NCT00002765

Brief Summary

RATIONALE: Immunotoxins can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. PURPOSE: Phase I trial to study the effectiveness of LMB-2 immunotoxin in treating patients who have leukemia or lymphoma.

Trial Health

80
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Geographic Reach
1 country

2 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

Study Start

First participant enrolled

April 1, 1996

Completed
3.6 years until next milestone

First Submitted

Initial submission to the registry

November 1, 1999

Completed
3.5 years until next milestone

First Posted

Study publicly available on registry

May 6, 2003

Completed
Last Updated

April 29, 2015

Status Verified

March 1, 2003

First QC Date

November 1, 1999

Last Update Submit

April 28, 2015

Conditions

LeukemiaLymphoma

Keywords

recurrent adult Hodgkin lymphomastage IV cutaneous T-cell non-Hodgkin lymphomarecurrent cutaneous T-cell non-Hodgkin lymphomaWaldenström macroglobulinemiarecurrent adult acute myeloid leukemiarecurrent adult acute lymphoblastic leukemiarelapsing chronic myelogenous leukemiarefractory chronic lymphocytic leukemiarefractory hairy cell leukemiarecurrent small lymphocytic lymphomarecurrent grade 1 follicular lymphomarecurrent grade 2 follicular lymphomarecurrent grade 3 follicular lymphomarecurrent adult diffuse small cleaved cell lymphomarecurrent adult diffuse mixed cell lymphomarecurrent adult diffuse large cell lymphomarecurrent adult immunoblastic large cell lymphomarecurrent adult lymphoblastic lymphomarecurrent adult Burkitt lymphomastage I adult T-cell leukemia/lymphomastage II adult T-cell leukemia/lymphomastage III adult T-cell leukemia/lymphomastage IV adult T-cell leukemia/lymphomarecurrent adult T-cell leukemia/lymphomaprolymphocytic leukemiarecurrent mantle cell lymphomastage IV mycosis fungoides/Sezary syndromerecurrent mycosis fungoides/Sezary syndromerecurrent marginal zone lymphomaextranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissuenodal marginal zone B-cell lymphomasplenic marginal zone lymphoma

Interventions

LMB-2 immunotoxinBIOLOGICAL

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)
DISEASE CHARACTERISTICS: * Histologically confirmed Hodgkin's disease, non-Hodgkin's lymphoma, or leukemia in one of the following categories: * Adult T-cell leukemia or lymphoma (ATL) * No smoldering ATL * No limitation on prior therapy * Cutaneous T-cell lymphoma (CTCL) * Stages IB-III and failed at least 1 standard therapy * Stage IV regardless of prior therapy * Stages I-IV peripheral T-cell lymphoma * Relapsed after standard chemotherapy * Ineligible for or refused salvage chemotherapy or bone marrow transplantation (BMT) * B-cell non-Hodgkin's lymphoma (NHL) of any histology * Indolent stages II-IV NHL * Failed at least 1 standard therapy * Disease symptomatic and requiring treatment * Aggressive NHL * Relapsed after standard chemotherapy * Ineligible for or refused salvage chemotherapy or BMT * Chronic lymphocytic leukemia (CLL) * Rai stages III and IV or Binet stage C * Failed standard therapy and at least 1 salvage chemotherapy * Primary B-cell prolymphocytic leukemia or prolymphocytic transformation of CLL * Failed standard therapy and at least 1 salvage chemotherapy * Hairy cell leukemia * Failed standard and salvage chemotherapy * Ineligible for or refused further salvage chemotherapy or BMT * Acute myelogenous leukemia * Failed standard chemotherapy * Ineligible for or refused salvage chemotherapy or BMT * Stages II-IV Hodgkin's disease * Failed standard chemotherapy * Ineligible for curative salvage radiotherapy or chemotherapy * Ineligible for or refused BMT * Patients with leukemias or lymphomas not easily classified in above categories who have failed standard therapy and are ineligible for or have refused bone marrow transplant * Evidence of interleukin-2 receptor-alpha (IL2Ra) expression by one of the following: * Greater than 10% of malignant cells reactive with anti-Tac by immunohistochemistry * Greater than 10% of malignant cells from a particular site positive by FACS * Greater than 400 IL2Ra sites per malignant cell by radiolabeled anti-Tac binding * Soluble IL2Ra level greater than 1,000 U/mL (normal geometric mean 235, with 95% confidence levels of 112-502 U) * Hodgkin's disease with measurable disease not amenable to biopsy * No CNS disease requiring treatment * Malignant cells in CSF allowed if judged not to represent clinically significant leukemic or lymphomatous meningitis (as in CSF contamination by blood) PATIENT CHARACTERISTICS: Age: * 18 and over Performance status: * Karnofsky 50-100% Life expectancy: * Greater than 2 months Hematopoietic: * Absolute neutrophil count greater than 1,000/mm3\* * Platelet count greater than 50,000/mm3\* NOTE: \*nonleukemic patients Hepatic: * AST and ALT less than 5 times normal Renal: * Creatinine less than 2.0 mg/dL OR * Creatinine clearance greater than 50 mL/min Pulmonary: * FEV1, TLC, and DLCO greater than 50% of predicted if pulmonary or mediastinal involvement with tumor greater than one third of total thoracic diameter Other: * HIV negative * Not pregnant * Fertile patients must use effective contraception * Serum must neutralize no more than 75% LMB-2 in tissue culture PRIOR CONCURRENT THERAPY: Biologic therapy: * See Disease Characteristics * At least 3 weeks since prior interferon Chemotherapy: * See Disease Characteristics * At least 3 weeks since prior cytotoxic chemotherapy * At least 3 weeks since prior retinoids * No concurrent chemotherapy Endocrine therapy: * No concurrent corticosteroids unless begun at least 3 weeks prior to entry and dose not increased during 3 weeks prior to entry Radiotherapy: * See Disease Characteristics * At least 3 weeks since prior whole-body electron beam radiotherapy * Other radiotherapy allowed within 3 weeks of entry provided less than 10% of marrow irradiated and measurable disease exists outside radiation port Surgery: * Not specified Other: * See Disease Characteristics * At least 3 weeks since any prior systemic therapy * No other concurrent investigational agents

