Non Hodgkin Lymphoma Clinical Trial
Ivosidenib in Treating Patients With Advanced Solid Tumors, Lymphoma, or Histiocytic Disorders With IDH1 Mutations (A Pediatric MATCH Treatment Trial)
Summary
This phase II Pediatric MATCH trial studies how well ivosidenib works in treating patients with solid tumors that have spread to other places in the body (advanced), lymphoma, or histiocytic disorders that have IDH1 genetic alterations (mutations). Ivosidenib may block the growth of cancer cells that have specific genetic changes in an important signaling pathway called the IDH pathway.
Full Description
PRIMARY OBJECTIVE:
I. To determine the objective response rate (ORR; complete response + partial response) in pediatric patients treated with AG-120 (ivosidenib) with advanced solid tumors (including central nervous system [CNS] tumors), lymphomas or histiocytic disorders that harbor activating genetic alterations in the IDH1 pathway.
SECONDARY OBJECTIVES:
I. To estimate the progression free survival in pediatric patients treated with AG-120 (ivosidenib) with advanced solid tumors (including CNS tumors), lymphomas or histiocytic disorders that harbor activating genetic alterations in the IDH1 pathway.
II. To obtain information about the tolerability of AG-120 (ivosidenib) in children and adolescents with relapsed or refractory cancer.
III. To provide preliminary estimates of the pharmacokinetics and pharmacodynamics of AG-120 (ivosidenib) in children and adolescents with relapsed or refractory cancer.
EXPLORATORY OBJECTIVES:
I. To evaluate other biomarkers as predictors of response to AG-120 (ivosidenib) and specifically, whether tumors that harbor different missense mutations or fusions will demonstrate differential response to AG-120 (ivosidenib) treatment.
II. To explore approaches to the profiling changes in tumor genomics over time through evaluation of circulating tumor deoxyribonucleic acid (DNA).
OUTLINE:
Patients receive ivosidenib orally (PO) once daily (QD). Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up periodically.
Eligibility Criteria
Inclusion Criteria:
Patient must have enrolled onto APEC1621SC and must have been given a treatment assignment to MATCH to APEC1621K based on the presence of an actionable mutation as defined in APEC1621SC
Patients must be >= than 12 months and =< 21 years of age at the time of study enrollment
Patients must have a body surface area >= 0.78 m^2 at enrollment
Patients must be able to swallow intact tablets
Patients must have radiographically measurable disease at the time of study enrollment. Patients with neuroblastoma who do not have measurable disease but have metaiodobenzylguanidine (MIBG)+ evaluable disease are eligible. Measurable disease in patients with CNS involvement is defined as any lesion that is at minimum 10 mm in one dimension on standard magnetic resonance imaging (MRI) or computed tomography (CT)
Note: The following do not qualify as measurable disease:
Malignant fluid collections (e.g., ascites, pleural effusions)
Bone marrow infiltration except that detected by MIBG scan for neuroblastoma
Lesions only detected by nuclear medicine studies (e.g., bone, gallium or positron emission tomography [PET] scans) except as noted for neuroblastoma
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 measurement requirements for Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
Karnofsky >= 50% for patients > 16 years of age and Lansky >= 50 for patients =< 16 years of age. Note: Neurologic deficits in patients with CNS tumors must have been relatively stable for at least 7 days prior to study enrollment. 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 anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment. If after the required timeframe, the numerical eligibility criteria are met, e.g. blood count criteria, the patient is considered to have recovered adequately
Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive. >= 21 days after the last dose of cytotoxic or myelosuppressive chemotherapy (42 days if prior nitrosourea)
Anti-cancer agents not known to be myelosuppressive (e.g. not associated with reduced platelet or absolute neutrophil count [ANC] counts): >= 7 days after the last dose of agent
Antibodies: >= 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to grade =< 1
Corticosteroids: If used to modify immune adverse events related to prior therapy, >= 14 days must have elapsed since last dose of corticosteroid
Hematopoietic growth factors: >= 14 days after the last dose of a long-acting growth factor (e.g. pegfilgrastim) or 7 days for short-acting growth factor. For growth factors that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur. The duration of this interval must be discussed with the study chair and the study-assigned research coordinator
Interleukins, interferons and cytokines (other than hematopoietic growth factors): >= 21 days after the completion of interleukins, interferon or cytokines (other than hematopoietic growth factors)
Stem cell infusions (with or without total body irradiation [TBI]):
Allogeneic (non-autologous) bone marrow or stem cell transplant, or any stem cell infusion including donor lymphocyte infusion (DLI) or boost infusion: >= 84 days after infusion and no evidence of graft versus host disease (GVHD)
Autologous stem cell infusion including boost infusion: >= 42 days
Cellular Therapy: >= 42 days after the completion of any type of cellular therapy (e.g. modified T cells, natural killer [NK] cells, dendritic cells, etc.)
