Lorvotuzumab Mertansine in Treating Younger Patients With Relapsed or Refractory Wilms Tumor, Rhabdomyosarcoma, Neuroblastoma, Pleuropulmonary Blastoma, Malignant Peripheral Nerve Sheath Tumor, or Synovial Sarcoma

NCT ID: NCT02452554

Last Updated: 2022-01-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 62 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-10-12
• Study Completion Date: 2021-09-30

Brief Summary

This phase II trial studies how well lorvotuzumab mertansine works in treating younger patients with Wilms tumor, rhabdomyosarcoma, neuroblastoma, pleuropulmonary blastoma, malignant peripheral nerve sheath tumor (MPNST), or synovial sarcoma that has returned or that does not respond to treatment. Antibody-drug conjugates, such as lorvotuzumab mertansine, are created by attaching an antibody (protein used by the body?s immune system to fight foreign or diseased cells) to an anti-cancer drug. The antibody is used to recognize tumor cells so the anti-cancer drug can kill them.

Detailed Description

PRIMARY OBJECTIVES:

I. To assess the efficacy of IMGN901 (lorvotuzumab mertansine) in Wilms tumor, rhabdomyosarcoma, neuroblastoma and other cluster of differentiation (CD)56-expressing tumors such as pleuropulmonary blastoma, malignant peripheral nerve sheath tumor (MPNST) and synovial sarcoma.

II. To determine the tolerability of the adult recommended phase 2 dose (RP2D) of IMGN901 administered as an intravenous infusion, administered on days 1 and 8 of a 21-day cycle, to children with refractory Wilms tumor, rhabdomyosarcoma, neuroblastoma, pleuropulmonary blastoma, MPNST, or synovial sarcoma.

III. To define and describe the toxicities of IMGN901 administered on this schedule.

EXPLORATORY OBJECTIVES:

I. To correlate tumor response with tumor CD56+ expression. II. To characterize the pharmacokinetics of IMGN901 in children with refractory cancer, including an assessment of impact on circulating CD56+ peripheral blood cells.

OUTLINE:

Patients receive lorvotuzumab mertansine intravenously (IV) over 1-1.5 hours on days 1 and 8. Treatment repeats every 21 days for up to 17 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 5 years.

Conditions

Pleuropulmonary Blastoma; Recurrent Malignant Peripheral Nerve Sheath Tumor; Recurrent Neuroblastoma; Recurrent Rhabdomyosarcoma; Recurrent Synovial Sarcoma; Wilms Tumor

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment (lorvotuzumab mertansine)

Patients receive lorvotuzumab mertansine IV over 1-1.5 hours on days 1 and 8. Treatment repeats every 21 days for up to 17 courses in the absence of disease progression or unacceptable toxicity.

Group Type: EXPERIMENTAL

Laboratory Biomarker Analysis

Intervention Type: OTHER

Correlative studies

Lorvotuzumab Mertansine

Intervention Type: BIOLOGICAL

Given IV

Pharmacological Study

Intervention Type: OTHER

Correlative studies

Interventions

Laboratory Biomarker Analysis

Correlative studies

Intervention Type: OTHER

Lorvotuzumab Mertansine

Given IV

Intervention Type: BIOLOGICAL

Pharmacological Study

Correlative studies

Intervention Type: OTHER

Other Intervention Names

Anti-Human NCAM-1 Monoclonal Antibody N901; BB-10901; huN901-DM1; IMGN901

Eligibility Criteria

Inclusion Criteria

• Patients must have had histologic verification of one of the malignancies listed below at original diagnosis or at relapse

• Primary strata

• Wilms tumor
• Rhabdomyosarcoma
• Neuroblastoma
• Secondary strata: miscellaneous CD56-expressing tumors:

• Pleuropulmonary blastoma
• Malignant peripheral nerve sheath tumor (MPNST)
• Synovial sarcoma
• Patients must have radiographically measurable disease (with the exception of those with neuroblastoma)

• Measurable disease is defined as the presence of at least one lesion on magnetic resonance imaging (MRI) or computed tomography (CT) scan that can be accurately measured with the longest diameter a minimum of 10 mm in at least one dimension (CT scan slice thickness no greater than 5 mm)
• Note: the following do not qualify as measurable disease:

• Malignant fluid collections (e.g., ascites, pleural effusions)
• Bone marrow infiltration except that detected by metaiodobenzylguanidine (MIBG) scan for neuroblastoma
• Lesions only detected by nuclear medicine studies (e.g., bone, gallium or positron emission tomography [PET] scans) except as noted in patients with neuroblastoma who do not have measurable disease but have MIBG-avid evaluable disease
• Elevated tumor markers in plasma or cerebrospinal fluid (CSF)
• Previously radiated lesions that have not demonstrated clear progression post radiation
• Leptomeningeal lesions that do not meet the measurements noted above
• Patients with neuroblastoma who do not have measurable disease but have MIBG-avid evaluable disease are eligible
• Patients must have a Lansky or Karnofsky performance status score of >= 50, corresponding to Eastern Cooperative Oncology Group (ECOG) categories 0, 1 or 2; use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age; patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
• Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study
• Patients must have received standard treatment appropriate for their tumor type

