A phase I study of a combination of anti-CD19 and anti-CD22 immunotoxins (Combotox) in adult patients with refractory B-lineage acute lymphoblastic leukaemia

John Schindler, Srikanth Gajavelli, Farhad Ravandi, Yumin Shen, Samir Parekh, Ira Braunchweig, Stefan Barta, Victor Ghetie, Ellen Vitetta, Amit K. Verma

Research output: Contribution to journalArticle

66 Citations (Scopus)

Abstract

Novel agents are needed for patients with refractory and relapsed acute lymphoblastic leukaemia (ALL). Combotox is a 1:1 mixture of two immunotoxins (ITs), prepared by coupling deglycosylated ricin A chain (dgRTA) to monoclonal antibodies directed against CD22 (RFB4-dgRTA) and CD19 (HD37-dgRTA). Pre-clinical data demonstrated that Combotox was effective in killing both pre-B-ALL cell lines and cells from patients with pre-B ALL. A clinical study of paediatric patients in which 3 of 17 patients with ALL experienced complete remission, supported the preclinical work and motivated this study. This study was a Phase I, dose-escalation trial using Combotox in adults with refractory or relapsed B-lineage-ALL. A cycle consisted of three doses, with one dose given every other day. Dose levels were 3, 5, 6, 7 and 8mg/m2 per dose. Seventeen patients, aged 19-72years, were enrolled in this multi-institution study. The maximum tolerated dose was 7mg/m2/dose (21mg/m2/cycle) and vascular leak syndrome was the dose-limiting toxicity. Two patients developed reversible grade 3 elevations in liver function tests. One patient achieved partial remission and proceeded to allogeneic stem cell transplantation. All patients with peripheral blasts experienced decreased blast counts following the administration of Combotox. Thus, Combotox can be safely administered to adults with refractory leukaemia.

Original languageEnglish (US)
Pages (from-to)471-476
Number of pages6
JournalBritish Journal of Haematology
Volume154
Issue number4
DOIs
StatePublished - Aug 2011

Fingerprint

Immunotoxins
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Ricin
Maximum Tolerated Dose
Liver Function Tests
Stem Cell Transplantation
Proxy
combotox
Blood Vessels
Leukemia
Monoclonal Antibodies
Pediatrics
Cell Line

Keywords

  • Anti-CD19
  • Anti-CD22
  • Combotox
  • Immunotoxins
  • Leukaemia

ASJC Scopus subject areas

  • Hematology

Cite this

A phase I study of a combination of anti-CD19 and anti-CD22 immunotoxins (Combotox) in adult patients with refractory B-lineage acute lymphoblastic leukaemia. / Schindler, John; Gajavelli, Srikanth; Ravandi, Farhad; Shen, Yumin; Parekh, Samir; Braunchweig, Ira; Barta, Stefan; Ghetie, Victor; Vitetta, Ellen; Verma, Amit K.

In: British Journal of Haematology, Vol. 154, No. 4, 08.2011, p. 471-476.

Research output: Contribution to journalArticle

Schindler, John ; Gajavelli, Srikanth ; Ravandi, Farhad ; Shen, Yumin ; Parekh, Samir ; Braunchweig, Ira ; Barta, Stefan ; Ghetie, Victor ; Vitetta, Ellen ; Verma, Amit K. / A phase I study of a combination of anti-CD19 and anti-CD22 immunotoxins (Combotox) in adult patients with refractory B-lineage acute lymphoblastic leukaemia. In: British Journal of Haematology. 2011 ; Vol. 154, No. 4. pp. 471-476.
@article{979278bde5d545699bd98947f7feb0f5,
title = "A phase I study of a combination of anti-CD19 and anti-CD22 immunotoxins (Combotox) in adult patients with refractory B-lineage acute lymphoblastic leukaemia",
abstract = "Novel agents are needed for patients with refractory and relapsed acute lymphoblastic leukaemia (ALL). Combotox is a 1:1 mixture of two immunotoxins (ITs), prepared by coupling deglycosylated ricin A chain (dgRTA) to monoclonal antibodies directed against CD22 (RFB4-dgRTA) and CD19 (HD37-dgRTA). Pre-clinical data demonstrated that Combotox was effective in killing both pre-B-ALL cell lines and cells from patients with pre-B ALL. A clinical study of paediatric patients in which 3 of 17 patients with ALL experienced complete remission, supported the preclinical work and motivated this study. This study was a Phase I, dose-escalation trial using Combotox in adults with refractory or relapsed B-lineage-ALL. A cycle consisted of three doses, with one dose given every other day. Dose levels were 3, 5, 6, 7 and 8mg/m2 per dose. Seventeen patients, aged 19-72years, were enrolled in this multi-institution study. The maximum tolerated dose was 7mg/m2/dose (21mg/m2/cycle) and vascular leak syndrome was the dose-limiting toxicity. Two patients developed reversible grade 3 elevations in liver function tests. One patient achieved partial remission and proceeded to allogeneic stem cell transplantation. All patients with peripheral blasts experienced decreased blast counts following the administration of Combotox. Thus, Combotox can be safely administered to adults with refractory leukaemia.",
keywords = "Anti-CD19, Anti-CD22, Combotox, Immunotoxins, Leukaemia",
author = "John Schindler and Srikanth Gajavelli and Farhad Ravandi and Yumin Shen and Samir Parekh and Ira Braunchweig and Stefan Barta and Victor Ghetie and Ellen Vitetta and Verma, {Amit K.}",
year = "2011",
month = "8",
doi = "10.1111/j.1365-2141.2011.08762.x",
language = "English (US)",
volume = "154",
pages = "471--476",
journal = "British Journal of Haematology",
issn = "0007-1048",
publisher = "Wiley-Blackwell",
number = "4",

