Moxetumomab Pasudotox for Advanced Hairy Cell Leukemia

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2013 by National Institutes of Health Clinical Center (CC)
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
ClinicalTrials.gov Identifier:
NCT01829711
First received: April 9, 2013
Last updated: March 26, 2014
Last verified: October 2013
  Purpose

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.

Objectives:

- To see how effective moxetumomab pasudotox is at destroying hairy cell leukemia tumor cells and producing lasting complete remissions.

Eligibility:

- 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.

Design:

  • 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.

Condition Intervention Phase
Leukemia, Hairy Cell
Drug: moxetumomab pasudotox
Drug: IV Bag Protectant for Moxetumomab pasudotox
Phase 3

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • Rate of CR in patients treated with study drug [ Time Frame: Every 4 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 80
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)
Arms Assigned Interventions
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/A
Drug: IV Bag Protectant for Moxetumomab pasudotox
N/A

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:
  • Patients must have histologically confirmed hairy cell leukemia with a need for therapy based on at least one of the following criteria:

neutrophils less than 1000/mm(3)

platelets less than 100,000/mm(3)

hemoglobin less than 10 g/dL)

symptomatic splenomegaly.

  • Patients must be Pseudomonas-immunotoxin na(SqrRoot) ve
  • Patients must 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 less than 1 year, or if the patient had unacceptable toxicity to purine analog.
  • Men or women age greater than or equal to 18 years. Because this disease does not generally occur in children, children are excluded from this study, but will be eligible for future pediatric trials in other indications.
  • ECOG performance status less than or equal to 2.
  • The effects of moxetumomab pasudotox on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation, and 4 months after completion of moxetumomab pasudotox administration. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
  • Patients must have adequate organ function as defined below:
  • total bilirubin less than or equal to 1.5 mg/dL, unless consistent with Gilbert s (ratio between total and direct bilirubin greater than 5)
  • AST and ALT less than or equal to 3 times upper limit of normal (ULN)
  • alkaline phosphatase less than or equal to 2.5 ULN
  • serum creatinine less than or equal to 1.5 mg/dL or creatinine clearance greater than or equal to 60 mL/min as estimated by the Cockcroft-Gault equation
  • Prothrombin time/INR or partial thromboplastin time less 2.5 ULN, fibrinogen greater than or equal to 0.5 LLN; if on warfarin, INR less than 3.5, if on any other anticoagulation, PT less than 2.5 times baseline
  • Ability to understand and the willingness to sign a written informed consent document.
  • Life expectancy greater than or equal to 6 months

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 because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
  • Patients with clinically significant eye findings during screening
  • Pregnant or breastfeeding females. The effects of moxetumomab pasudotox on the developing fetus are unknown. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with moxetumomab pasudotox breastfeeding should be discontinued if the mother is treated with moxetumomab pasudotox
  • Positive for Hepatitis B 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 dquamous skin cancers
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, malaria infection or psychiatric illness/social situations that would limit compliance with study requirements.
  • HIV-positive patients unless taking appropriate anti-HIV medications with a CD4 count of greater than 200. Otherwise, there may be increased risk of lethal infections when temporarily suppressing normal B-cells.
  • History of allogeneic bone marrow transplant
  • Patients with history of both thromboembolism and known congenital hypercoagulable conditions
  • Uncontrolled pulmonary infection, pulmonary edema
  • Oxygen saturation at rest less than 88% measured by pulse oximetry or PaO (2) less than or equal to 55 mm Hg
  • Serum albumin less than 2 g/dL
  • Radioimmunotherapy within 2 years prior to enrollment in study
  • ANC less than 1000/mm(3), or platelet count less than 50,000/mm(3), if these cytopenias are not judged by the investigator to be due to underlying disease (ie, potentially reversible with antineoplastic therapy). A patient will not be excluded because of pancytopenia greater than or equal to Grade 3, or erythropoietin dependence, if it is due to disease, based on the results of bone marrow studies
  • Patients with less than 50% of predicted forced expiratory volume (FEV1) or less than 50% of predicted diffusing capacity for carbon monoxide (DLCO), corrected for hemoglobin concentration and alveolar volume. Note: Patients with no prior history of pulmonary illness are not required to have PFTs. FEV1 will be assessed after bronchodilator therapy.
  • Patients with history of thrombotic microangiopathy or TTP-HUS.
  • Patients with QTc elevation > grade 1
  • Patient on high dose estrogen
  • Patients with clinical evidence of disseminated intravascular coagulation

Inclusion of Women and Minorities:

Both men and women of all races and ethnic groups are eligible for this trial. No clinically important sex/gender and/or race ethnicity differences are expected from the intervention effect

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01829711

Contacts
Contact: Elizabeth J Maestri, R.N. (301) 402-5633 maestrie@mail.nih.gov
Contact: Robert J Kreitman, M.D. (301) 648-7375 kreitmar@mail.nih.gov

Locations
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
Sponsors and Collaborators
Investigators
Principal Investigator: Robert J Kreitman, M.D. National Cancer Institute (NCI)
  More Information

Additional Information:
Publications:
Responsible Party: National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
ClinicalTrials.gov Identifier: NCT01829711     History of Changes
Other Study ID Numbers: 130106, 13-C-0106
Study First Received: April 9, 2013
Last Updated: March 26, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
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
Protective Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 20, 2014