte count less than or
                       equal to 60,000/mm3 in transfusion-dependent patients but not fulfilling the
                       criteria of sever aplastic anemia

               2. refractory cytopenia of childhood without monosomy 7 or 5q- and without an
                  evidence of cytogenetic abnormality with predisposition to leukemia

               3. 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

               4. myelo-suppression contributing to severe pancytopenia (absolute neutrophil count
                  <0.5 x 0.5 × 109/L; platelet count less than 20 × 109/L, and reticulocyte count
                  less than 20 × 109/L secondary to any other drug or infection

               5. patient undergoing stem cell transplantation and experiencing persistent
                  thrombocytopenia (platelet count <10 x 109/L) requiring platelet transfusions

               6. diagnosis of inherited bone marrow failure without chromosomal fragility disorder

          -  Adequate organ function within 7 days of enrollment defined as:

               1. Creatinine: ≤ 2.0 mg/dL

               2. 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.

        Exclusion Criteria:

          -  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

          -  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.

          -  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
      

Gender

All

Ages

N/A - 21 Years

Accepts Healthy Volunteers

No

Contacts

Anjali A. Sharathkumar, MBBS, MD, MS, 319-356-1693, [email protected]

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT04478227

Organization ID

202004776


Responsible Party

Sponsor-Investigator

Study Sponsor

Anjali Sharathkumar

Collaborators

 Amgen

Study Sponsor

Anjali A. Sharathkumar, MBBS, MD, MS, Principal Investigator, University of Iowa


Verification Date

June 2021