}

TY - JOUR

T1 - A phase I study of a combination of anti-CD19 and anti-CD22 immunotoxins (Combotox) in adult patients with refractory B-lineage acute lymphoblastic leukaemia

AU - Schindler, John

AU - Gajavelli, Srikanth

AU - Ravandi, Farhad

AU - Shen, Yumin

AU - Parekh, Samir

AU - Braunchweig, Ira

AU - Barta, Stefan

AU - Ghetie, Victor

AU - Vitetta, Ellen

AU - Verma, Amit K.

PY - 2011/8

Y1 - 2011/8

N2 - Novel agents are needed for patients with refractory and relapsed acute lymphoblastic leukaemia (ALL). Combotox is a 1:1 mixture of two immunotoxins (ITs), prepared by coupling deglycosylated ricin A chain (dgRTA) to monoclonal antibodies directed against CD22 (RFB4-dgRTA) and CD19 (HD37-dgRTA). Pre-clinical data demonstrated that Combotox was effective in killing both pre-B-ALL cell lines and cells from patients with pre-B ALL. A clinical study of paediatric patients in which 3 of 17 patients with ALL experienced complete remission, supported the preclinical work and motivated this study. This study was a Phase I, dose-escalation trial using Combotox in adults with refractory or relapsed B-lineage-ALL. A cycle consisted of three doses, with one dose given every other day. Dose levels were 3, 5, 6, 7 and 8mg/m2 per dose. Seventeen patients, aged 19-72years, were enrolled in this multi-institution study. The maximum tolerated dose was 7mg/m2/dose (21mg/m2/cycle) and vascular leak syndrome was the dose-limiting toxicity. Two patients developed reversible grade 3 elevations in liver function tests. One patient achieved partial remission and proceeded to allogeneic stem cell transplantation. All patients with peripheral blasts experienced decreased blast counts following the administration of Combotox. Thus, Combotox can be safely administered to adults with refractory leukaemia.

AB - Novel agents are needed for patients with refractory and relapsed acute lymphoblastic leukaemia (ALL). Combotox is a 1:1 mixture of two immunotoxins (ITs), prepared by coupling deglycosylated ricin A chain (dgRTA) to monoclonal antibodies directed against CD22 (RFB4-dgRTA) and CD19 (HD37-dgRTA). Pre-clinical data demonstrated that Combotox was effective in killing both pre-B-ALL cell lines and cells from patients with pre-B ALL. A clinical study of paediatric patients in which 3 of 17 patients with ALL experienced complete remission, supported the preclinical work and motivated this study. This study was a Phase I, dose-escalation trial using Combotox in adults with refractory or relapsed B-lineage-ALL. A cycle consisted of three doses, with one dose given every other day. Dose levels were 3, 5, 6, 7 and 8mg/m2 per dose. Seventeen patients, aged 19-72years, were enrolled in this multi-institution study. The maximum tolerated dose was 7mg/m2/dose (21mg/m2/cycle) and vascular leak syndrome was the dose-limiting toxicity. Two patients developed reversible grade 3 elevations in liver function tests. One patient achieved partial remission and proceeded to allogeneic stem cell transplantation. All patients with peripheral blasts experienced decreased blast counts following the administration of Combotox. Thus, Combotox can be safely administered to adults with refractory leukaemia.

KW - Anti-CD19

KW - Anti-CD22

KW - Combotox

KW - Immunotoxins

KW - Leukaemia

UR - http://www.scopus.com/inward/record.url?scp=79960843919&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79960843919&partnerID=8YFLogxK

U2 - 10.1111/j.1365-2141.2011.08762.x

DO - 10.1111/j.1365-2141.2011.08762.x

M3 - Article

C2 - 21732928

AN - SCOPUS:79960843919

VL - 154

SP - 471

EP - 476

JO - British Journal of Haematology

JF - British Journal of Haematology

SN - 0007-1048

IS - 4

ER -