Moxetumomab Pasudotox for Advanced Hairy Cell Leukemia

NCT ID: NCT01829711

Last Updated: 2020-04-08

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

80 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-04-29

Study Completion Date

2019-04-29

Brief Summary

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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.

Detailed Description

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Background:

* Hairy cell leukemia (HCL) 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 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 intravenously (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.

Conditions

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Leukemia, Hairy Cell

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Moxetumomab pasudotox 40 µg/kg

Patients will receive Moxetumomab Pasudotox intravenously (IV) over 30 minutes on days 1, 3, 5 of each 28 day cycle for a maximum of 6 cycles or until disease progression, unacceptable toxivity, initiation of alternate therapy or documented CR.

Group Type EXPERIMENTAL

Moxetumomab pasudotox

Intervention Type DRUG

IV Bag Protectant for Moxetumomab pasudotox

Intervention Type DRUG

Interventions

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Moxetumomab pasudotox

Intervention Type DRUG

IV Bag Protectant for Moxetumomab pasudotox

Intervention Type DRUG

Eligibility Criteria

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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 rituximab 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 or surface antigen unless the patient is on Lamivudine or Entecavir and Hepatitis B Viral DNA load is less than 2000 IU/mL.
* 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.
* Adequate oxygen saturation
* Radioimmunotherapy within 2 years prior to enrollment in study.
* Adequate hematologic function
* Adequate lung function
* Patients with history of thrombotic microangiopathy or thrombotic microangiopathy / hemolytic uremic syndrome
* Patients with QTc interval (Friderica) 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
Minimum Eligible Age

18 Years

Maximum Eligible Age

100 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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MedImmune LLC

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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MedImmune LLC

Role: STUDY_DIRECTOR

MedImmune LLC

Locations

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Research Site

Duarte, California, United States

Site Status

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Los Angeles, California, United States

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Miami, Florida, United States

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Chicago, Illinois, United States

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Baltimore, Maryland, United States

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Bethesda, Maryland, United States

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Albuquerque, New Mexico, United States

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New York, New York, United States

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Houston, Texas, United States

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Antwerp, , Belgium

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Ghent, , Belgium

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Edmonton, Alberta, Canada

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Brno, , Czechia

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Caen, , France

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Le Chesnay, , France

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Pessac, , France

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Pierre-Bénite, , France

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Rouen, , France

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Strasbourg, , France

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Berlin, , Germany

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Giessen, , Germany

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Heidelberg, , Germany

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Dublin, , Ireland

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Haifa, , Israel

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Bologna, , Italy

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Genova, , Italy

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Milan, , Italy

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Siena, , Italy

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Bergen, , Norway

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Gdansk, , Poland

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Lodz, , Poland

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Belgrade, , Serbia

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Barcelona, , Spain

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Sutton, , United Kingdom

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Countries

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United States Belgium Canada Czechia France Germany Ireland Israel Italy Norway Poland Serbia Spain United Kingdom

References

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Bouroncle BA. Thirty-five years in the progress of hairy cell leukemia. Leuk Lymphoma. 1994;14 Suppl 1:1-12.

Reference Type BACKGROUND
PMID: 7820038 (View on PubMed)

Jemal A, Siegel R, Ward E, Murray T, Xu J, Thun MJ. Cancer statistics, 2007. CA Cancer J Clin. 2007 Jan-Feb;57(1):43-66. doi: 10.3322/canjclin.57.1.43.

Reference Type BACKGROUND
PMID: 17237035 (View on PubMed)

Sharpe RW, Bethel KJ. Hairy cell leukemia: diagnostic pathology. Hematol Oncol Clin North Am. 2006 Oct;20(5):1023-49. doi: 10.1016/j.hoc.2006.06.010.

Reference Type BACKGROUND
PMID: 16990105 (View on PubMed)

Kreitman RJ, Tallman MS, Robak T, Coutre S, Wilson WH, Stetler-Stevenson M, Fitzgerald DJ, Lechleider R, Pastan I. Phase I trial of anti-CD22 recombinant immunotoxin moxetumomab pasudotox (CAT-8015 or HA22) in patients with hairy cell leukemia. J Clin Oncol. 2012 May 20;30(15):1822-8. doi: 10.1200/JCO.2011.38.1756. Epub 2012 Feb 21.

Reference Type BACKGROUND
PMID: 22355053 (View on PubMed)

Kreitman RJ, Dearden C, Zinzani PL, Delgado J, Karlin L, Robak T, Gladstone DE, le Coutre P, Dietrich S, Gotic M, Larratt L, Offner F, Schiller G, Swords R, Bacon L, Bocchia M, Bouabdallah K, Breems DA, Cortelezzi A, Dinner S, Doubek M, Gjertsen BT, Gobbi M, Hellmann A, Lepretre S, Maloisel F, Ravandi F, Rousselot P, Rummel M, Siddiqi T, Tadmor T, Troussard X, Yi CA, Saglio G, Roboz GJ, Balic K, Standifer N, He P, Marshall S, Wilson W, Pastan I, Yao NS, Giles F. Moxetumomab pasudotox in relapsed/refractory hairy cell leukemia. Leukemia. 2018 Aug;32(8):1768-1777. doi: 10.1038/s41375-018-0210-1. Epub 2018 Jul 20.

Reference Type BACKGROUND
PMID: 30030507 (View on PubMed)

Kreitman RJ, Dearden C, Zinzani PL, Delgado J, Robak T, le Coutre PD, Gjertsen BT, Troussard X, Roboz GJ, Karlin L, Gladstone DE, Kuptsova-Clarkson N, Liu S, Patel P, Rotolo F, Mitry E, Pastan I, Giles F; Study 1053 investigators. Moxetumomab pasudotox in heavily pre-treated patients with relapsed/refractory hairy cell leukemia (HCL): long-term follow-up from the pivotal trial. J Hematol Oncol. 2021 Feb 24;14(1):35. doi: 10.1186/s13045-020-01004-y.

Reference Type DERIVED
PMID: 33627164 (View on PubMed)

Abou Dalle I, Ravandi F. Moxetumomab pasudotox for the treatment of relapsed and/or refractory hairy cell leukemia. Expert Rev Hematol. 2019 Sep;12(9):707-714. doi: 10.1080/17474086.2019.1643231. Epub 2019 Aug 1.

Reference Type DERIVED
PMID: 31298972 (View on PubMed)

Provided Documents

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Document Type: Statistical Analysis Plan

View Document

Document Type: Study Protocol

View Document

Related Links

Other Identifiers

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13-C-0106

Identifier Type: OTHER

Identifier Source: secondary_id

CD-ON-CAT-8015-1053

Identifier Type: OTHER

Identifier Source: secondary_id

130106

Identifier Type: -

Identifier Source: org_study_id

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