• Myelosuppressive chemotherapy: patients with solid tumors must not have received myelosuppressive chemotherapy within 3 weeks of enrollment onto this study (6 weeks if prior nitrosourea)
• Hematopoietic growth factors: at least 14 days must have elapsed after receiving pegfilgrastim and least 7 days must have elapsed since the completion of therapy with a non-pegylated growth factor
• Biologic (anti-neoplastic agent): at least 7 days must have elapsed since completion of therapy with a biologic agent; for agents that have known adverse events occurring beyond 7 days after administration, this period prior to enrollment must be extended beyond the time during which adverse events are known to occur
• Monoclonal antibodies: at least 3 half-lives must have elapsed since prior therapy that included a monoclonal antibody
• Radiotherapy: >= 2 weeks must have elapsed since local palliative external beam radiation therapy (XRT) (small port); >= 6 weeks must have elapsed since treatment with therapeutic doses of MIBG; >= 3 months must have elapsed if prior craniospinal XRT was received, if >= 50% of the pelvis was irradiated, or if total body irradiation (TBI) was received; >= 6 weeks must have elapsed if other substantial bone marrow irradiation was given
• Stem cell transplant or rescue without TBI: no evidence of active graft vs. host disease and >= 2 months must have elapsed since transplant
• For patients with solid tumors without bone marrow involvement: peripheral absolute neutrophil count (ANC) >= 1000/uL
• For patients with solid tumors without bone marrow involvement: platelet count >= 100,000/uL (transfusion independent, defined as not receiving platelet transfusions within a 7 day period prior to enrollment)
• For patients with solid tumors and known bone marrow metastatic disease: peripheral absolute neutrophil count (ANC) >= 750/uL
• For patients with solid tumors and known bone marrow metastatic disease: platelet count >= 75,000/uL (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment)
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 or a serum creatinine based on age/gender as follows:

• Age 1 to < 2 years: maximum serum creatinine: 0.6 mg/dL in males and females
• Age 2 to < 6 years: maximum serum creatinine: 0.8 mg/dL in males and females
• Age 6 to < 10 years: maximum serum creatinine: 1 mg/dL in males and females
• Age 10 to < 13 years: maximum serum creatinine: 1.2 mg/dL in males and females
• Age 13 to < 16 years: maximum serum creatinine: 1.5 mg/dL in males and 1.4 mg/dL in females
• Age >= 16 years: maximum serum creatinine: 1.7 mg/dL in males and 1.4 mg/dL in females
• Total bilirubin =< 1.5 x upper limit of normal (ULN) for age
• Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 110 U/L (for the purpose of this study, the ULN for SGPT is 45 U/L)
• Serum albumin >= 2 g/dL
• Shortening fraction of >= 27% by echocardiogram, or ejection fraction of >= 50% by gated radionuclide study
• Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled
• All patients and/or their parents or legal guardians must sign a written informed consent
• All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met

Exclusion Criteria

• Patients who are pregnant or breast-feeding are not eligible for this study; negative pregnancy tests must be obtained in girls who are post-menarchal; males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method for the duration of study therapy and for 4 weeks after the last dose of study therapy; breastfeeding women are excluded
• Concomitant medications

• Corticosteroids: patients requiring corticosteroids who have not been on a stable or decreasing dose of corticosteroid for the 7 days prior to enrollment are not eligible
• Patients who have received previous treatment with IMGN901 are not eligible
• Investigational drugs: patients who are currently receiving another investigational drug are not eligible
• Anti-cancer agents: patients who are currently receiving other anti-cancer agents are not eligible
• Anti-graft-versus-host disease (GVHD) or agents to prevent organ rejection post-transplant: patients who are receiving cyclosporine, tacrolimus or other agents to prevent either graft-versus-host disease post bone marrow transplant or organ rejection post-transplant are not eligible for this trial
• Patients who have a CNS toxicity > grade 2 are not eligible
• Patients must not have known active central nervous system (CNS) metastases; patients with known central nervous system metastases are excluded unless treated surgically or with radiotherapy, and stable with no recurrent lesions for at least 6 months
• Patients who have baseline peripheral neuropathy >= grade 2 are not eligible
• Patients who have an uncontrolled infection are not eligible
• Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible

• Minimum Eligible Age: 12 Months
• Maximum Eligible Age: 30 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Children's Oncology Group

