Moxetumomab Pasudotox for Advanced Hairy Cell Leukemia

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Basic Trial Information

PhaseTypeAgeTrial IDs
Phase IIIBiomarker/Laboratory analysis, Treatment18 and over130106
NCI-2015-01075, 13-C-0106, CD-ON-CAT-8015-1053, NCI-2013-00850, NCT01829711

Trial Description

Summary

Background:

Moxetumomab pasudotox is an experimental non-chemotherapy cancer treatment drug. It

targets CD22, a molecule on the surface of essentially all hairy cell leukemia cells.

Moxetumomab pasudotox binds to CD22, goes into the cell, and releases a toxin which kills

the cell. In a phase I trial it had activity in relapsed/refractory hairy cell leukemia with

safety profile supporting further clinical study (http://ncbi.nlm.nih.gov/pubmed/22355053).

This is a phase III multicenter trial designed to confirm these results.

Further Study Information

Background:

Hairy cell leukemia is an indolent B-cell leukemia comprising 2% of all leukemias, or

approximately 900 of the 44,000 new cases of leukemia/year in the US

Over the last two decades, immunotoxin research has accumulated to support a role for

CD22-targeted therapy in the treatment of HCL.

Moxetumomab pasudotox is a recombinant immunotoxin containing an Fv fragment of an

anti-CD22 monoclonal antibody and truncated Pseudomonas exotoxin.

Moxetumomab pasudotox has demonstrated a high complete response (CR) rate in patients

with chemoresistant hairy cell leukemia (HCL) and has shown activity in pediatric acute

lymphoblastic leukemia as well.

Modification of the structure of moxetumomab pasudotox has greatly improved binding and

cytotoxicity toward CD22 expressing malignant cells compared to the precursor molecule.

Preclinical and clinical studies have demonstrated that this increase in binding

affinity results in improved antitumor activity and tolerability

Currently there are no approved agents with significant efficacy for HCL patients after

failure of standard therapy

Design:

This is a multicenter, single-arm study of moxetumomab pasudotox in patients with

relapsed/refractory hairy cell leukemia.

77 patients will be enrolled to receive moxetumomab pasudotox IV on days 1, 3 and 5 of

each 28 day cycle for a maximum of 6 cycles or until disease progression, unacceptable

toxicity occurs, the subject begins alternate therapy, or documented CR (for subjects

who have no assessable minimal residual disease and not to exceed 6 cycles). If less

than or equal to 2 of the first 25 patients do not achieve durable CR, no additional

patients will be accrued.

The overall IRB accrual ceiling is currently set at 80 to allow for a small number of

patients that cannot be assessed for response.

Eligibility Criteria

Inclusion Criteria:

INCLUSION CRITERIA:

Patients must have histologically confirmed hairy cell leukemia or hairy cell

leukemia variant .with a need for therapy

Patients must be Pseudomonas-immunotoxin naive

Patients must have had at least 2 prior purine analogs, or at least 1 course of

purine analog and 1 of either rituximub or BRAF inhibitor.

Men or women age greater than or equal to 18 years.

ECOG performance status less than or equal to 2.

Patients must have adequate organ function

EXCLUSION CRITERIA

Patients who have had chemotherapy, immunotherapy or radiotherapy within 4 weeks

prior to entering the study.

Patients who are receiving any other investigational agents.

Patients with known brain metastases should be excluded from this clinical trial

Patients with clinically significant ophthalmologic findings during screening

Pregnant or breastfeeding females.

Positive for Hepatitis B core antibody surface antigen unless the patient is on

Lamivudine or Entecavir and Hepatitis B Viral DNA load is less than 2000 IU/mL.

Lymph nodes greater than 4cm or prior splenectomy

Active second malignancy requiring treatment other than minor resection of indolent

cancers like basal cell and squamous skin cancers

HIV-positive patients unless taking appropriate anti-HIV medications with a CD4 count

of greater than 200.

History of allogeneic bone marrow transplant.

Patients with history of both thromboembolism and known congenital hypercoagulable

conditions.

Uncontrolled pulmonary infection, pulmonary edema.

Aequate oxygen saturation

Radioimmunotherapy within 2 years prior to enrollment in study.

Adequate hematologic function

Adequate lung function

Patients with history of thrombotic microangiopathy or TTP-HUS.

Patients with QTc interval (Federica) elevation > 500 msec based on at least 2

separate 12-lead ECGs

Patient on high dose estrogen

Patients with clinical evidence of disseminated intravascular coagulation

Exclusion Criteria:

INCLUSION CRITERIA:

Patients must have histologically confirmed hairy cell leukemia or hairy cell

leukemia variant .with a need for therapy

Patients must be Pseudomonas-immunotoxin naive

Patients must have had at least 2 prior purine analogs, or at least 1 course of

purine analog and 1 of either rituximub or BRAF inhibitor.

Men or women age greater than or equal to 18 years.

ECOG performance status less than or equal to 2.

Patients must have adequate organ function

EXCLUSION CRITERIA

Patients who have had chemotherapy, immunotherapy or radiotherapy within 4 weeks

prior to entering the study.

Patients who are receiving any other investigational agents.

Patients with known brain metastases should be excluded from this clinical trial

Patients with clinically significant ophthalmologic findings during screening

Pregnant or breastfeeding females.

Positive for Hepatitis B core antibody surface antigen unless the patient is on

Lamivudine or Entecavir and Hepatitis B Viral DNA load is less than 2000 IU/mL.

Lymph nodes greater than 4cm or prior splenectomy

Active second malignancy requiring treatment other than minor resection of indolent

cancers like basal cell and squamous skin cancers

HIV-positive patients unless taking appropriate anti-HIV medications with a CD4 count

of greater than 200.

History of allogeneic bone marrow transplant.

Patients with history of both thromboembolism and known congenital hypercoagulable

conditions.

Uncontrolled pulmonary infection, pulmonary edema.

Aequate oxygen saturation

Radioimmunotherapy within 2 years prior to enrollment in study.

Adequate hematologic function

Adequate lung function

Patients with history of thrombotic microangiopathy or TTP-HUS.

Patients with QTc interval (Federica) elevation > 500 msec based on at least 2

separate 12-lead ECGs

Patient on high dose estrogen

Patients with clinical evidence of disseminated intravascular coagulation

Trial Contact Information

Trial Lead Organizations / Sponsors / Collaborators

MedImmune Inc

    Trial Sites

    U.S.A.

    Maryland
    Baltimore

    Johns Hopkins University/Sidney Kimmel Cancer Center

    Douglas Edward Gladstone
    Principal Investigator

    Bethesda

    Mark O Hatfield-Warren Grant Magnuson Clinical Center

    Robert J. Kreitman
    Ph: 301-648-7375

    Robert J. Kreitman
    Principal Investigator

    Link to the current ClinicalTrials.gov record.
    NLM Identifer NCT01829711

    Note: Information about participating sites on pharmaceutical industry trials may be incomplete. Please visit the ClinicalTrials.gov record via the link above for more information about participating sites.