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

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ClinicalTrials.gov Identifier: NCT02452554
Recruitment Status : Active, not recruiting
First Posted : May 22, 2015
Last Update Posted : March 16, 2018
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Children's Oncology Group

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.

Condition or disease Intervention/treatment Phase
Pleuropulmonary Blastoma Recurrent Malignant Peripheral Nerve Sheath Tumor Recurrent Neuroblastoma Recurrent Rhabdomyosarcoma Recurrent Synovial Sarcoma Wilms Tumor Other: Laboratory Biomarker Analysis Biological: Lorvotuzumab Mertansine Other: Pharmacological Study Phase 2

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.

SECONDARY 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.


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 62 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2 Study of IMGN901 (Lorvotuzumab Mertansine; NSC: 783609) in Children With Relapsed or Refractory Wilms Tumor, Rhabdomyosarcoma, Neuroblastoma, Pleuropulmonary Blastoma, Malignant Peripheral Nerve Sheath Tumor (MPNST) and Synovial Sarcoma
Study Start Date : October 2015
Estimated Primary Completion Date : March 2019
Estimated Study Completion Date : March 2020


Arm Intervention/treatment
Experimental: 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.
Other: Laboratory Biomarker Analysis
Correlative studies

Biological: Lorvotuzumab Mertansine
Given IV
Other Names:
  • Anti-Human NCAM-1 Monoclonal Antibody N901
  • BB-10901
  • huN901-DM1
  • IMGN901

Other: Pharmacological Study
Correlative studies




Primary Outcome Measures :
  1. Incidence of toxicities of lorvotuzumab mertansine, using the NCI Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 12 months (17 courses) ]
    Toxicity tables will be constructed to summarize the observed incidence by type of toxicity and grade. Toxicity information recorded will include the type, severity, time of onset, time of resolution, and the probable association with the study regimen.

  2. Objective response by Response Evaluation Criteria in Solid Tumors version 1.1 [ Time Frame: Up to 18 weeks (6 courses) ]
    The best response of disease will be examined separately in each stratum. A responder is defined as a patient who achieves a best response of partial response or complete response on the study. Response rates will be calculated as the percent of evaluable patients who are responders, and confidence intervals will be constructed accounting for the two-stage design.


Other Outcome Measures:
  1. CD56 expression [ Time Frame: Day 1 and 8 of course 1 prior to lorvotuzumab mertansine ]
    The association between CD56+ expression and response will be evaluated using the exact conditional test of proportions (Fisher's Exact test). Analyses will be descriptive and exploratory and hypotheses generating in nature.

  2. Pharmacokinetic (PK) parameters of lorvotuzumab mertansine [ Time Frame: Pre-treatment, end of infusion, and 2, 6, 24, 48, and 96 hours after end of infusion on day 1 of course 1, and pre-treatment, end of infusion, and 2 and 6 hours after end of infusion on day 8 of course 1 ]
    A descriptive analysis of PK parameters of lorvotuzumab mertansine will be performed to define systemic exposure, drug clearance, and other pharmacokinetic parameters. The PK parameters will be summarized with simple summary statistics, including means, medians, ranges, and standard deviations (if numbers and distribution permit). Analyses will be descriptive and exploratory and hypotheses generating in nature.



Information from the National Library of Medicine

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Ages Eligible for Study:   12 Months to 30 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02452554


