Neoplasms

Blood and Lymph Conditions

All Conditions

Immune System Diseases

Rare Diseases

Leukemia

Leukemia, Hairy Cell

Neoplasms by Histologic Type

Hematologic Diseases

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Hairy Cell Leukemia

Antineoplastic Agents

All Drugs and Chemicals

Obinutuzumab

Vemurafenib

Antineoplastic Agents, Immunological

Protein Kinase Inhibitors

Enzyme Inhibitors

Participants with HCL with no prior treatment for the disease

Eligible patients will receive vemurafenib at a dose of 960mg orally twice daily (b.i.d.) continuously in cycles of 4 weeks (28 days) for a total of 4 cycles. In case of certain defined toxicities, dose reductions of vemurafenib by 50% (480mg b.i.d.) or interruptions of up to 15 days are permitted. If additional dose reduction is required, vemurafenib may be reduced to 240mg oral b.i.d.

Obinutuzumab will be administered concomitantly with vemurafenib starting at cycle 2 of treatment in cycles of 4 weeks. Obinutuzumab infusions will be administered at 1000mg per day on days 1, 8 and 15 during the cycle 2 and 1000mg per day every 4 weeks during the cycle 3 and 4 of treatment.

Jae Park, MD

This is a multi-center, open label, single arm, phase II trial of the oral BRAF inhibitor, vemurafenib, plus obinutuzumab in patients with previously untreated HCL. A Simon mini-max two-stage design will be employed to assess the efficacy of the combination treatment of vemurafenib and obinutuzumab. In the first stage of the protocol, 9 patients will be treated. If fewer than 6 CRs are seen among the first 9 patients, the study will be closed for lack of efficacy. If at least 7 patients respond to the treatment, then an additional 19 patients will be accrued to the second stage, for a total of 28 patients.

Eligible patients will receive vemurafenib at a dose of 960mg orally twice daily (b.i.d.) continuously in cycles of 4 weeks (28 days) for a total of 4 cycles.

Obinutuzumab will be administered concomitantly with vemurafenib starting at cycle 2 of treatment in cycles of 4 weeks. Obinutuzumab infusions will be administered at 1000mg per day on days 1, 8 and 15 during the cycle 2 and 1000mg per day every 4 weeks during the cycle 3 and 4 of treatment. After the completion of the treatment (i.e. after 4 cycles), a bone marrow aspirate and biopsy will be performed for assessment of response and evaluation of minimal residual disease (MRD). In case of certain defined toxicities, dose reductions of vemurafenib by 50% (480mg b.i.d.) or interruptions of up to 15 days are permitted. If additional dose reduction is required, vemurafenib may be reduced to 240mg oral b.i.d.

A Phase II Study of the BRAF Inhibitor, Vemurafenib, Plus Obinutuzumab in Patients With Previously Untreated Classical Hairy Cell Leukemia

Efficacy as assessed by complete response (CR) rates of participants

Dana-Farber Cancer Institute

Yale University

Memorial Sloan Kettering Cancer Center

Symptoms and General Pathology

Behaviors and Mental Disorders

Skin and Connective Tissue Diseases

Syndrome

Lymphoma

Hematologic Neoplasms

Mastocytosis

Leukemia, Myeloid

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Hodgkin Disease

Preleukemia

Myelodysplastic Syndromes

Aggression

Leukemia, B-Cell

Leukemia, Myeloid, Acute

Mastocytosis, Systemic

Bone Marrow Diseases

Myeloproliferative Disorders

Chronic Disease

Disease Attributes

Neoplasms, Connective Tissue

Neoplasms, Connective and Soft Tissue

Mast Cell Activation Disorders

Leukemia, Lymphoid

Myeloid Leukemia

Lymphosarcoma

Chronic Graft Versus Host Disease

Chronic Myeloid Leukemia

Hodgkin Lymphoma

Acute Graft Versus Host Disease

Dendritic Cell Tumor

Blastic Plasmacytoid Dendritic Cell

Chronic Myeloproliferative Disorders

Escalating doses of MGD024 will be assigned based on safety and tolerability of the previous dose level.

MGD024 is a CD123 x CD3 bispecific DART® molecule designed to target CD123-expressing leukemic cells for elimination by CD3-expressing T lymphocytes.

MGD024

Global Trial Manager

Eric Winer, MD

Morgan Johnson

Ashley Ward, M.D.