Radiation therapy (XRT)/external beam Irradiation including protons: >= 14 days after local XRT; >= 150 days after TBI, craniospinal XRT or if radiation to >= 50% of the pelvis; >= 42 days if other substantial bone marrow (BM) radiation
Note: Radiation may not be delivered to "measurable disease" tumor site(s) being used to follow response to subprotocol treatment
Radiopharmaceutical therapy (e.g., radiolabeled antibody, 131I-MIBG): >= 42 days after systemically administered radiopharmaceutical therapy
Patients must not have received prior exposure to AG-120 (ivosidenib) or other IDH1 inhibitors
For patients with solid tumors without known bone marrow involvement: Peripheral absolute neutrophil count (ANC) >= 1000/mm^3 (within 7 days prior to enrollment)
For patients with solid tumors without known bone marrow involvement: Platelet count >= 100,000/mm^3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment)
Patients with known bone marrow metastatic disease will be eligible for study provided they meet the blood count (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions). These patients will not be evaluable for hematologic toxicity
Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 ml/min/1.73 m^2 (within 7 days prior to enrollment), or
A serum creatinine based on age/gender (within 7 days prior to enrollment)
Age 1 to < 2 years, maximum serum creatinine (mg/dL) male 0.6, female 0.6
Age 2 to < 6 years, maximum serum creatinine (mg/dL) male 0.8, female 0.8
Age 6 to < 10 years, maximum serum creatinine (mg/dL) male 1, female 1
Age 10 to < 13 years, maximum serum creatinine (mg/dL) male 1.2, female 1.2
Age 13 to < 16 years, maximum serum creatinine (mg/dL) male 1.5, female 1.4
Age >= 16 years, maximum serum creatinine (mg/dL) male 1.7, female 1.4
Bilirubin (sum of conjugated + unconjugated) =< 1.5 x upper limit of normal (ULN) for age (within 7 days prior to enrollment)
Serum glutamate-pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 135 U/L. (For the purpose of this study, the ULN for SGPT is 45 U/L) (within 7 days prior to enrollment)
Serum albumin >= 2 g/dL (within 7 days prior to enrollment)
Corrected QT (QTc )interval =< 450 milliseconds (within 7 days prior to enrollment)
Note: Patients should avoid concomitant medication known or suspected to prolong QTc interval or cause Torsades de Pointes. Patients who are receiving drugs that prolong the QTc are eligible if the drug is necessary and no alternatives are available
Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled
Nervous system disorders (Common Terminology Criteria for Adverse Events [CTCAE] version [v]5.0) resulting from prior therapy must be =< grade 2, with the exception of decreased tendon reflex (DTR). Any grade of DTR is eligible
All patients and/or their parents or legally authorized representatives must sign a written informed consent. Assent, when appropriate, will be obtained according to institutional guidelines
Exclusion Criteria:
Pregnant or breast-feeding women will not be entered on this study due to risks because there is yet no available information regarding human fetal or teratogenic toxicities. 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 non-hormonal contraceptive method for the duration of study treatment and for at least 1 month after last dose of AG-120 (ivosidenib). Since AG-120 (ivosidenib) may decrease concentrations of hormonal contraceptives, hormonal contraceptives are not considered effective contraception when co-administered with AG-120 (ivosidenib)
Patients receiving corticosteroids who have not been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment are not eligible. If used to modify immune adverse events related to prior therapy, >= 14 days must have elapsed since last dose of corticosteroid
Patients who are currently receiving another investigational drug are not eligible
Patients who are currently receiving other anti-cancer agents are not eligible
Patients who are receiving cyclosporine, tacrolimus or other agents to prevent graft-versus-host disease post bone marrow transplant are not eligible for this trial
