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

STATUS

Recruiting
End date

Dec 19, 2022
participants needed

60
sponsor

Emory University

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Updated on 19 April 2022

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platelet count

corticosteroids

filgrastim

monoclonal antibodies

biologic agent

nitrosoureas

sargramostim

growth factor

erythropoietin

dexamethasone

metastasis

neutrophil count

malignant glioma

abemaciclib

platelet transfusion

myelosuppressive chemotherapy

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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 Identifier	NCT02644460
Sponsor	Emory University
Last Modified on	19 April 2022

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