Abemaciclib in Children With DIPG or Recurrent/Refractory Solid Tumors (AflacST1501)

  • STATUS
    Recruiting
  • End date
    Dec 19, 2022
  • participants needed
    60
  • sponsor
    Emory University
Updated on 19 April 2022
platelet count
corticosteroids
filgrastim
monoclonal antibodies
biologic agent
nitrosoureas
sargramostim
growth factor
erythropoietin
dexamethasone
metastasis
neutrophil count
malignant glioma
abemaciclib
platelet transfusion
myelosuppressive chemotherapy
nervous

Summary

This is a Phase I clinical trial evaluating abemaciclib (LY2835219), an inhibitor of cyclin dependent-kinases 4 and 6 (Cdk 4/6) in children and young adults with newly diagnosed diffuse intrinsic pontine glioma (DIPG) (Stratum A) and in relapsed/refractory/progressive malignant brain (Grade III/IV, including DIPG; MBT) and solid tumor (ST) patients (Stratum B).

Description

Stratum A- Appropriate dose RT will be administered in 30-33 fractions over approximately 6 weeks for Stratum A patients. Treatment with abemaciclib (LY2835219) will start on the same day as radiation therapy (RT) and continue twice daily during and after RT for a maximum treatment duration of 2 years. Investigators plan to treat a maximum of 4 cohorts of research participants (dosage levels 1, 2, 3, and 4) with escalating doses of abemaciclib (LY2835219) starting with dose level 1 (80% of adult dose). A cycle is defined as 28 days and the first 6 weeks of therapy will constitute the dose-limiting toxicity (DLT)-evaluation period. Participants must take abemaciclib by mouth as intact capsules.

Stratum B (no longer enrolling) - Abemaciclib (LY2835219) will be administered orally on a twice daily basis continuously for 28 days, which defines one cycle. The maximum treatment duration will be 2 years. Investigators plan to treat a maximum of 4 cohorts of research participants (dosage levels 1, 2, 3, and 4) with escalating doses of abemaciclib starting with dose level 1 (80% of adult dose). Dose escalation will be independent of Stratum A escalation. A cycle is defined as 28 days and the first 4 weeks of therapy will constitute the DLT-evaluation period. Participants must take abemaciclib by mouth as intact capsules.

Enrollment for Stratum B closed December 27, 2018.

Details
Condition Diffuse Intrinsic Pontine Glioma, Brain Tumor, Recurrent, Solid Tumor, Recurrent, Neuroblastoma, Recurrent, Refractory, Ewing Sarcoma, Recurrent, Refractory, Rhabdomyosarcoma, Recurrent, Refractory, Osteosarcoma, Recurrent, Refractory, Rhabdoid Tumor, Recurrent, Refractory
Treatment Abemaciclib
Clinical Study IdentifierNCT02644460
SponsorEmory University
Last Modified on19 April 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

