Moxetumomab Pasudotox for Advanced Hairy Cell Leukemia
- 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.
- To see how effective moxetumomab pasudotox is at destroying hairy cell leukemia tumor cells and producing lasting complete remissions.
- Individuals at least 18 years of age who have hairy cell leukemia that has not responded to or relapsed at least twice after standard therapy.
- Participants will be screened with a physical exam and medical history. Blood and urine samples will be collected. Imaging studies and heart and lung function tests will also be performed.
- Participants will have 28-day cycles of treatment. They will receive the study drug on days 1, 3, and 5 of every cycle. Each dose will take about 30 minutes.
- Treatment will be monitored with frequent blood and urine tests and imaging studies.
- The study will focus on the results from the first 6 months of treatment. However, participants will continue to take the study drug for as long as it is effective and the side effects are not severe.
- After stopping the study drug, participants will have frequent follow-up visits to monitor the outcome of the treatment.
Leukemia, Hairy Cell
Drug: moxetumomab pasudotox
Drug: IV Bag Protectant for Moxetumomab pasudotox
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Pivotal Multicenter Trial of Moxetumomab Pasudotox in Relapsed/ Refractory Hairy Cell Leukemia|
- Rate of CR in patients treated with study drug [ Time Frame: Every 4 weeks ] [ Designated as safety issue: No ]
- Overall response rate [ Time Frame: every 4 weeks. ] [ Designated as safety issue: No ]
- 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 every 6 months. Bone marrow examinations at 6 months then yearly for 2 years, then every 2 years. ] [ Designated as safety issue: No ]
- Progression free survival [ Time Frame: Once patients have a Complete Response (CR), Patients will be followed with monthly blood work for 6 months then every 3 months for 2 years, then every 6 months. Bone marrow examinations at 6 months then yearly for 2 years, then every 2 years. ] [ Designated as safety issue: No ]
|Study Start Date:||March 2013|
|Estimated Study Completion Date:||November 2016|
|Estimated Primary Completion Date:||September 2016 (Final data collection date for primary outcome measure)|
Experimental: Arm A
Patients will receive 40mcg/kg Moxetumomab Pasudotox IV over 30 minutes on days 1, 3, 5 of each 28 day cycle until CR, PD, initiation of alternate therapy or unacceptable toxicity. There is no maximum duration of therapy on this protocol.
Drug: moxetumomab pasudotox
N/ADrug: IV Bag Protectant for Moxetumomab pasudotox
Hide Detailed Description
- 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 remission (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
- 114 patients have been treated with moxetumomab pasudotox, including 48 with HCL. Moxetumomab pasudotox was generally well tolerated in HCL patients with no MTD defined and some patients treated for over a year.
- Currently there are no approved agents with significant efficacy for HCL patients after failure of standard therapy
- The primary objective of this study is to determine the rate of durable complete response (CR) in multiply relapsed HCL with moxetumomab pasudotox. To meet the primary endpoint, patients will need to meet standard criteria for CR by analysis of blood, bone marrow and imaging, and maintain a hematologic remission (HR), namely the blood counts needed for CR, for > 180 days.
- Secondary objectives include determining the overall response rate (ORR), progressionfree survival (PFS), time t otreatment failure (TIF), duration of responses (CR and PR), confirming safety, and evaluating immunogenicity and pharmacokinetics.
- Histologically confirmed, immunotoxin-na(SqrRoot) ve hairy cell leukemia with a need for therapy based on at least one of the following criteria:
neutrophils < 1000/mm(3)
platelets < 100,000/mm(3)
hemoglobin < 10 g/dL)
- Have had at least 2 prior systemic therapies, including at least 2 prior courses of purine analog, or 1 if the response to this course lasted < 1 year, or if the patient had unacceptable toxicity to purine analog.
- Age greater than or equal to 18 years
- 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 40 mcg/kg moxetumomab pasudotox IV on days 1, 3 and 5 of each 28 day cycle until the subject progresses, toxicity occurs, the subject begins alternate therapy, or 2 cycles beyond CR (for subjects who have no assessable minimal residual disease). If less than or equal to 2 of the first 25 patients do not achieve durable CR, no additional patients will be accrued
- The primary endpoint is to determine the durable complete response (CR) rate of moxetumomab pasudotox with a minimum duration of > 180 days. A durable CR will be defined as one in which hematologic remission (HR), namely the blood counts required for CR, are maintained for > 180 days from the time CR was first confirmed by tests of marrow, imaging and blood. Recurrent sustained (nontransient) cytopenias, particularly during the first 6 months of CR, will prompt a repeat bone marrow study to confirm relapse. The durable CR rate and its 95% CI will be constructed using the exact probability method (Clopper-Pearson exact interval) in the Intent-to-Treat population. With 77 patients enrolled, there will be 90% power to detect a difference between 28% and 13% (expected CR rate from best alternative non-chemotherapy treatment, rituximab) durable CR rates using 2- sided significance level of 0.05.
The overall IRB accrual ceiling is currently set at 80 to allow for a small number of patients that cannot be assessed for response.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01829711
|Contact: Elizabeth J Maestri, R.N.||(301) email@example.com|
|Contact: Robert J Kreitman, M.D.||(301) firstname.lastname@example.org|
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office 888-624-1937|
|United States, Ohio|
|Ohio State University||Recruiting|
|Columbus, Ohio, United States, 43210-1240|
|United States, Texas|
|MD Anderson Cancer Center||Recruiting|
|Houston, Texas, United States, 77030-4096|
|Principal Investigator:||Robert J Kreitman, M.D.||National Cancer Institute (NCI)|