A Phase II Study Of Imtox-25 In Adults With Refractory/Relapsed Cd25 Positive Adult T Cell Leukemia/Lymphoma

NCT01378871 | Terminated Phase 2 Results

• 1 other identifier: 2009-530
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 7

Brief Summary

This clinical trial will be a multicenter phase II fixed-dose trial in which a minimum of 10 patients with immunophenotypically confirmed ATL with at least 50% of the blasts expressing CD25 as measured by flow cytometry at relapse, will receive Imtox-25. Patients are eligible for repeat courses of treatment every two weeks if they do not experience a dose limiting toxicity (DLT) as defined in Section 5.2 and do not have a HAMA/HARA level \> 1 μg/ml. The treatment will be administered in the in-patient setting. If no response is observed among the initial 9 patients, the study would be terminated early and declared negative; if at least one response is observed, accrual would continue to a total of 17 evaluable patients (total study size=19 to account for 10% of the patients being unevaluable for any reason).

Conditions

Adult T Cell Leukemia; Adult T Cell Lymphoma

Keywords

T Cell; T-Cell; Leukemia; Lymphoma; Leukemia/Lymphoma; ATL

Outcome Measures

Primary Outcomes (1)

• Overall Response of Imtox-25

  To determine any anti-tumor activity of Imtox-25 in relapsed/refractory ATL patients within the confines of a Phase II study as defined by overall response

  28 days

Secondary Outcomes (1)

• Toxicity and Affect of Treatment

  28 days +

Study Arms (1)

Antibody Therapy

EXPERIMENTAL

Treatment with Imtox-25 intravenously over 4 hours every other day for 4 doses. Hospital admission is required during this treatment.

Drug: IMTOX-25

Interventions

IMTOX-25 DRUG

This agent is supplied as a sterile solution at 0.5 mg/ml. Thus a vial with 5 mL contains 2.5 mg IMTOX-25 IMTOX-25 is an immunotoxin. It is an antibody that is bound to a piece of the poison ricin. This antibody have been shown to bind to leukemia cells and kill them because of the ricin. 15 mg/m²/cycle IV. The calculated total dose for the cycle will be divided by four and given on Days 1, 3, 5 and 7.

Also known as: RFT5-dgA

Antibody Therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \> 17 years inclusive at the time of original diagnosis of HTLV-1 associated ATL.
• Histologic verification of ATL and HTLV-1 sero-positivity at diagnosis and either evidence of relapse/refractory disease based on a Bone Marrow/Peripheral Blood examination or evidence by flow cytometry.
• Disease refractory to conventional CHOP based therapy or transplantation or deemed ineligible for salvage by transplantation.
• Presence of CD25 on at least 50% of the lymphoblasts obtained via BMA or peripheral blood as determined by flow cytometry.
• ECOG performance status 2.
• Life expectancy of \> 2 months.
• Patients must have recovered from effects of prior therapy. At least 2 weeks should have elapsed since the last dose of chemotherapy (4 weeks in the case of nitrosourea-containing therapy). Steroids are considered as chemotherapy. However, if the patient has recovered from the side effects of prior therapy and has had a \> 50% rise in peripheral blast count, they are immediately eligible. The 50% rise in peripheral blast count must be calculated as follows. The sample for the baseline peripheral blast count must have been taken at least 24 hours after the end of chemotherapy. The sample for the peripheral blast count that is increased by 50% of the baseline peripheral blast count may be taken at any subsequent time. A second peripheral blast count confirming the 50% rise is recommended.
• No hematopoietic limitations as patients with relapsed leukemia routinely have pancytopenia and ITs have not demonstrated hematopoietic toxicity.
• Adequate renal function defined as a serum creatinine 1.5 x normal range.
• Adequate liver function defined as a total bilirubin 1.5 x normal range and SGOT (AST) or SGPT (ALT) 1.5 x normal range.
• Adequate cardiac function defined as a shortening fraction of 27% by echocardiogram, or ejection fraction of 35-40% by MUGA scan.
• Adequate pulmonary function defined as no evidence of dyspnea at rest.
• Normal neurological exam.
• Patient and/or legal guardian must sign a written informed consent.
• All institutional, FDA, and NCI requirements for human studies must be met.

You may not qualify if:

• Presence of leukemic or infectious pulmonary parenchymal disease or presence of a pulmonary effusion by chest x-ray.
• Presence of CNS involvement with leukemia.
• History of documented seizure disorder or abnormal neurological examination.
• Human anti-mouse (HAMA) levels of \< 1 μg/ml.

Sponsors & Collaborators

• Amit Verma: lead

Study Sites (7)

Albert Einstein Cancer Center at Albert Einstein College of Medicine

The Bronx, New York, 10461, United States

Location

Albert Einstein Cancer Center

The Bronx, New York, 10461, United States

Location

Albert Einstein Comprehensive Cancer Center

The Bronx, New York, 10461, United States

Location

Montefiore Medical Center

The Bronx, New York, 10461, United States

Location

Albert Einstein Clinical Cancer Center

The Bronx, New York, 10467, United States

Location

Montefiore Medical Center-

The Bronx, New York, 10467, United States

Location

Montefiore Medical Center

The Bronx, New York, 10467, United States

Location

Related Publications (12)

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  PMID: 16155611 BACKGROUND

• Waldmann TA, Goldman CK, Bongiovanni KF, Sharrow SO, Davey MP, Cease KB, Greenberg SJ, Longo DL. Therapy of patients with human T-cell lymphotrophic virus I-induced adult T-cell leukemia with anti-Tac, a monoclonal antibody to the receptor for interleukin-2. Blood. 1988 Nov;72(5):1805-16.

