NCT01829711 · REGISTRY CONDITION SEARCH

Moxetumomab Pasudotox for Advanced Hairy Cell Leukemia

Found through the registry condition index, not selected as a treatment recommendation. This discovery collection was restricted to studies with posted results.

Phase: PHASE3
Status at capture: COMPLETED
Registry last update: 2020-04-08

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

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

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outcome · POSTED

Percentage of Participants With Durable CR by Investigator's Assessment

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outcome · POSTED

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

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outcome · POSTED

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

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outcome · POSTED

Time to CR Assessed by Blinded Independent Central Review

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outcome · POSTED

Duration of CR Assessed by Blinded Independent Central Review

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outcome · POSTED

Duration of Hematologic Remission

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outcome · POSTED

Time to Hematologic Remission

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outcome · POSTED

Percentage of Participants With Objective Response (OR) Assessed by Blinded Independent Central Review

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outcome · POSTED

Percentage of Participants With Objective Response by Investigator's Assessment

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outcome · POSTED

Time to Objective Response Assessed by Blinded Independent Central Review

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outcome · POSTED

Duration of Objective Response Assessed by Blinded Independent Central Review

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outcome · POSTED

Progression-free Survival (PFS) Assessed by Blinded Independent Central Review

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outcome · POSTED

Time to Treatment Failure (TTF) Assessed by Blinded Independent Central Review

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outcome · POSTED

Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)

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outcome · POSTED

Number of Participants With Abnormal Clinical Laboratory Results Reported as TEAEs

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outcome · POSTED

Number of Participants With Abnormal Vital Signs Reported as TEAEs

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outcome · POSTED

Number of Participants With Abnormal Electrocardiogram (ECG) Reported as TEAEs

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outcome · POSTED

Time to Reach Maximum Observed Plasma Concentration (Tmax) of Moxetumomab Pasudotox

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outcome · POSTED

Maximum Observed Plasma Concentration (Cmax) of Moxetumomab Pasudotox

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outcome · POSTED

Time of Last (Tlast) Measurable Concentration of Moxetumomab Pasudotox

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outcome · POSTED

Area Under the Plasma Concentration-time Curve From Time Zero to Time of the Last Quantifiable Concentration (AUC0-last) of Moxetumomab Pasudotox

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outcome · POSTED

Area Under the Plasma Concentration-time Curve From Time Zero to 3 Hours (AUC0-3hr) Post End of Moxetumomab Pasudotox

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outcome · POSTED

Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of Moxetumomab Pasudotox

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outcome · POSTED

Area Under the Plasma Concentration-time Curve Extrapolated (AUCExt) of Moxetumomab Pasudotox

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outcome · POSTED

Systemic Clearance (CL) of Moxetumomab Pasudotox

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outcome · POSTED

Terminal Half Life (t1/2) of Moxetumomab Pasudotox

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outcome · POSTED

Percentage of Participants With Positive Anti-drug Antibodies (ADA), Neutralizing Anti-drug Antibodies (nAb) and Specificity (CD22 and PE38) Positive to Moxetumomab Pasudotox

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

eligibility 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 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
healthy Volunteers: false
maximum Age: 100 Years
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
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.
intervention Names
Drug: Moxetumomab pasudotox
Drug: IV Bag Protectant for Moxetumomab pasudotox
label
Moxetumomab pasudotox 40 µg/kg
type
EXPERIMENTAL

interventions

arm Group Labels
Moxetumomab pasudotox 40 µg/kg
name
Moxetumomab pasudotox
type
DRUG
arm Group Labels
Moxetumomab pasudotox 40 µg/kg
name
IV Bag Protectant for Moxetumomab pasudotox
type
DRUG

Study design

allocation

intervention Model

SINGLE_GROUP

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 80
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
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.
measure
Percentage of Participants With Durable Complete Response (CR) Assessed by Blinded Independent Central Review
time Frame
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)
description
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.
measure
Percentage of Participants With Durable CR by Investigator's Assessment
time Frame
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

