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


Phase 1
12 Years
N/A
Open (Enrolling)
Both
Leukemia, Lymphoma

Thank you

Trial Information

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


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.

Inclusion 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

Type of Study:

Interventional

Study Design:

Primary Purpose: Treatment

Outcome Measure:

Dose-limiting toxicity

Safety Issue:

Yes

Principal Investigator

Arthur E. Frankel, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Scott and White Hospital & Clinic

Authority:

Unspecified

Study ID:

CDR0000640379

NCT ID:

NCT00889408

Start Date:

April 2009

Completion Date:

Related Keywords:

  • Leukemia
  • Lymphoma
  • 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
  • Waldenström 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
  • recurrent grade 3 follicular lymphoma
  • recurrent mantle cell lymphoma
  • recurrent marginal zone lymphoma
  • recurrent small lymphocytic lymphoma
  • extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
  • nodal marginal zone B-cell lymphoma
  • splenic marginal zone lymphoma
  • recurrent childhood grade III lymphomatoid granulomatosis
  • recurrent childhood large cell lymphoma
  • recurrent childhood lymphoblastic lymphoma
  • recurrent childhood small noncleaved cell lymphoma
  • childhood Burkitt lymphoma
  • intraocular lymphoma
  • noncutaneous extranodal lymphoma
  • prolymphocytic leukemia
  • Leukemia
  • Lymphoma
  • Lymphoma, Large-Cell, Immunoblastic

Name

Location
Masonic Cancer Center at University of Minnesota Minneapolis, Minnesota  55455
M. D. Anderson Cancer Center at University of Texas Houston, Texas  77030-4009
Scott and White Cancer Institute Temple, Texas  76508