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

James I Geller

Role: PRINCIPAL_INVESTIGATOR

Children's Oncology Group

Locations

Children's Hospital of Alabama

Birmingham, Alabama, United States

Arkansas Children's Hospital

Little Rock, Arkansas, United States

Kaiser Permanente Downey Medical Center

Downey, California, United States

Loma Linda University Medical Center

Loma Linda, California, United States

Children's Hospital Los Angeles

Los Angeles, California, United States

Children's Hospital and Research Center at Oakland

Oakland, California, United States

Children's Hospital of Orange County

Orange, California, United States

University of California Davis Comprehensive Cancer Center

Sacramento, California, United States

Rady Children's Hospital - San Diego

San Diego, California, United States

UCSF Medical Center-Mission Bay

San Francisco, California, United States

Children's Hospital Colorado

Aurora, Colorado, United States

Yale University

New Haven, Connecticut, United States

Alfred I duPont Hospital for Children

Wilmington, Delaware, United States

Children's National Medical Center

Washington D.C., District of Columbia, United States

Golisano Children's Hospital of Southwest Florida

Fort Myers, Florida, United States

Nicklaus Children's Hospital

Miami, Florida, United States

AdventHealth Orlando

Orlando, Florida, United States

Johns Hopkins All Children's Hospital

St. Petersburg, Florida, United States

Children's Healthcare of Atlanta - Egleston

Atlanta, Georgia, United States

Kapiolani Medical Center for Women and Children

Honolulu, Hawaii, United States

Saint Luke's Mountain States Tumor Institute

Boise, Idaho, United States

Lurie Children's Hospital-Chicago

Chicago, Illinois, United States

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, United States

Saint Jude Midwest Affiliate

Peoria, Illinois, United States

Riley Hospital for Children

Indianapolis, Indiana, United States

Saint Vincent Hospital and Health Care Center

Indianapolis, Indiana, United States

University of Kentucky/Markey Cancer Center

Lexington, Kentucky, United States

Ochsner Medical Center Jefferson

New Orleans, Louisiana, United States

Eastern Maine Medical Center

Bangor, Maine, United States

Maine Children's Cancer Program

Scarborough, Maine, United States

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, United States

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

C S Mott Children's Hospital

Ann Arbor, Michigan, United States

Wayne State University/Karmanos Cancer Institute

Detroit, Michigan, United States

Ascension Saint John Hospital

Detroit, Michigan, United States

Helen DeVos Children's Hospital at Spectrum Health

Grand Rapids, Michigan, United States

Children's Hospitals and Clinics of Minnesota - Minneapolis

Minneapolis, Minnesota, United States

University of Minnesota/Masonic Cancer Center

Minneapolis, Minnesota, United States

Mayo Clinic

Rochester, Minnesota, United States

University of Mississippi Medical Center

Jackson, Mississippi, United States

Washington University School of Medicine

St Louis, Missouri, United States

Mercy Hospital Saint Louis

St Louis, Missouri, United States

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, United States

Roswell Park Cancer Institute

Buffalo, New York, United States

Mount Sinai Hospital

New York, New York, United States

NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center

New York, New York, United States

State University of New York Upstate Medical University

Syracuse, New York, United States

Sanford Broadway Medical Center

Fargo, North Dakota, United States

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Rainbow Babies and Childrens Hospital

Cleveland, Ohio, United States

Nationwide Children's Hospital

Columbus, Ohio, United States

Oregon Health and Science University

Portland, Oregon, United States

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, United States

Prisma Health Richland Hospital

Columbia, South Carolina, United States

St. Jude Children's Research Hospital

Memphis, Tennessee, United States

Vanderbilt University/Ingram Cancer Center

Nashville, Tennessee, United States

Dell Children's Medical Center of Central Texas

Austin, Texas, United States

UT Southwestern/Simmons Cancer Center-Dallas

Dallas, Texas, United States

Cook Children's Medical Center

Fort Worth, Texas, United States

Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center

Houston, Texas, United States

Primary Children's Hospital

Salt Lake City, Utah, United States

University of Vermont and State Agricultural College

Burlington, Vermont, United States

Children's Hospital of The King's Daughters

Norfolk, Virginia, United States

Seattle Children's Hospital

Seattle, Washington, United States

Providence Sacred Heart Medical Center and Children's Hospital

Spokane, Washington, United States

West Virginia University Healthcare

Morgantown, West Virginia, United States

University of Wisconsin Hospital and Clinics

Madison, Wisconsin, United States

Children's Hospital of Wisconsin

Milwaukee, Wisconsin, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

NCI-2015-00746

Identifier Type: REGISTRY

Identifier Source: secondary_id

ADVL1522

Identifier Type: -

Identifier Source: secondary_id

ADVL1522

Identifier Type: OTHER

Identifier Source: secondary_id

ADVL1522

Identifier Type: OTHER

Identifier Source: secondary_id

U10CA180886

Identifier Type: NIH

Identifier Source: secondary_id

View Link

ADVL1522

Identifier Type: -

Identifier Source: org_study_id