DT2219ARL Immunotoxin in Treating Patients With B-Cell Leukemia or Lymphoma That Has Relapsed or Not Responded to Treatment - Full Text View

Sponsor:	Scott and White Hospital & Clinic
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00889408

Purpose

RATIONALE: Immunotoxins, such as DT2219ARL, can find certain cancer cells and kill them without harming normal cells.

PURPOSE: This phase I trial is studying the side effects and best dose of DT2219ARL immunotoxin in treating patients with B-cell leukemia or lymphoma that has relapsed or not responded to treatment.

Condition	Intervention	Phase
Leukemia Lymphoma	Biological: anti-CD19/CD22 bispecific ligand-directed toxin DT2219ARL Other: flow cytometry Other: immunoenzyme technique Other: immunohistochemistry staining method Other: pharmacological study	Phase I

Study Type:	Interventional
Study Design:	Treatment
Official Title:	A Phase I Study of DT2219ARL (IND #100780), a Bispecific Chain Immunotoxin for the Treatment of CD19(+), CD22 (+) B-Lineage Leukemia or Lymphoma

Resource links provided by NLM:

MedlinePlus related topics: Cancer Leukemia, Adult Acute Leukemia, Adult Chronic Leukemia, Childhood Lymphoma

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Dose-limiting toxicity [ Designated as safety issue: Yes ]
Toxicity profile [ Designated as safety issue: Yes ]
Maximum-tolerated dose [ Designated as safety issue: Yes ]
Clinical response rate (complete response [CR], partial response, marrow CR) [ Designated as safety issue: No ]
Anti-DT2219ARL antibodies at days 1, 7, 15, and 30 [ Designated as safety issue: No ]
Serum DT2219ARL levels and half-life [ Designated as safety issue: No ]
Pre-treatment leukemic blast and lymphoma cell CD19 and CD22 densities [ Designated as safety issue: No ]

Estimated Enrollment:	36
Study Start Date:	April 2009
Estimated Primary Completion Date:	April 2012 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Determine the toxicities and maximum-tolerated dose of anti-CD19/CD22 bispecific ligand-directed toxin DT2219ARL in patients with relapsed or refractory CD19+ and CD22+ B-lineage leukemia or lymphoma.
Determine the pharmacokinetic profile (PK) (Cmax, T1/2, AUC, Cl, Vd) of DT2219ARL.
Determine any therapeutic activity of DT2219ARL within the confines of a phase I study as determined by the change in percentage of blasts in bone marrow and peripheral blood and recovery of normal hematopoiesis.
Measure levels of human anti-DT2219ARL antibodies.
Determine if there is a correlation between PK parameters and toxicity or response.
Determine if the expression of the CD19 and CD22 cell surface antigens is affected by treatment with DT2219ARL using flow cytometric analysis of lymphoblasts in peripheral blood and bone marrow or immunohistochemistry of node biopsies.
Determine whether the CD19 and CD22 surface antigen expression on patient blasts or lymphoma cells correlate with response.

OUTLINE: This is a multicenter study.

Patients receive anti-CD19/CD22 bispecific ligand-directed toxin DT2219ARL IV over 4 hours on days 1, 3, 5, and 7 in the absence of disease progression or unacceptable toxicity.

Blood samples are collected at baseline and periodically during study for pharmacokinetic and immunologic studies. Bone marrow aspirates are collected at baseline and day 28 for CD19 and CD22 antigens expression by flow cytometric assays or enzyme immunoassays.

After completion of study therapy, patients are followed periodically.

