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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by M.D. Anderson Cancer Center
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT01094860
First received: March 25, 2010
Last updated: July 14, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention Phase
Leukemia
Drug: Nelarabine
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Pharmacokinetic and Pharmacodynamic Study to Evaluate the Safety and Feasibility of Continuous Infusion Nelarabine in Patients With Relapsed / Refractory Lymphoid Malignancies

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Maximum Tolerated Dose (MTD) of a 5-day Continuous Infusion Schedule of Nelarabine [ Time Frame: 28 day cycle ] [ Designated as safety issue: Yes ]
    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.


Estimated Enrollment: 27
Study Start Date: June 2010
Estimated Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Continuous Infusion Nelarabine
Starting dose 200 mg/m2 x 5 days
Drug: Nelarabine
Starting dose 200 mg/m2 for 5 day continuous infusion administered via a central catheter, repeated every 28 days.
Other Name: Arranon

  Show Detailed Description

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. 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.
  2. 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.
  3. 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.
  4. Patients must have adequate hepatic function (bilirubin </= 2 mg/dL; SGOT or SGPT </= 3X the ULN for the reference lab unless due to leukemia).
  5. Patients must have adequate marrow function (neutrophils >/= 0.5x10^9/L and platelets >/= 50x10^9/L) unless cytopenias are deemed due to disease.
  6. Patients must have adequate performance status (Zubrod 0-2).
  7. 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.
  8. 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.

Exclusion Criteria:

  1. Patients must not have untreated or uncontrolled life-threatening infection.
  2. Patients known to be HIV positive or known to have Hepatitis B and/or C are excluded.
  3. 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.
  4. 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.
  5. 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 enrollment.
  6. 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01094860

Contacts
Contact: Tapan Kadia, MD 713-792-7305

Locations
United States, Texas
UT MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Principal Investigator: Tapan Kadia, MD         
Sponsors and Collaborators
M.D. Anderson Cancer Center
GlaxoSmithKline
Investigators
Study Chair: Tapan Kadia, MD UT MD Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT01094860     History of Changes
Other Study ID Numbers: 2009-0717, NCI-2010-01659
Study First Received: March 25, 2010
Last Updated: July 14, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by M.D. Anderson Cancer Center:
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

Additional relevant MeSH terms:
Neoplasms
Leukemia
Neoplasms by Histologic Type

ClinicalTrials.gov processed this record on September 16, 2014