  Hide Study Locations
Locations
United States, Alabama
Children's Hospital of Alabama
Birmingham, Alabama, United States, 35233
United States, Arkansas
Arkansas Children's Hospital
Little Rock, Arkansas, United States, 72202-3591
United States, California
Southern California Permanente Medical Group
Downey, California, United States, 90242
Loma Linda University Medical Center
Loma Linda, California, United States, 92354
Children's Hospital Los Angeles
Los Angeles, California, United States, 90027
Children's Hospital and Research Center at Oakland
Oakland, California, United States, 94609-1809
Children's Hospital of Orange County
Orange, California, United States, 92868
University of California Davis Comprehensive Cancer Center
Sacramento, California, United States, 95817
Rady Children's Hospital - San Diego
San Diego, California, United States, 92123
UCSF Medical Center-Mission Bay
San Francisco, California, United States, 94158
United States, Colorado
Children's Hospital Colorado
Aurora, Colorado, United States, 80045
United States, Connecticut
Yale University
New Haven, Connecticut, United States, 06520
United States, Delaware
Alfred I duPont Hospital for Children
Wilmington, Delaware, United States, 19803
United States, District of Columbia
Children's National Medical Center
Washington, District of Columbia, United States, 20010
United States, Florida
Golisano Children's Hospital of Southwest Florida
Fort Myers, Florida, United States, 33908
Nicklaus Children's Hospital
Miami, Florida, United States, 33155
Florida Hospital Orlando
Orlando, Florida, United States, 32803
Johns Hopkins All Children's Hospital
Saint Petersburg, Florida, United States, 33701
United States, Georgia
Children's Healthcare of Atlanta - Egleston
Atlanta, Georgia, United States, 30322
United States, Hawaii
Kapiolani Medical Center for Women and Children
Honolulu, Hawaii, United States, 96826
United States, Idaho
Saint Luke's Mountain States Tumor Institute
Boise, Idaho, United States, 83712
United States, Illinois
Lurie Children's Hospital-Chicago
Chicago, Illinois, United States, 60611
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, United States, 60637
Saint Jude Midwest Affiliate
Peoria, Illinois, United States, 61637
United States, Indiana
Riley Hospital for Children
Indianapolis, Indiana, United States, 46202
Saint Vincent Hospital and Health Care Center
Indianapolis, Indiana, United States, 46260
United States, Kentucky
University of Kentucky/Markey Cancer Center
Lexington, Kentucky, United States, 40536
United States, Louisiana
Ochsner Medical Center Jefferson
New Orleans, Louisiana, United States, 70121
United States, Maine
Eastern Maine Medical Center
Bangor, Maine, United States, 04401
Maine Children's Cancer Program
Scarborough, Maine, United States, 04074
United States, Maryland
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, United States, 21287
United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
United States, Michigan
C S Mott Children's Hospital
Ann Arbor, Michigan, United States, 48109
Wayne State University/Karmanos Cancer Institute
Detroit, Michigan, United States, 48201
Saint John Hospital and Medical Center
Detroit, Michigan, United States, 48236
Helen DeVos Children's Hospital at Spectrum Health
Grand Rapids, Michigan, United States, 49503
United States, Minnesota
Children's Hospitals and Clinics of Minnesota - Minneapolis
Minneapolis, Minnesota, United States, 55404
University of Minnesota/Masonic Cancer Center
Minneapolis, Minnesota, United States, 55455
Mayo Clinic
Rochester, Minnesota, United States, 55905
United States, Mississippi
University of Mississippi Medical Center
Jackson, Mississippi, United States, 39216
United States, Missouri
Washington University School of Medicine
Saint Louis, Missouri, United States, 63110
Mercy Hospital Saint Louis
Saint Louis, Missouri, United States, 63141
United States, New Hampshire
Dartmouth Hitchcock Medical Center
Lebanon, New Hampshire, United States, 03756
United States, New York
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263
Mount Sinai Hospital
New York, New York, United States, 10029
Columbia University/Herbert Irving Cancer Center
New York, New York, United States, 10032
State University of New York Upstate Medical University
Syracuse, New York, United States, 13210
United States, North Dakota
Sanford Medical Center-Fargo
Fargo, North Dakota, United States, 58122
United States, Ohio
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45229
Rainbow Babies and Childrens Hospital
Cleveland, Ohio, United States, 44106
Nationwide Children's Hospital
Columbus, Ohio, United States, 43205
United States, Oregon
Oregon Health and Science University
Portland, Oregon, United States, 97239
United States, Pennsylvania
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, United States, 15224
United States, South Carolina
Palmetto Health Richland
Columbia, South Carolina, United States, 29203
United States, Tennessee
St. Jude Children's Research Hospital
Memphis, Tennessee, United States, 38105
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee, United States, 37232
United States, Texas
Dell Children's Medical Center of Central Texas
Austin, Texas, United States, 78723
UT Southwestern/Simmons Cancer Center-Dallas
Dallas, Texas, United States, 75390
Cook Children's Medical Center
Fort Worth, Texas, United States, 76104
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
Houston, Texas, United States, 77030
United States, Utah
Primary Children's Hospital
Salt Lake City, Utah, United States, 84113
United States, Vermont
University of Vermont College of Medicine
Burlington, Vermont, United States, 05405
United States, Virginia
Childrens Hospital-King's Daughters
Norfolk, Virginia, United States, 23507
United States, Washington
Seattle Children's Hospital
Seattle, Washington, United States, 98105
Providence Sacred Heart Medical Center and Children's Hospital
Spokane, Washington, United States, 99204
United States, West Virginia
West Virginia University Healthcare
Morgantown, West Virginia, United States, 26506
United States, Wisconsin
University of Wisconsin Hospital and Clinics
Madison, Wisconsin, United States, 53792
Children's Hospital of Wisconsin
Milwaukee, Wisconsin, United States, 53226
Sponsors and Collaborators
Children's Oncology Group
National Cancer Institute (NCI)
Investigators
Principal Investigator: James Geller Children's Oncology Group

Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT02452554     History of Changes
Other Study ID Numbers: ADVL1522
NCI-2015-00746 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
ADVL1522
ADVL1522 ( Other Identifier: Children's Oncology Group )
ADVL1522 ( Other Identifier: CTEP )
U10CA180886 ( U.S. NIH Grant/Contract )
First Posted: May 22, 2015    Key Record Dates
Last Update Posted: March 16, 2018
Last Verified: March 2018

Additional relevant MeSH terms:
Neoplasms
Sarcoma
Neuroblastoma
Rhabdomyosarcoma
Wilms Tumor
Sarcoma, Synovial
Nerve Sheath Neoplasms
Neurilemmoma
Neurofibrosarcoma
Pulmonary Blastoma
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neuroectodermal Tumors, Primitive, Peripheral
Neuroectodermal Tumors, Primitive
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Myosarcoma
Neoplasms, Muscle Tissue
Neoplasms, Complex and Mixed
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Neoplastic Syndromes, Hereditary
Kidney Diseases
Urologic Diseases
Genetic Diseases, Inborn