CP-MGD024-01 is a Phase 1, open-label, multi-center study of MGD024 as a single agent in patients with select blood cancers that have not responded to treatment with standard therapies or who have relapsed after treatment. The study is designed to determine the safety, tolerability, pharmacokinetics (affect of the body on the drug), pharmacodynamic (affect of the drug on the body), immunogenicity (development of antibodies against the drug), and preliminary anti-cancer effect of MGD024.

Patients will receive treatment with MGD024 in consecutive 28-day cycles for a study treatment period of up to 12 cycles (approximately 1 year) or until treatment or study discontinuation criteria are met. Response assessments will be performed after Cycle 1 and then after every even numbered cycle starting with Cycle 2 until progression or study treatment discontinuation. Patients will be checked for side effects throughout the study.

A Study of MGD024 in Patients With Relapsed or Refractory Hematologic Malignancies

A Phase 1, First-in-Human, Dose Escalation Study of MGD024, a CD123 x CD3 Bispecific DART Molecule, in Patients With Select Relapsed or Refractory Hematologic Malignancies

Observation of side effects determines the highest safe dose for further study

The highest concentration of MGD024 at the end of the infusion

Number of patients who develop antibodies against MDG024

The proportion of patients with a complete response or a partial response to treatment

The proportion of patient achieving a complete response according to disease-specific criteria

The time between the first dose date to the date of first documented disease-specific progression or death from any cause

The time between the first dose and the date of initial response.

The time between the date of initial response to the date of disease-specific progression or death from any cause

The time between the first dose date to the date of death from any cause

MacroGenics

Infections

Pseudomonas Infections

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Protective Agents

Immunotoxins

Immunotoxin HA22

Immunoconjugates

Immunologic Factors

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.

Moxetumomab pasudotox

IV Bag Protectant for Moxetumomab pasudotox

MedImmune LLC

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.

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.

Moxetumomab Pasudotox for Advanced Hairy Cell Leukemia

A Pivotal Multicenter Trial of Moxetumomab Pasudotox in Relapsed/ Refractory Hairy Cell Leukemia

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.

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.

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.

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.

Time to CR was defined as the time from the start of moxetumomab pasudotox administration to the first documentation of CR.

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.

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.

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.

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.

Time to OR was defined as the time from the start of moxetumomab pasudotox administration to the first documentation of OR (CR or PR).

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.

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.

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.

An Adverse Event (AE) is any unfavourable and unintended sign, symptoms, or diseases temporally associated with use of study drug, whether or not considered related to study drug. A serious adverse event (SAE) is an AE that results in death, initial or prolonged inpatient hospitalization, life-threatening, persistent or significant disability/incapacity, congenital anomaly/birth defect, or an important medical event. TEAEs and TESAEs are defined as AEs and SAEs present at baseline that worsened in intensity after administration of study drug, or events absent at baseline that emerged after administration of study drug.

An abnormal laboratory finding which required an action or intervention by the investigator, or a finding judged by the investigator to represent a change beyond the range of normal physiologic fluctuation were reported as AEs. The TEAEs are defined as AEs present at baseline that worsened in intensity after administration of study drug, or events absent at baseline that emerged after administration of study drug, up to 30 days after the last dose of study drug (approximately 7 months).

An abnormal vital signs that were judged by the investigator to be medically significant were reported as AEs. The TEAEs are defined as AEs present at baseline that worsened in intensity after administration of study drug, or events absent at baseline that emerged after administration of study drug, up to 30 days after the last dose of study drug (approximately 7 months).

An abnormal ECG findings that were judged by the investigator to be medically significant were reported as AEs. The TEAEs are defined as AEs present at baseline that worsened in intensity after administration of study drug, or events absent at baseline that emerged after administration of study drug, up to 30 days after the last dose of study drug (approximately 7 months).

The Tmax of moxetumomab pasudotox is reported.

The Cmax of moxetumomab pasudotox is reported.

The Tlast of moxetumomab pasudotox is reported.

The AUC0-last of moxetumomab pasudotox is reported.

The AUC0-3hr of moxetumomab pasudotox is reported.

The AUC0-inf of moxetumomab pasudotox is reported.

The AUCExt of moxetumomab pasudotox is reported.

The CL of moxetumomab pasudotox is reported.

The t1/2 of moxetumomab pasudotox is reported.

Participants with ADA positive, nAb positive, cluster of differentiation 22 (CD22) positive of ADA positive/NAb positive, and pseudomonas exotoxin 38 (PE38) positive of ADA positive/NAb positive to moxetumomab pasudotox at any visit are reported.