description
The MRD status by blinded independent review refers specifically to results of central pathologist read of bone marrow biopsy by immunohistochemistry. The CR with Positive or Negative MRD requires all of the following to be present: * No evidence of leukemic cells in the peripheral blood and/or by routine H/E staining of bone marrow. Minimal Residual Disease: CR with HCL evident in blood or in bone marrow biopsy by immunohistochemistry. * Resolution of any hepatomegaly, splenomegaly, and abnormal (\>= 2 cm minimum length) lymphadenopathy by CT or MRI. Although a normal spleen size is not defined, the maximum diameter of the spleen should be either \< 17 cm or have decreased by \>25% from its baseline. * Normal 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.
measure
Percentage of Participants With Minimal Residual Disease (MRD) Positive or MRD Negative CR Assessed by Blinded Independent Central Review
time Frame
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)
description
The MRD status by investigator refers to results of investigator assessment of bone marrow biopsy or bone marrow aspirate by immunohistochemistry and/or flow cytometry. The CR with Positive or Negative MRD requires all of the following to be present: * No evidence of leukemic cells in the peripheral blood and/or by routine H/E staining of bone marrow. Minimal Residual Disease: CR with HCL evident in blood or marrow by flow cytometry. * Resolution of any hepatomegaly, splenomegaly, and abnormal (\>= 2 cm minimum length) lymphadenopathy by CT or MRI. Although a normal spleen size is not defined, the maximum diameter of the spleen should be either \< 17 cm or have decreased by \>25% from its baseline. * Normal 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.
measure
Percentage of Participants With MRD Positive or MRD Negative CR by Investigator's Assessment
time Frame
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)
description
Time to CR was defined as the time from the start of moxetumomab pasudotox administration to the first documentation of CR.
measure
Time to CR Assessed by Blinded Independent Central Review
time Frame
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)
description
Duration of CR was defined as the duration from documentation of CR to the time of relapse from CR. Relapse from CR was defined as any CR criteria (blood counts, imaging or bone marrow) no longer consistent with CR. 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); normal 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.
measure
Duration of CR Assessed by Blinded Independent Central Review
time Frame
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)
description
Duration of HR was defined as the duration from documentation of HR to the time of relapse. HR was defined as the blood counts required for CR as normal 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. Duration of HR was censored on the date of the last hematologic assessment for participants who have no documented relapse based on blood count prior to data cutoff, dropout, or initiation of alternative anticancer therapy.
measure
Duration of Hematologic Remission
time Frame
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)
description
Time to HR was defined as the time from the start of moxetumomab pasudotox administration to the first documentation of HR. HR was defined as the blood counts required for CR as normal 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.
measure
Time to Hematologic Remission
time Frame
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)
description
The OR was defined as number of participants with a best response of CR or PR. CR requires all of 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); normal CBC (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. PR requires all of following for a period of at least 4 weeks: \>=50% decrease or normalization (\<5.0 x 10\^9/L) in peripheral blood lymphocyte count and \>=50% reduction in lymphadenopathy and in abnormal haepatosplenomegaly by CT or MRI from pre-treatment baseline value; normal CBC as mentioned above or 50% improvement in CBC values over baseline without transfusions or growth factors for at least 4 weeks.
measure
Percentage of Participants With Objective Response (OR) Assessed by Blinded Independent Central Review
time Frame
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)
description
The OR was defined as number of participants with a best response of CR or PR. CR requires all of 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); normal CBC (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. PR requires all of following for a period of at least 4 weeks: \>=50% decrease or normalization (\<5.0 x 10\^9/L) in peripheral blood lymphocyte count and \>=50% reduction in lymphadenopathy and in abnormal haepatosplenomegaly by CT or MRI from pre-treatment baseline value; normal CBC as mentioned above or 50% improvement in CBC values over baseline without transfusions or growth factors for at least 4 weeks.
measure
Percentage of Participants With Objective Response by Investigator's Assessment
time Frame
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)
description
Time to OR was defined as the time from the start of moxetumomab pasudotox administration to the first documentation of OR (CR or PR).
measure
Time to Objective Response Assessed by Blinded Independent Central Review
time Frame
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)
description
Duration of OR was defined as the time from the first documentation of objective response (CR or PR) to the date of relapse. Duration of OR was censored on the date of last disease assessment or hematologic assessment for participants who have no documented relapse prior to data cut-off, dropout, or the initiation of alternative anticancer therapy.
measure
Duration of Objective Response Assessed by Blinded Independent Central Review
time Frame
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)
description
The PFS was defined as the time from the start of moxetumomab pasudotox administration to the earliest date of a disease assessment showing a progressive disease/relapse, earliest date of hematologic relapse or date of death, whichever was earlier. The PFS was censored on the date of last disease assessment or hematologic assessment for participants who are alive with no documented relapse or PD prior to data cut-off, dropout, or the initiation of alternative anticancer therapy.
measure
Progression-free Survival (PFS) Assessed by Blinded Independent Central Review
time Frame
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)
description
The TTF was defined as the time from the start of moxetumomab pasudotox administration to the date of the first of relapse, progressive disease, initiation of alternative anticancer therapy, or death due to disease or disease-related complication. The TTF was censored on the date of last disease assessment or hematologic assessment for participants who are alive with no documented relapse or PD prior to data cut-off, dropout, or the initiation of alternative anticancer therapy and also censored for death not accompanied by relapse.
measure
Time to Treatment Failure (TTF) Assessed by Blinded Independent Central Review
time Frame
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)

Full study description

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.
detailed Description: 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.

Source references

references

citation
Bouroncle BA. Thirty-five years in the progress of hairy cell leukemia. Leuk Lymphoma. 1994;14 Suppl 1:1-12.
pmid
7820038
type
BACKGROUND
citation
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
type
BACKGROUND
citation
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
type
BACKGROUND
citation
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
type
BACKGROUND
citation
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
type
BACKGROUND
citation
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
type
DERIVED
citation
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
type
DERIVED