Everolimus, Nelarabine, Cyclophosphamide, and Etoposide Phosphate in Treating Patients with Relapsed or Refractory T Cell Lymphoblastic Leukemia or Lymphoma

Active:	Yes
Cancer Type:	Hematopoietic Malignancies Lymphoma Non-Hodgkin Lymphoma Unknown Primary	NCT ID:	NCT03328104
Trial Phases:	Phase I	Protocol IDs:	AflacLL1602 (primary) NCI-2017-01717
Eligibility:	1 - 30 Years, Male and Female	Study Type:	Treatment
Study Sponsor:	Children's Healthcare of Atlanta - Egleston
NCI Full Details:	http://clinicaltrials.gov/show/NCT03328104

Summary

This pilot phase I trial studies the side effects and best dose of everolimus and to see how well it works when given together with nelarabine, cyclophosphamide, and etoposide phosphate in treating patients with T cell lymphoblastic leukemia or lymphoma that has come back (relapsed) or does not respond to treatment (refractory). Drugs used in chemotherapy, such as everolimus, nelarabine, cyclophosphamide, and etoposide phosphate, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.

Objectives

PRIMARY OBJECTIVE:
I. To determine the maximum tolerated dose (MTD) and describe the dose-limiting toxicity (DLT) of everolimus when given in combination with nelarabine, etoposide phosphate (etoposide) and cyclophosphamide to children with bone marrow relapse of T cell acute lymphoblastic leukemia (T-ALL) or relapsed T cell lymphoblastic lymphoma (T-LL).

SECONDARY OBJECTIVES:
I. To determine the pharmacokinetics of everolimus when given in combination with nelarabine, cyclophosphamide and etoposide.
II. To describe changes in phosphoprotein (pAkt and p4EBP1) and Mer expression at time points pre- and post everolimus therapy in peripheral blood mono-nuclear cells (PBMCs) and bone marrow.
III. To determine the response rate as defined by the ability to achieve complete remission (CR) after 1 and 2 courses of this therapy in children with bone marrow relapse of T-ALL or relapsed T cell lymphoblastic lymphoma (T-LLy).
IV. For patients that proceed to allogeneic stem cell transplantation, to determine the time from start of study treatment to transplant in patients with bone marrow relapse of T-ALL or relapsed T-LLy.

OUTLINE: This is a dose-escalation study of everolimus.

Patients receive everolimus orally (PO) once daily (QD) on days 1-28, nelarabine intravenously (IV) over 60 minutes on days 1-5, etoposide phosphate IV over 1 hour on days 1-5, and cyclophosphamide IV over 30-60 minutes on days 1-5. Patients may also receive methotrexate intrathecally (IT), therapeutic hydrocortisone IT, and cytarabine IT between days 29-36. Patients with stable disease or with partial/complete response after course 1 may receive a second course.

Treatment Sites in Georgia

Aflac Cancer and Blood Disorders Center of Children’s at Egleston
1405 Clifton Road NE
3rd Floor
Atlanta, GA 30322
404-785-0853
www.choa.org

**Clinical trials are research studies that involve people. These studies test new ways to prevent, detect, diagnose, or treat diseases. People who take part in cancer clinical trials have an opportunity to contribute to scientists’ knowledge about cancer and to help in the development of improved cancer treatments. They also receive state-of-the-art care from cancer experts... Click here to learn more about clinical trials.