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

• 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 ]

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.

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.

• Leukemia
• Lymphoma

• Biological: anti-CD19/CD22 bispecific ligand-directed toxin DT2219ARL
• Other: flow cytometry
• Other: immunoenzyme technique
• Other: immunohistochemistry staining method
• Other: pharmacological study

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