Participants received intravenous infusion of moxetumomab pasudotox 40 µg/kg on Days 1, 3, and 5 of each 28-day cycle for up to 6 cycles, until documentation of complete response, progressive disease, initiation of alternate therapy, or unacceptable toxicity.

Moxetumomab Pasudotox 40 µg/kg

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Intent-to-treat (ITT) population included participants who entered into the study and treated with moxetumomab pasudotox.

Priti Patel

The ITT population included participants who entered into the study and treated with moxetumomab pasudotox.

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

Percentage of Participants With Durable CR by Investigator's Assessment

MRD negative CR

MRD positive CR

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

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

The ITT population included participants who entered into the study and treated with moxetumomab pasudotox. Time to CR was evaluated for participants who achieved CR per independent central review.

Time to CR Assessed by Blinded Independent Central Review

The ITT population included participants who entered into the study and treated with moxetumomab pasudotox. Duration of CR was evaluated for participants who achieved CR per independent central review.

Duration of CR Assessed by Blinded Independent Central Review

The ITT population included participants who entered into the study and treated with moxetumomab pasudotox. Duration of HR was evaluated for participants who achieved HR.

Duration of Hematologic Remission

The ITT population included participants who entered into the study and treated with moxetumomab pasudotox. Time to HR was evaluated for participants in the ITT population who achieved HR.

Time to Hematologic Remission

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

Percentage of Participants With Objective Response by Investigator's Assessment

The ITT population included participants who entered into the study and treated with moxetumomab pasudotox. Time to OR was evaluated for participants who achieved OR per independent central review.

Time to Objective Response Assessed by Blinded Independent Central Review

The ITT population included participants who entered into the study and treated with moxetumomab pasudotox. Duration of OR was evaluated for participants who achieved OR per independent central review.

Duration of Objective Response Assessed by Blinded Independent Central Review

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

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

Any TEAEs

Any TESAEs

Safety population included participants who received at least 1 dose of moxetumomab pasudotox.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Phase II Study of the BRAF Inhibitor, Vemurafenib, Plus Obinutuzumab in Patients With Previously Untreated Classical Hairy Cell Leukemia	NCT03410875	Hairy Cell Leuk... Leukemia Leukemia, Hairy...	Vemurafenib Obinutuzumab	18 Years -	Memorial Sloan Kettering Cancer Center
A Study of MGD024 in Patients With Relapsed or Refractory Hematologic Malignancies	NCT05362773	Leukemia, Acute... Myelodysplastic... Classical Hodgk... Leukemia, B-cel... Leukemia, Hairy... Mastocytosis, A... Blastic Plasmac... Chronic Myeloid...	MGD024	18 Years -	MacroGenics
Moxetumomab Pasudotox for Advanced Hairy Cell Leukemia	NCT01829711	Leukemia, Hairy...	Moxetumomab pas... IV Bag Protecta...	18 Years - 100 Years	MedImmune LLC
A Phase II Study of the BRAF Inhibitor, Vemurafenib, Plus Obinutuzumab in Patients With Previously Untreated Classical Hairy Cell Leukemia	NCT03410875	Hairy Cell Leuk... Leukemia Leukemia, Hairy...	Vemurafenib Obinutuzumab	18 Years -	Memorial Sloan Kettering Cancer Center
A Pilot Study of the Safety and Activity of Escalating Doses of ON 01910.Na in Patients With Relapsed Mantle Cell Lymphoma, Multiple Myeloma, Chronic Lymphocytic Leukemia, and Related Lymphoid Malignancies	NCT00861510	Lymphoma, Mantl... Leukemia, Lymph... Leukemia, Hairy... Waldenstrom Mac... Multiple Myelom...	ON01910 Na	18 Years - 99 Years	National Institutes of Health Clinical Center (CC)
A Phase II Study of the BRAF Inhibitor, Vemurafenib, Plus Obinutuzumab in Patients With Previously Untreated Classical Hairy Cell Leukemia	NCT03410875	Hairy Cell Leuk... Leukemia Leukemia, Hairy...	Vemurafenib Obinutuzumab	18 Years -	Memorial Sloan Kettering Cancer Center
A Study of MGD024 in Patients With Relapsed or Refractory Hematologic Malignancies	NCT05362773	Leukemia, Acute... Myelodysplastic... Classical Hodgk... Leukemia, B-cel... Leukemia, Hairy... Mastocytosis, A... Blastic Plasmac... Chronic Myeloid...	MGD024	18 Years -	MacroGenics

Spots Global Cancer Trial Database for leukemia, hairy cell