Eligibility

Ages Eligible for Study:	12 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Histologically confirmed B-cell lineage leukemia or lymphoma
Presence of CD19 and/or CD22 on at least 50% of the lymphoblasts or lymphoma cells obtained via bone marrow aspirate, peripheral blood as determined by flow cytometry, or node biopsy
Relapsed or refractory disease meeting the following criteria:
- Refractory to conventional therapy and other therapies of higher priority
- Relapse after autologous or allogeneic bone marrow transplantation allowed
Leukemia patients must have peripheral blast count < 50,000/mm^3 (may be achieved via hydroxyurea cytoreduction)
No leukemic or infectious pulmonary parenchymal disease
No CNS leukemia
- CSF < 5 WBC/μL allowed

PATIENT CHARACTERISTICS:

ECOG performance status 0-2
Life expectancy > 12 weeks and < 6 months
Serum creatinine ≤ 1.5 times upper limit of normal (ULN)
Total bilirubin ≤ 1.5 times ULN
AST or ALT < 2.5 times ULN
Serum albumin ≥ 3.0 g/dL
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
Adequate cardiac function defined as an ejection fraction of ≥ 40% by MUGA scan or echocardiography
No uncontrolled systemic infection
No documented seizure disorder or abnormal neurological examination
No documented penicillin or cephalosporin allergies

PRIOR CONCURRENT THERAPY:

Recovered from prior therapy
- Patients who have recovered from prior therapy and have > 50% rise in peripheral blast count (confirmed twice) or > 50% growth of lymph nodes are immediately eligible
At least 2 weeks since prior chemotherapy
No other concurrent chemotherapy or radiotherapy
No concurrent intravenous immunoglobulin

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00889408

Locations

United States, Minnesota
Masonic Cancer Center at University of Minnesota	Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Clinical Trials Office - Masonic Cancer Center at University o 612-624-2620
United States, Texas
M. D. Anderson Cancer Center at University of Texas	Recruiting
Houston, Texas, United States, 77030-4009
Contact: Clinical Trials Office - M. D. Anderson Cancer Center at the U 713-792-3245
Scott and White Cancer Institute	Recruiting
Temple, Texas, United States, 76508
Contact: Clinical Trials Office - Scott and White Cancer Institute 800-882-4366

Sponsors and Collaborators

Scott and White Hospital & Clinic

National Cancer Institute (NCI)

Investigators

Principal Investigator:

Arthur E. Frankel, MD

Scott and White Hospital & Clinic

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Scott and White Cancer Institute ( Arthur E. Frankel )
Study ID Numbers:	CDR0000640379, S-WHITE-81714, DT2219ARL, IRB#00000706
Study First Received:	April 26, 2009
Last Updated:	April 26, 2009
ClinicalTrials.gov Identifier:	NCT00889408 History of Changes
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

refractory chronic lymphocytic leukemia
childhood diffuse large cell lymphoma
childhood grade III lymphomatoid granulomatosis
childhood immunoblastic large cell lymphoma
B-cell adult acute lymphoblastic leukemia
recurrent adult acute lymphoblastic leukemia
B-cell childhood acute lymphoblastic leukemia
recurrent childhood acute lymphoblastic leukemia
adult acute myeloid leukemia with 11q23 (MLL) abnormalities
adult acute myeloid leukemia with inv(16)(p13;q22)
adult acute myeloid leukemia with t(15;17)(q22;q12)
adult acute myeloid leukemia with t(16;16)(p13;q22)
adult acute myeloid leukemia with t(8;21)(q22;q22)
recurrent adult acute myeloid leukemia
recurrent childhood acute myeloid leukemia

secondary acute myeloid leukemia
B-cell chronic lymphocytic leukemia
relapsing chronic myelogenous leukemia
childhood chronic myelogenous leukemia
cutaneous B-cell non-Hodgkin lymphoma
recurrent adult grade III lymphomatoid granulomatosis
Waldenstrom macroglobulinemia
recurrent adult Burkitt lymphoma
recurrent adult diffuse large cell lymphoma
recurrent adult diffuse mixed cell lymphoma
recurrent adult diffuse small cleaved cell lymphoma
recurrent adult immunoblastic large cell lymphoma
recurrent adult lymphoblastic lymphoma
recurrent grade 1 follicular lymphoma
recurrent grade 2 follicular lymphoma

Additional relevant MeSH terms:

Lymphatic Diseases
Leukemia
Neoplasms
Immunoproliferative Disorders
Neoplasms by Histologic Type
Immunologic Factors

Immune System Diseases
Physiological Effects of Drugs
Lymphoproliferative Disorders
Lymphoma
Pharmacologic Actions
Immunotoxins

ClinicalTrials.gov processed this record on November 05, 2009