Kidney Cancer Clinical Trial
Lorvotuzumab Mertansine in Treating Younger Patients With Relapsed or Refractory Wilms Tumor, Rhabdomyosarcoma, Neuroblastoma, Pleuropulmonary Blastoma, Malignant Peripheral Nerve Sheath Tumor, or Synovial Sarcoma
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.
Full 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.
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
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There are 69 Locations for this study
Birmingham Alabama, 35233, United States
Little Rock Arkansas, 72202, United States
Downey California, 90242, United States
Loma Linda California, 92354, United States
Los Angeles California, 90027, United States
Oakland California, 94609, United States
Orange California, 92868, United States
Sacramento California, 95817, United States
San Diego California, 92123, United States
San Francisco California, 94158, United States
Aurora Colorado, 80045, United States
New Haven Connecticut, 06520, United States
Wilmington Delaware, 19803, United States
Washington District of Columbia, 20010, United States
Fort Myers Florida, 33908, United States
Miami Florida, 33155, United States
Orlando Florida, 32803, United States
Saint Petersburg Florida, 33701, United States
Atlanta Georgia, 30322, United States
Honolulu Hawaii, 96826, United States
Boise Idaho, 83712, United States
Chicago Illinois, 60611, United States
Chicago Illinois, 60637, United States
Peoria Illinois, 61637, United States
Indianapolis Indiana, 46202, United States
Indianapolis Indiana, 46260, United States
Lexington Kentucky, 40536, United States
New Orleans Louisiana, 70121, United States
Bangor Maine, 04401, United States
Scarborough Maine, 04074, United States
Baltimore Maryland, 21287, United States
Boston Massachusetts, 02215, United States
Ann Arbor Michigan, 48109, United States
Detroit Michigan, 48201, United States
Detroit Michigan, 48236, United States
Grand Rapids Michigan, 49503, United States
Minneapolis Minnesota, 55404, United States
Minneapolis Minnesota, 55455, United States
Rochester Minnesota, 55905, United States
Jackson Mississippi, 39216, United States
Saint Louis Missouri, 63110, United States
Saint Louis Missouri, 63141, United States
Lebanon New Hampshire, 03756, United States
Buffalo New York, 14263, United States
New York New York, 10029, United States
New York New York, 10032, United States
Syracuse New York, 13210, United States
Fargo North Dakota, 58122, United States
Cincinnati Ohio, 45229, United States
Cleveland Ohio, 44106, United States
Columbus Ohio, 43205, United States
Portland Oregon, 97239, United States
Philadelphia Pennsylvania, 19104, United States
Pittsburgh Pennsylvania, 15224, United States
Columbia South Carolina, 29203, United States
Memphis Tennessee, 38105, United States
Nashville Tennessee, 37232, United States
Austin Texas, 78723, United States
Dallas Texas, 75390, United States
Fort Worth Texas, 76104, United States
Houston Texas, 77030, United States
Salt Lake City Utah, 84113, United States
Burlington Vermont, 05405, United States
Norfolk Virginia, 23507, United States
Seattle Washington, 98105, United States
Spokane Washington, 99204, United States
Morgantown West Virginia, 26506, United States
Madison Wisconsin, 53792, United States
Milwaukee Wisconsin, 53226, United States
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