Moxetumomab Pasudotox for Advanced Hairy Cell Leukemia

NCT01829711 | Completed Phase 3 Results DMC FDA Drug

• 3 other identifiers: 13010613-C-0106CD-ON-CAT-8015-1053
• Study Type: interventional
• Target: 80
• Locations: 14 countries
• Sites: 34

Brief 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.

Conditions

Leukemia, Hairy Cell

Keywords

Moxetumomab Pasudotox; CAT-8015; Anti-cd22 recombinant immunotoxin; Biologic Therapy; Monoclonal Antibody; Pseudomonas Exotoxin; Targeted Therapy

Outcome Measures

Primary Outcomes (2)

• Percentage of Participants With Durable Complete Response (CR) Assessed by Blinded Independent Central Review

  Durable CR was defined as overall response that meets blood, bone marrow and imaging criteria for CR, followed by a \>180 day duration of hematologic remission (HR). CR requires all of the following to be present: No evidence of leukemic cells in peripheral blood and/or by routine H/E staining of bone marrow; Resolution of any hepatomegaly, splenomegaly, and abnormal (\>= 2 cm minimum length) lymphadenopathy by CT or MRI (maximum diameter of spleen should be either \< 17 cm or have decreased by \>25% from its baseline.); HR requires normal complete blood count (CBC) as exhibited by: Neutrophils \>= 1.5 x 10\^9/L, Platelets \>= 100 x 10\^9/L, and hemoglobin \>= 11.0 g/dL without transfusions or growth factors for at least 4 weeks.

  Full disease assessment (CBC, bone marrow and imaging) at end of treatment (EOT; up to 24 weeks) and post EOT Day 181; CBC monthly for 6 months post EOT, every 3 months post Day 181 for first 2 years and every 6 months thereafter (approximately 6 years)

• Percentage of Participants With Durable CR by Investigator's Assessment

  Durable CR was defined as overall response that meets blood, bone marrow and imaging criteria for CR, followed by a \>180 day duration of HR. CR requires all of the following to be present: No evidence of leukemic cells in peripheral blood and/or by routine H/E staining of bone marrow; Resolution of any hepatomegaly, splenomegaly, and abnormal (\>= 2 cm minimum length) lymphadenopathy by CT or MRI (maximum diameter of spleen should be either \< 17 cm or have decreased by \>25% from its baseline.); HR requires normal complete blood count (CBC) as exhibited by: Neutrophils \>= 1.5 x 10\^9/L, Platelets \>= 100 x 10\^9/L, and hemoglobin \>= 11.0 g/dL without transfusions or growth factors for at least 4 weeks.

  Full disease assessment (CBC, bone marrow and imaging) at end of treatment (EOT; up to 24 weeks) and post EOT Day 181; CBC monthly for 6 months post EOT, every 3 months post Day 181 for first 2 years and every 6 months thereafter (approximately 6 years)

Secondary Outcomes (26)

• Percentage of Participants With Minimal Residual Disease (MRD) Positive or MRD Negative CR Assessed by Blinded Independent Central Review

  Prior to each treatment cycle, EOT (up to 24 weeks), monthly from the EOT assessment until the Day 181 assessment (only for CBC), at follow-up visits every 3 months for the next 24 months, and every 6 months thereafter (approximately 6 years)

• Percentage of Participants With MRD Positive or MRD Negative CR by Investigator's Assessment

  Prior to each treatment cycle, end of treatment, and at follow-up visits every 3 months for the next 24 months and every 6 months thereafter (Approximately 6 years)

• Time to CR Assessed by Blinded Independent Central Review

  Prior to each treatment cycle, EOT (up to 24 weeks), monthly from the EOT assessment until the Day 181 assessment (only for CBC), at follow-up visits every 3 months for the next 24 months, and every 6 months thereafter (approximately 6 years)

• Duration of CR Assessed by Blinded Independent Central Review

  Prior to each treatment cycle, EOT (up to 24 weeks), monthly from the EOT assessment until the Day 181 assessment (only for CBC), at follow-up visits every 3 months for the next 24 months, and every 6 months thereafter (approximately 6 years)

• Duration of Hematologic Remission

  Prior to each treatment cycle, EOT (up to 24 weeks), monthly from the EOT assessment until the Day 181 assessment (only for CBC), at follow-up visits every 3 months for the next 24 months, and every 6 months thereafter (approximately 6 years)

Study Arms (1)

Moxetumomab pasudotox 40 µg/kg

EXPERIMENTAL

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.

Drug: Moxetumomab pasudotox; Drug: IV Bag Protectant for Moxetumomab pasudotox

Interventions

Moxetumomab pasudotox DRUG

Moxetumomab pasudotox 40 µg/kg

IV Bag Protectant for Moxetumomab pasudotox DRUG

Moxetumomab pasudotox 40 µg/kg

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• MedImmune LLC: lead

Study Sites (34)

Research Site

Duarte, California, 91010, United States

Location

Research Site

Los Angeles, California, 90095, United States

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Miami, Florida, 33136, United States

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Chicago, Illinois, 60611, United States

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Baltimore, Maryland, 21287, United States

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Bethesda, Maryland, 20892, United States

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Albuquerque, New Mexico, 87131, United States

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New York, New York, 10065, United States

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Houston, Texas, 77030, United States

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Antwerp, 2060, Belgium

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Ghent, 9000, Belgium

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Edmonton, Alberta, T6G 2G7, Canada

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Brno, 625 00, Czechia

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Caen, 14033, France

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Le Chesnay, 78157, France

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Pessac, 33604, France

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Pierre-Bénite, 69310, France

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Rouen, 76038, France

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Strasbourg, 67098, France

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Berlin, 13353, Germany

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Giessen, 35392, Germany

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Heidelberg, 69120, Germany

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Dublin, DUBLIN 8, Ireland

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Haifa, 31048, Israel

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Bologna, 40138, Italy

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Genova, 16132, Italy

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Milan, 20122, Italy

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Siena, 53100, Italy

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Bergen, 5099, Norway

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Gdansk, 80-952, Poland

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Lodz, 93-510, Poland

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Belgrade, 11000, Serbia

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Barcelona, 08036, Spain

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Sutton, SM2 5PT, United Kingdom

Location

Related Publications (7)

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

  PMID: 7820038 BACKGROUND

• 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.

  PMID: 17237035 BACKGROUND

• 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.

  PMID: 16990105 BACKGROUND

• 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.

  PMID: 22355053 BACKGROUND

• 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.

  PMID: 30030507 BACKGROUND

• 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.

  PMID: 33627164 DERIVED

• 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.

  PMID: 31298972 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page
• 130106\_(CD-ON-CAT-8015-1053)\_current\_SAP\_redacted\_PDF-A
• Protocol-cd-on-cat-8015-1053-amendment-9\_redacted\_PDF-A

MeSH Terms

Conditions

Leukemia, Hairy Cell

Interventions

immunotoxin HA22

Condition Hierarchy (Ancestors)

Leukemia; 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: Priti Patel
• Organization: MedImmune, LLC

information.center@astrazeneca.com

+1-650-264-9079

Study Officials

• MedImmune LLC

  MedImmune LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 9, 2013
• First Posted: April 11, 2013
• Study Start: April 29, 2013
• Primary Completion: May 24, 2017
• Study Completion: April 29, 2019
• Last Updated: April 8, 2020
• Results First Posted: August 27, 2018

Record last verified: 2020-03

Locations

BE (2); CA (1); IT (4); IL (1); FR (6); SE (1); ES (1); CZ (1); DE (3); IE (1); NO (1); GB (1); PL (2); US (9)