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

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Brief Title

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

Official Title

Phase II Study of Therapy With IMTOX-25 in Adults With Refractory/Relapsed Cd25 Positive Adult T Cell Leukemia/Lymphoma

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).
    

Detailed Description

      Adult T Cell Leukemia/Lymphoma (ATL) is a lymphoproliferative disease associated with HTLV-1
      infection, characterized by circulating malignant cells expressing the IL-2 receptor (CD25).
      Prognosis for patients with ATL remains poor despite advances in chemotherapy, with survival
      in leukemic patients ranging from six months to less than one year. Novel agents that are
      potent and specific for the tumor cells are urgently needed to improve overall survival and
      decrease toxicity in this dismal disease. One therapeutic approach would be to use
      immunotoxins (ITs). ITs utilize a potent toxin linked to a targeting moiety designed to
      maximize drug delivery to the tumor cells, thus avoiding the nonspecific toxicity of
      conventional chemotherapeutic agents. Imtox-25 is constructed using the RFT5 murine
      monoclonal antibody (Mab) coupled to deglycosylated ricin-A chain (dgA) via the
      heterobifunctional, thiol-containing crosslinker, 4[(succinimidyloxy)
      carbonyl]-Ą-methyl-Ą-(2 pyridyldithio) toluene (SMPT). Phase I and II clinical studies with
      Imtox-25 (RFT5.dGA) have been shown safety and efficacy in adult patients with Hodgkin¡¦s
      disease and a recommended Phase II dose has been established.. In vitro experiments using ATL
      cell lines and in vivo studies in a murine xenograft model have demonstrated significant
      activity of Imtox-25 in this disease. Based on these results, the investigators propose to
      conduct a phase II trial utilizing Imtox-25 in adults with relapsed or refractory ATL.
    

Study Phase

Phase 2

Study Type

Interventional


Primary Outcome

overall response

Secondary Outcome

 Toxicity and Affect of Treatment

Condition

Adult T Cell Leukemia

Intervention

IMTOX-25

Study Arms / Comparison Groups

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

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

1

Start Date

September 2010

Completion Date

January 2013

Primary Completion Date

January 2013

Eligibility Criteria

        Inclusion Criteria:

          -  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.

        Exclusion Criteria:

          -  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.
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Samir Parekh, MD, , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT01378871

Organization ID

2009-530


Responsible Party

Sponsor-Investigator

Study Sponsor

Amit Verma


Study Sponsor

Samir Parekh, MD, Principal Investigator, Montefiore Medical Center


Verification Date

September 2019