Pharmacokinetic (PK) and Pharmacodynamic (PD) Study of Nelarabine in Patients With Relapsed/Refractory Lymphoid Malignancies

NCT01094860 | Completed Phase 1 FDA Drug

• 2 other identifiers: 2009-0717NCI-2010-01659
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of the clinical research study is to find the highest tolerable dose of nelarabine when given as a continuous infusion to patients with a lymphoid malignancy that has not responded to, or has come back after treatment with chemotherapy. The safety of this drug will also be studied.

Conditions

Leukemia

Keywords

Relapsed/Refractory Lymphoid Malignancies; Chronic lymphocytic leukemia; CLL; Small lymphocytic lymphoma; SLL; B-prolymphocytic leukemia; Follicular lymphoma; Mantle cell lymphoma; Lymphoplasmacytoid lymphoma; Marginal zone lymphoma; T-cell prolymphocytic leukemia; large granular lymphocyte leukemia; mycosis fungoides; Sezary syndrome; peripheral T-cell lymphoma; Chemotherapy; Monoclonal antibody therapy; T-cell or B-cell acute lymphoblastic leukemia (ALL); Continuous Infusion Nelarabine; Arranon

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD) of a 5-day Continuous Infusion Schedule of Nelarabine

  MTD defined as the highest dose that no more than 1 dose limiting toxicity (DLT) occurs among 6 patients. Dose-limiting toxicity (DLT) defined based on drug related events only. DLT in the first treatment cycle used for the dose escalation.

  28 day cycle

Study Arms (1)

Continuous Infusion Nelarabine

EXPERIMENTAL

Starting dose 200 mg/m2 x 5 days

Drug: Nelarabine

Interventions

Nelarabine DRUG

Starting dose 200 mg/m2 for 5 day continuous infusion administered via a central catheter, repeated every 28 days.

Also known as: Arranon

Continuous Infusion Nelarabine

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have one of the following relapsed/ refractory lymphoid malignancies: Chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL) or B-prolymphocytic leukemia which has been previously treated with a purine analog, and are not candidates for higher priority clinical studies. Follicular lymphoma, mantle cell lymphoma, lymphoplasmacytoid lymphoma or marginal zone lymphoma which has been previously treated with autologous or allogeneic stem cell transplantation.
• Continued from #1:T-cell prolymphocytic leukemia, large granular lymphocyte leukemia, mycosis fungoides / Sezary syndrome or peripheral T-cell lymphoma which has been previously treated with at least one line of chemotherapy or monoclonal antibody therapy. T-cell or B-cell acute lymphoblastic leukemia (ALL) which has been previously treated with at least one line of chemotherapy.
• Patients (both pediatrics and adults) must have adequate renal function (calculated creatinine clearance \>/= 50ml/min). For adults this will be calculated per the Cockcroft -Gault formula and in pediatric cases this will be calculated per the Schwartz formula.
• Patients must have adequate hepatic function (bilirubin \</= 2 mg/dL; SGOT or SGPT \</= 3X the ULN for the reference lab unless due to leukemia).
• Patients must have adequate marrow function (neutrophils \>/= 0.5x10\^9/L and platelets \>/= 50x10\^9/L) unless cytopenias are deemed due to disease.
• Patients must have adequate performance status (Zubrod 0-2).
• Female patients must not be pregnant or lactating. Female patients of childbearing potential (including those \<1 year postmenopausal) and male patients must agree to use contraception.
• Patients must sign an informed consent form indicating that they are aware of the investigational nature of this study, in keeping with the policies of the hospital.

You may not qualify if:

• Patients must not have untreated or uncontrolled life-threatening infection.
• Patients known to be HIV positive or known to have Hepatitis B and/or C are excluded.
• Patients must not have received systemic chemotherapy or monoclonal antibody therapy within 2 weeks of study enrollment. Patients who have previously received bolus nelarabine are still eligible. Hydroxyurea or corticosteroids for control of blood counts is allowed, but must be discontinued 24 hours prior to initiating nelarabine.
• Patients must not have a history of grade \>/=2 neurological toxicity with previous treatment, or persistent grade \>/=2 peripheral neuropathy. Drowsiness and lethargy were exempted from this criteria unless previously persistent for more than one week.
• Patients must not have uncontrolled central nervous system disease. Patients with a history of seizure disorders must be seizure-free for one year prior to enrolment.
• Patients must not have any other medical condition, including mental illness or substance abuse, deemed by the Investigator to be likely to interfere with a patient's ability to give informed consent or cooperate and participate in the study or interfere with the interpretation of the results.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• GlaxoSmithKline: collaborator

Study Sites (1)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Boddu PC, Senapati J, Ravandi-Kashani F, Jabbour EJ, Jain N, Ayres M, Chen Y, Keating MJ, Kantarjian HM, Gandhi V, Kadia TM. A phase 1 study to evaluate the safety, pharmacology, and feasibility of continuous infusion nelarabine in patients with relapsed and/or refractory lymphoid malignancies. Cancer. 2023 Feb 15;129(4):580-589. doi: 10.1002/cncr.34570. Epub 2022 Nov 29.

  PMID: 36448227 DERIVED

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Leukemia; Recurrence; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Prolymphocytic, B-Cell; Lymphoma, Follicular; Lymphoma, Mantle-Cell; Waldenstrom Macroglobulinemia; Lymphoma, B-Cell, Marginal Zone; Leukemia, Prolymphocytic, T-Cell; Leukemia, Large Granular Lymphocytic; Mycosis Fungoides; Sezary Syndrome; Lymphoma, T-Cell, Peripheral; Leukemia, Biphenotypic, Acute

Interventions

nelarabine

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Leukemia, B-Cell; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Leukemia, Prolymphocytic; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Lymphoma, B-Cell; Leukemia, T-Cell; Lymphoma, T-Cell, Cutaneous; Lymphoma, T-Cell

Study Officials

• Tapan Kadia, MD

  M.D. Anderson Cancer Center

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 25, 2010
• First Posted: March 29, 2010
• Study Start: June 8, 2010
• Primary Completion: August 9, 2018
• Study Completion: August 9, 2018
• Last Updated: February 11, 2020

Record last verified: 2020-02

Locations

US (1)