Patient must have measurable or evaluable disease
Age must be ≥ 2 years and < 25 years
Body surface area (BSA) ≥ 0.5 m^2
Lansky (for participants ≤ 16 years) or Karnofsky (for participants > 16 years) performance score ≥ 40 at the time of study enrollment
Adequate organ function at the time of study enrollment as follows
Bone marrow: Absolute neutrophil count (ANC) ≥ 1,000/μL, platelet count ≥ 75,000/μL (transfusion independent for ≥ 7 days), hemoglobin concentration ≥ 8g/dL (may be transfused)
Patients with bone marrow metastatic disease who do not meet the above criteria will be eligible to enroll in the study with the following count criteria. These patients will not be evaluable for hematologic toxicity or hematologic DLT
ANC > 750/μL within 7 days prior to first dose of abemaciclib
Platelet count > 50,000/μL (may receive platelet transfusions) within 7 days prior to first dose of abemaciclib
Hemoglobin ≥ 7.5 g/dL (may receive red blood cell (RBC) transfusions) within 7 days prior to first dose of abemaciclib
Renal: Normal serum creatinine concentration based on age or glomerular
Hepatic: Total bilirubin concentration < 1.5x the institutional upper limit of normal for age; serum glutamic pyruvic transaminase (SGPT) < 10x the institutional upper limit of normal for patients on Stratum A. Stratum B patients must have SGPT < 4x the institutional upper limit of normal
filtration rate (GFR) > 70 ml/min/1.73m^2
Cardiac: Adequate cardiac conductivity with corrected Q-T interval (QTC) of < 450 ms on screening ECG
All patients should submit an archival tumor biopsy specimen (collected at diagnosis or relapse). Patients who have no tumor tissue available may be permitted to participate after discussion with the principal investigator
Female research participants of childbearing age must not be pregnant as confirmed by
Males or females of reproductive potential may not participate unless they have agreed to use two effective contraceptive methods. Abstinence in a non-sexually active child will be sufficient birth control
a serum or urine pregnancy test within 1 week of start of treatment
Inclusion Criteria for Stratum A (Newly Diagnosed DIPG)
Participants must not be breast-feeding
Diagnosis of DIPG or high-grade glioma originating from the brainstem
Participants have had no previous treatment except corticosteroid use
Inclusion Criteria for Stratum B (Recurrent/refractory/progressive MBT (including DIPG) or
ST) - Stratum B is closed to further accrual of participants
Patients must have radiologic evidence of recurrent, refractory or progressive
malignant central nervous system (WHO Grade III or IV) or solid tumor. For patients
with radiologic features of DIPG histologic confirmation of diagnosis is not required
though biopsy is suggested if clinically indicated
Patients with neurological deficits should have deficits that are stable for a minimum
of 1 week prior to registration
Patients who are on dexamethasone must be on a stable or decreasing dose for at least
one week prior to registration
Patients must have fully recovered from the acute toxic effects of chemotherapy
immunotherapy, or radiotherapy prior to entering this study
Myelosuppressive chemotherapy: Patients must have received their last dose of known
myelosuppressive anticancer chemotherapy at least 21 days prior to study registration
or at least six weeks if nitrosourea. At least two weeks must have lapsed if patients
received lower dose oral etoposide (50 mg/2) without experiencing evidence of
myelosuppression (i.e. neutropenia or requiring transfusion with blood products)
Biologic agent: Patient must have recovered from any toxicity potentially related to
the agent and received their last dose of the biologic agent ≥ 7 days prior to study
registration
Monoclonal antibody treatment: At least three half-lives must have elapsed prior to
registration
Radiation: Patient has received radiation therapy prior to study registration
Patients must have had their last fraction of local irradiation to the primary tumor ≥
months prior to registration, their last fraction of craniospinal irradiation
(>24Gy) or total body irradiation > 3 months prior to registration or > 6 wks for
therapeutic doses of metaiodobenzylguanidine (MIBG). Patient has not received focal
irradiation for symptomatic metastatic sites within 14 days prior to registration
Bone Marrow Transplant: Patient must be ≥ 3 months since high dose chemotherapy and
peripheral blood stem cell rescue prior to registration
Autologous stem cell transplant following myeloablative therapy within 3 months prior
to the first dose of abemaciclib or prior allogeneic stem cell transplant at any time
Patients who received stem cell reinfusion following non-myeloablative therapy are
eligible once they meet peripheral blood count criteria
Growth factors: Patients must be off all colony forming growth factors(s) for at least
week prior to registration (filgrastim, sargramostim, erythropoietin) and at least 2
weeks for long-acting formulations (e.g. Neulasta)

Exclusion Criteria

Patients with uncontrolled infection
Patients receiving any other anticancer or investigational drug therapy
Prior therapy with abemaciclib
Known mutation of Rb in tumor tissue
Prior history of QTC prolongation or QTC>450 ms on screening ECG
Patients with any concomitant significant medical illness that in the investigator's
opinion cannot be adequately controlled with appropriate therapy, or that would impair
the evaluation of side effects related to this treatment, alter drug metabolism or the
tolerance to this treatment
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