Moxetumomab Pasudotox for Advanced Hairy Cell Leukemia

Study Description

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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.

Condition or disease	Intervention/treatment	Phase
Leukemia, Hairy Cell	Drug: moxetumomab pasudotox; Drug: IV Bag Protectant for Moxetumomab pasudotox	Phase 3

Detailed Description:

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.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	80 participants
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	A Pivotal Multicenter Trial of Moxetumomab Pasudotox in Relapsed/ Refractory Hairy Cell Leukemia
Actual Study Start Date :	April 29, 2013
Actual Primary Completion Date :	May 24, 2017
Estimated Study Completion Date :	May 30, 2018

Arms and Interventions

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Arm	Intervention/treatment
Experimental: Arm A; Patients will receive Moxetumomab Pasudotox 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

Outcome Measures

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Primary Outcome Measures :

1. Rate of CR in patients treated with study drug [ Time Frame: Every 4 weeks ]

Secondary Outcome Measures :

1. Overall response rate [ Time Frame: every 4 weeks. ]
2. Relapse free survival [ Time Frame: Once patients have a Complete Response (CR), they will be followed with monthly blood work for 6 months then every 3 months for 2 years, then yearly thereafter. Bone marrow examinations at 6 months. ]
3. Progression free survival [ Time Frame: Once patients have a Complete Response (CR), they will be followed with monthly blood work for 6 months then every 3 months for 2 years, then yearly thereafter. Bone marrow examinations at 6 months. ]
4. Time to Response [ Time Frame: Duration of Study ]
   TTR will be measured from start of administartion to the first documentation of response (CR or PR)
5. Safety [ Time Frame: 1st Administration through 30 Days after Last Dose ]
   Occurence of AEs, abnormal laboratory values, and SAEs reported from 1st administration of moxetumomab pasudotox through 30 days after last dose
6. Pharmacokinetic [ Time Frame: Duration of Treatment ]
7. Immunogenic Potential [ Time Frame: Duration of Treatment ]

Eligibility Criteria

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Ages Eligible for Study:	Child, Adult, Senior
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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

Contacts and Locations

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  Show 34 Study Locations

Sponsors and Collaborators

MedImmune LLC

Investigators

Study Director:	MedImmune LLC	MedImmune LLC

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Additional Information:

NIH Clinical Center Detailed Web Page 

Publications:

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

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.

Sharpe RW, Bethel KJ. Hairy cell leukemia: diagnostic pathology. Hematol Oncol Clin North Am. 2006 Oct;20(5):1023-49. Review.

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.

Responsible Party:	MedImmune LLC
ClinicalTrials.gov Identifier:	NCT01829711 History of Changes
Other Study ID Numbers:	130106; 13-C-0106 ( Other Identifier: CTEP ); CD-ON-CAT-8015-1053 ( Other Identifier: MedImmune )
First Posted:	April 11, 2013
Last Update Posted:	February 12, 2018
Last Verified:	February 2018

Studies a U.S. FDA-regulated Drug Product:		Yes
Studies a U.S. FDA-regulated Device Product:		No

Keywords provided by MedImmune LLC:

Moxetumomab Paudotox; CAT-8015; anti-CD22 recombination immunotoxin; Biologic Therapy	Recombinant Immunotoxin; Monoclonal Antibody; Pseudomonas Exotoxin; Targeted Therapy

Additional relevant MeSH terms:

Leukemia; Leukemia, Hairy Cell; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases	Immunoproliferative Disorders; Immune System Diseases; Immunotoxins; Immunologic Factors; Physiological Effects of Drugs