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

Study Sites (2)

Laboratory of Molecular Biology

Bethesda, Maryland, 20892, United States

Location

Medicine Branch

Bethesda, Maryland, 20892, United States

Location

Related Publications (5)

  • Matsushita K, Margulies I, Onda M, Nagata S, Stetler-Stevenson M, Kreitman RJ. Soluble CD22 as a tumor marker for hairy cell leukemia. Blood. 2008 Sep 15;112(6):2272-7. doi: 10.1182/blood-2008-01-131987. Epub 2008 Jul 2.

    PMID: 18596230BACKGROUND

  • Kreitman RJ, Margulies I, Stetler-Stevenson M, Wang QC, FitzGerald DJ, Pastan I. Cytotoxic activity of disulfide-stabilized recombinant immunotoxin RFB4(dsFv)-PE38 (BL22) toward fresh malignant cells from patients with B-cell leukemias. Clin Cancer Res. 2000 Apr;6(4):1476-87.

    PMID: 10778980BACKGROUND

  • Robbins DH, Margulies I, Stetler-Stevenson M, Kreitman RJ. Hairy cell leukemia, a B-cell neoplasm that is particularly sensitive to the cytotoxic effect of anti-Tac(Fv)-PE38 (LMB-2). Clin Cancer Res. 2000 Feb;6(2):693-700.

    PMID: 10690555BACKGROUND

  • Kreitman RJ, Wilson WH, White JD, Stetler-Stevenson M, Jaffe ES, Giardina S, Waldmann TA, Pastan I. Phase I trial of recombinant immunotoxin anti-Tac(Fv)-PE38 (LMB-2) in patients with hematologic malignancies. J Clin Oncol. 2000 Apr;18(8):1622-36. doi: 10.1200/JCO.2000.18.8.1622.

    PMID: 10764422RESULT

  • Kreitman RJ, Wilson WH, Robbins D, Margulies I, Stetler-Stevenson M, Waldmann TA, Pastan I. Responses in refractory hairy cell leukemia to a recombinant immunotoxin. Blood. 1999 Nov 15;94(10):3340-8.

    PMID: 10552943RESULT

MeSH Terms

Conditions

LeukemiaLymphomaHodgkin DiseaseLymphoma, T-Cell, CutaneousWaldenstrom MacroglobulinemiaLeukemia, Myeloid, AcutePrecursor Cell Lymphoblastic Leukemia-LymphomaLeukemia, Lymphocytic, Chronic, B-CellLeukemia, Hairy CellLymphoma, FollicularLymphoma, Non-HodgkinLymphoma, Large B-Cell, DiffuseLymphoma, Large-Cell, ImmunoblasticBurkitt LymphomaPrecursor T-Cell Lymphoblastic Leukemia-LymphomaLeukemia, ProlymphocyticLymphoma, Mantle-CellMycosis FungoidesSezary SyndromeLymphoma, B-Cell, Marginal Zone

Interventions

B3(Fv)-PE38KDEL recombinant immunotoxin

Condition Hierarchy (Ancestors)

Neoplasms by Histologic TypeNeoplasmsHematologic DiseasesHemic and Lymphatic DiseasesLymphoproliferative DisordersLymphatic DiseasesImmunoproliferative DisordersImmune System DiseasesLymphoma, T-CellNeoplasms, Plasma CellHemostatic DisordersVascular DiseasesCardiovascular DiseasesParaproteinemiasBlood Protein DisordersHemorrhagic DisordersLeukemia, MyeloidLeukemia, LymphoidLeukemia, B-CellChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and SymptomsLymphoma, B-CellEpstein-Barr Virus InfectionsHerpesviridae InfectionsDNA Virus InfectionsVirus DiseasesInfectionsTumor Virus Infections

Study Officials

  • Robert Kreitman, MD

    National Cancer Institute (NCI)

    STUDY CHAIR

Study Design

Study Type
interventional
Phase
phase 1
Purpose
TREATMENT
Sponsor Type
NIH

Study Record Dates

First Submitted

November 1, 1999

First Posted

May 6, 2003

Study Start

April 1, 1996

Last Updated

April 29, 2015

Record last verified: 2003-03

Locations

US(2)