Patients who are currently receiving drugs that are strong inducers or moderate to strong inhibitors of CYP3A4 are not eligible. Strong inducers or moderate to strong inhibitors of CYP3A4 should be avoided from 14 days prior to enrollment to the end of the study. Note: CYP3A4 inducing anti-epileptic drugs and dexamethasone for CNS tumors or metastases, on a stable dose, are allowed. In addition, patients receiving sensitive or narrow therapeutic range substrates of CYP3A4 are not eligible
Patients with a history of progressive multifocal leukoencephalopathy are not eligible
Patients who have an uncontrolled infection are not eligible
Patients who have received a prior solid organ transplantation 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 172 Locations for this study
Birmingham Alabama, 35233, United States
Anchorage Alaska, 99508, United States
Mesa Arizona, 85202, United States
Phoenix Arizona, 85016, United States
Tucson Arizona, 85719, United States
Little Rock Arkansas, 72202, United States
Downey California, 90242, United States
Duarte California, 91010, United States
Loma Linda California, 92354, United States
Long Beach California, 90806, United States
Los Angeles California, 90027, United States
Los Angeles California, 90048, United States
Los Angeles California, 90095, United States
Madera California, 93636, United States
Oakland California, 94609, United States
Oakland California, 94611, United States
Orange California, 92868, United States
Palo Alto California, 94304, United States
Sacramento California, 95817, United States
San Diego California, 92123, United States
San Diego California, 92134, United States
San Francisco California, 94158, United States
Torrance California, 90502, United States
Aurora Colorado, 80045, United States
Denver Colorado, 80218, United States
Hartford Connecticut, 06106, United States
New Haven Connecticut, 06520, United States
Wilmington Delaware, 19803, United States
Washington District of Columbia, 20007, United States
Washington District of Columbia, 20010, United States
Fort Lauderdale Florida, 33316, United States
Fort Myers Florida, 33908, United States
Gainesville Florida, 32610, United States
Hollywood Florida, 33021, United States
Jacksonville Florida, 32207, United States
Miami Florida, 33136, United States
Miami Florida, 33155, United States
Miami Florida, 33176, United States
Orlando Florida, 32803, United States
Orlando Florida, 32806, United States
Orlando Florida, 32827, United States
Pensacola Florida, 32504, United States
Saint Petersburg Florida, 33701, United States
Tampa Florida, 33606, United States
Tampa Florida, 33607, United States
West Palm Beach Florida, 33407, United States
Atlanta Georgia, 30322, United States
Savannah Georgia, 31404, United States
Honolulu Hawaii, 96826, United States
Boise Idaho, 83712, United States
Chicago Illinois, 60611, United States
Chicago Illinois, 60612, United States
Chicago Illinois, 60637, United States
Maywood Illinois, 60153, United States
Peoria Illinois, 61637, United States
Springfield Illinois, 62702, United States
Indianapolis Indiana, 46202, United States
Indianapolis Indiana, 46260, United States
Des Moines Iowa, 50309, United States
Iowa City Iowa, 52242, United States
Lexington Kentucky, 40536, United States
Louisville Kentucky, 40202, United States
New Orleans Louisiana, 70118, United States
New Orleans Louisiana, 70121, United States
Bangor Maine, 04401, United States
Scarborough Maine, 04074, United States
Baltimore Maryland, 21201, United States
Baltimore Maryland, 21215, United States
Baltimore Maryland, 21287, United States
Bethesda Maryland, 20892, United States
Boston Massachusetts, 02114, United States
Boston Massachusetts, 02215, United States
Worcester Massachusetts, 01655, United States
Ann Arbor Michigan, 48109, United States
Detroit Michigan, 48201, United States
Detroit Michigan, 48201, United States
East Lansing Michigan, 48824, United States
Grand Rapids Michigan, 49503, United States