  PMID: 2846094 BACKGROUND

• Waldmann TA, White JD, Goldman CK, Top L, Grant A, Bamford R, Roessler E, Horak ID, Zaknoen S, Kasten-Sportes C, et al. The interleukin-2 receptor: a target for monoclonal antibody treatment of human T-cell lymphotrophic virus I-induced adult T-cell leukemia. Blood. 1993 Sep 15;82(6):1701-12.

  PMID: 8400227 BACKGROUND

• Gill PS, Harrington W Jr, Kaplan MH, Ribeiro RC, Bennett JM, Liebman HA, Bernstein-Singer M, Espina BM, Cabral L, Allen S, et al. Treatment of adult T-cell leukemia-lymphoma with a combination of interferon alfa and zidovudine. N Engl J Med. 1995 Jun 29;332(26):1744-8. doi: 10.1056/NEJM199506293322603.

  PMID: 7760890 BACKGROUND

• Thrush GR, Lark LR, Clinchy BC, Vitetta ES. Immunotoxins: an update. Annu Rev Immunol. 1996;14:49-71. doi: 10.1146/annurev.immunol.14.1.49.

  PMID: 8717507 BACKGROUND

• Ghetie V, Ghetie MA, Uhr JW, Vitetta ES. Large scale preparation of immunotoxins constructed with the Fab' fragment of IgG1 murine monoclonal antibodies and chemically deglycosylated ricin A chain. J Immunol Methods. 1988 Sep 13;112(2):267-77. doi: 10.1016/0022-1759(88)90367-5.

  PMID: 3262139 BACKGROUND

• Barth S, Schnell R, Diehl V, Engert A. Development of immunotoxins for potential clinical use in Hodgkin's disease. Ann Oncol. 1996;7 Suppl 4:135-41. doi: 10.1093/annonc/7.suppl_4.s135.

  PMID: 8836425 BACKGROUND

• Winkler U, Gottstein C, Schon G, Kapp U, Wolf J, Hansmann ML, Bohlen H, Thorpe P, Diehl V, Engert A. Successful treatment of disseminated human Hodgkin's disease in SCID mice with deglycosylated ricin A-chain immunotoxins. Blood. 1994 Jan 15;83(2):466-75.

  PMID: 8286745 BACKGROUND

• Engert A, Diehl V, Schnell R, Radszuhn A, Hatwig MT, Drillich S, Schon G, Bohlen H, Tesch H, Hansmann ML, Barth S, Schindler J, Ghetie V, Uhr J, Vitetta E. A phase-I study of an anti-CD25 ricin A-chain immunotoxin (RFT5-SMPT-dgA) in patients with refractory Hodgkin's lymphoma. Blood. 1997 Jan 15;89(2):403-10.

  PMID: 9002941 BACKGROUND

• Schnell R, Vitetta E, Schindler J, Borchmann P, Barth S, Ghetie V, Hell K, Drillich S, Diehl V, Engert A. Treatment of refractory Hodgkin's lymphoma patients with an anti-CD25 ricin A-chain immunotoxin. Leukemia. 2000 Jan;14(1):129-35. doi: 10.1038/sj.leu.2401626.

  PMID: 10637488 BACKGROUND

• Martin PJ, Pei J, Gooley T, Anasetti C, Appelbaum FR, Deeg J, Hansen JA, Nash RA, Petersdorf EW, Storb R, Ghetie V, Schindler J, Vitetta ES. Evaluation of a CD25-specific immunotoxin for prevention of graft-versus-host disease after unrelated marrow transplantation. Biol Blood Marrow Transplant. 2004 Aug;10(8):552-60. doi: 10.1016/j.bbmt.2004.04.002.

  PMID: 15282533 BACKGROUND

• Amrolia PJ, Mucioli-Casadei G, Huls H, Heslop HE, Schindler J, Veys P, Vitetta ES, Brenner MK. Add-back of allodepleted donor T cells to improve immune reconstitution after haplo-identical stem cell transplantation. Cytotherapy. 2005;7(2):116-25. doi: 10.1080/14653240510018181.

  PMID: 16047416 BACKGROUND

MeSH Terms

Conditions

Precursor T-Cell Lymphoblastic Leukemia-Lymphoma; Leukemia; Lymphoma

Interventions

RFT5-SMPT-dgA immunotoxin

Condition Hierarchy (Ancestors)

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Results Point of Contact

• Title: Dr, Amit Verma
• Organization: Albert Einstein College of Medicine

amit.verma@einsteinmed.edu

Study Officials

• Samir Parekh, MD

  Montefiore Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor, Oncology

Study Record Dates

• First Submitted: May 12, 2011
• First Posted: June 23, 2011
• Study Start: September 1, 2010
• Primary Completion: January 1, 2013
• Study Completion: January 1, 2013
• Last Updated: June 9, 2023
• Results First Posted: June 9, 2023

Record last verified: 2023-05

Locations

US (7)