A Study of Romiplostim to Prevent Low Platelet Counts in Children and Young Adults Receiving Chemotherapy for Solid Tumors
Condition: Solid Tumor; Solid Tumor, Childhood; Solid Carcinoma
MeSH terms: Neoplasms
Intervention: Romiplostim
Intervention description: Participants will receive weekly doses of romiplostim, beginning with cycle 4. The initial romiplostim dose will be 10 mcg/kg, and subsequent doses w ill vary based on chemotherapy regimen for a target of platelet count > 75,000- 200,000/mcL. Participants will continue romiplostim until completion of MAP or D9803, as defined above. Maximum romiplostim dose is 10 mcg/kg. Participants will be followed until 6 months after the last dose of romiplostim.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 2.0
Sex: All
Minimum age: 1 Year
Maximum age: 21 Years
Healthy volunteers: No
Keywords: romiplostim; primary solid tumor; Solid tumor; Solid tumor, childhood; Childhood solid tumor; Pediatric Solid Tumors; 20-467; Memorial Sloan Kettering Cancer Center

Summary:

      The purpose of this study is to find out whether romiplostim can help prevent low platelet
      counts caused by N8 or EFT chemotherapy, reduce the number of platelet transfusions required
      during chemotherapy, and prevent treatment delays due to low platelet counts.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Documented diagnosis of a primary solid tumor. Patients must have histological
             verification of malignancy at MSKCC.

          -  Male and female patients aged 1-21 years with a primary solid tumor undergoing
             treatment with the pre-defined chemotherapy regimens of EFT, MAP, D9803. Prior to
             enrollment patient could have been undergoing induction therapy with a similarly
             myelosuppressive regimen as long as they will be continuing with EFT, MAP, D9803 at
             the time of study enrollment.

          -  Patients undergoing treatment with MAP chemotherapy w ho have had ≥ 1 platelet
             transfusion during induction stage of treatment.

          -  Total Bilirubin (sum of conjugated + unconjugated) ≤ 3 times institutional upper limit
             of normal (ULN) for age and ALT/AST ≤ 3 times institutional ULN for age.

          -  Normal cardiac function:

               -  Shortening fraction greater than or equal to 28% by echocardiogram OR Left
                  ventricular ejection fraction (LVEF) greater than or equal to 50% on technetium-
                  99m pertechnetate radionuclide cineangiography (MUGA) or echocardiogram.

               -  Screening ECG with corrected QT (QTc) interval of < 470 msec.

               -  Timing of cardiac assessment: We will utilize the most recent EKG/ECHO when
                  assessing cardiac function. See section 9.0 for additional details.

          -  Adequate renal function, defined as an estimated Creatinine Clearance or GFR >40ml/min
             or an normal creatine for age (see below)

        Serum Creatinine by age:

        Age (years) <6: Maximum Serum Creatinine (mg/dL), Male 0.8, Female 0.8 Age (years) 6 to
        <10: Maximum Serum Creatinine (mg/dL), Male 1, Female 1 Age (years) 10 to <13: Maximum
        Serum Creatinine (mg/dL), Male 1.2, Female 1.2 Age (years) 13 to <16: Maximum Serum
        Creatinine (mg/dL), Male 1.5, Female 1.4 Age (years) >16: Maximum Serum Creatinine (mg/dL),
        Male 1.7, Female 1.4

        These threshold creatine values were derived from the Scwartz formula estimating GFR,
        utilizing child length and statured published by the CDC.

        Exclusion Criteria:

          -  Patients with history of hematologic malignancies or allogenic/autogenic stem cell
             transplant.

          -  Patients with a currently known predisposition to a myeloid stem cell disorder,
             myeloid leukemia, and/or bone marrow failure syndrome including, but not limited to:

               -  Aplastic anemia

               -  Ataxia telangiectasia

               -  Bloom syndrome

               -  Congenital amegakaryocytic thrombocytopenia

               -  Cyclic neutropenia

               -  Diamond Blackfan anemia

               -  Dyskeratosis congenita

               -  Familial AML/MDS syndromes (including ANKRD26, CEBPA, DDX41, ETV6, GATA2, RUNX1,
                  SRP72)

               -  Fanconi anemia

               -  Kostmann disease

               -  Li-Fraumeni syndrome

               -  Neurofibromatosis

               -  Nijmegen breakage syndrome

               -  Noonan syndrome

               -  Paroxysmal nocturnal hemoglobinuria

               -  Pearson syndrome

               -  Poland syndrome

               -  Rothmund-Thomson syndrome

               -  Severe congenital neutropenia

               -  Thrombocytopenia absent radii syndrome

               -  Trisomy 8

               -  Trisomy 21

               -  WHIM syndrome

               -  Wiskott Aldrich syndrome

               -  Xeroderma pigmentosa

          -  Secondary malignancy in the past 5 years.

          -  Patients who have previously undergone up-front chemotherapy and have relapsed or
             progressed through therapy.

          -  Patients who have received 4 or more cycles of induction chemotherapy for their
             current malignancy prior to time of enrollment.

          -  Previous use of romiplostim, eltrombopag, recombinant human TPO, or any other TPO
             receptor agonist, or any investigational platelet producing agent.

          -  Patients receiving other investigational agents are not eligible for study entry.

        History of uncontrolled arrhythmias, clinically significant electrocardiogram (ECG)
        abnormalities, active heart failure or pericardial disease.

          -  Patients with current or prior venous thrombotic event or arterial thrombotic event at
             time of enrollment will be ineligible for this study.

          -  Pregnant women/lactating mothers.

          -  Patients unwilling to use effective contraception method, which includes abstinence.

          -  Patients with an inability to return for follow-up visits or obtain follow-up studies
             required to assess toxicity to therapy.