Kalamazoo Michigan, 49007, United States
Royal Oak Michigan, 48073, United States
Minneapolis Minnesota, 55404, United States
Minneapolis Minnesota, 55455, United States
Rochester Minnesota, 55905, United States
Jackson Mississippi, 39216, United States
Kansas City Missouri, 64108, United States
Saint Louis Missouri, 63104, United States
Saint Louis Missouri, 63110, United States
Saint Louis Missouri, 63141, United States
Omaha Nebraska, 68114, United States
Omaha Nebraska, 68198, United States
Las Vegas Nevada, 89102, United States
Las Vegas Nevada, 89109, United States
Las Vegas Nevada, 89135, United States
Las Vegas Nevada, 89144, United States
Reno Nevada, 89502, United States
Lebanon New Hampshire, 03756, United States
Hackensack New Jersey, 07601, United States
Morristown New Jersey, 07960, United States
New Brunswick New Jersey, 08901, United States
New Brunswick New Jersey, 08903, United States
Albany New York, 12208, United States
Bronx New York, 10467, United States
Buffalo New York, 14263, United States
Mineola New York, 11501, United States
New Hyde Park New York, 11040, United States
New York New York, 10016, United States
New York New York, 10032, United States
New York New York, 10065, United States
New York New York, 10065, United States
Rochester New York, 14642, United States
Stony Brook New York, 11794, United States
Syracuse New York, 13210, United States
Valhalla New York, 10595, United States
Asheville North Carolina, 28801, United States
Chapel Hill North Carolina, 27599, United States
Charlotte North Carolina, 28203, United States
Charlotte North Carolina, 28204, United States
Durham North Carolina, 27710, United States
Greenville North Carolina, 27834, United States
Winston-Salem North Carolina, 27157, United States
Fargo North Dakota, 58122, United States
Akron Ohio, 44308, United States
Cincinnati Ohio, 45229, United States
Cleveland Ohio, 44106, United States
Cleveland Ohio, 44195, United States
Columbus Ohio, 43205, United States
Dayton Ohio, 45404, United States
Toledo Ohio, 43606, United States
Oklahoma City Oklahoma, 73104, United States
Portland Oregon, 97227, United States
Portland Oregon, 97239, United States
Allentown Pennsylvania, 18103, United States
Danville Pennsylvania, 17822, United States
Philadelphia Pennsylvania, 19104, United States
Philadelphia Pennsylvania, 19134, United States
Pittsburgh Pennsylvania, 15224, United States
Providence Rhode Island, 02903, United States
Columbia South Carolina, 29203, United States
Greenville South Carolina, 29605, United States
Sioux Falls South Dakota, 57117, United States
Chattanooga Tennessee, 37403, United States
Knoxville Tennessee, 37916, United States
Memphis Tennessee, 38105, United States
Nashville Tennessee, 37203, United States
Nashville Tennessee, 37232, United States
Austin Texas, 78723, United States
Corpus Christi Texas, 78411, United States
Dallas Texas, 75230, United States
Dallas Texas, 75390, United States
El Paso Texas, 79905, United States
Fort Worth Texas, 76104, United States
Houston Texas, 77030, United States
Houston Texas, 77030, United States
Lubbock Texas, 79410, United States
Lubbock Texas, 79415, United States
San Antonio Texas, 78207, United States
San Antonio Texas, 78229, United States
Temple Texas, 76508, United States
Salt Lake City Utah, 84113, United States
Burlington Vermont, 05405, United States
Falls Church Virginia, 22042, United States
Norfolk Virginia, 23507, United States
Portsmouth Virginia, 23708, United States
Richmond Virginia, 23298, United States
Seattle Washington, 98105, United States
Spokane Washington, 99204, United States
Tacoma Washington, 98405, United States
Tacoma Washington, 98431, United States
Morgantown West Virginia, 26506, United States
Madison Wisconsin, 53792, United States
Marshfield Wisconsin, 54449, United States
Milwaukee Wisconsin, 53226, United States
Perth Western Australia, 6009, Australia
San Juan , 00912, Puerto Rico
San Juan , 00926, Puerto Rico
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