Non Hodgkin Lymphoma Clinical Trial
Tipifarnib for the Treatment of Advanced Solid Tumors, Lymphoma, or Histiocytic Disorders With HRAS Gene Alterations, a Pediatric MATCH Treatment Trial
Summary
This phase II pediatric MATCH trial studies how well tipifarnib works in treating patients with solid tumors that have recurred or spread to other places in the body (advanced), lymphoma, or histiocytic disorders, that have a genetic alteration in the gene HRAS. Tipifarnib may block the growth of cancer cells that have specific genetic changes in a gene called HRAS and may reduce tumor size.
Full Description
PRIMARY OBJECTIVE:
I. To determine the objective response rate (ORR; complete response + partial response) in pediatric patients treated with tipifarnib with advanced solid tumors (including central nervous system [CNS] tumors), lymphomas or histiocytic disorders that harbor activating genetic alterations in HRAS.
SECONDARY OBJECTIVES:
I. To estimate the progression free survival in pediatric patients treated with tipifarnib with advanced solid tumors (including CNS tumors), lymphomas or histiocytic disorders that harbor activating genetic alterations in HRAS.
II. To obtain information about the tolerability of tipifarnib in children and adolescents with relapsed or refractory cancer.
EXPLORATORY OBJECTIVES:
I. To evaluate other biomarkers as predictors of response to tipifarnib and specifically, whether tumors that harbor different missense mutations or variant allele frequency will demonstrate differential response to tipifarnib treatment.
II. To explore approaches to profiling changes in tumor genomics over time through evaluation of circulating tumor deoxyribonucleic acid (DNA).
OUTLINE:
Patients receive tipifarnib orally (PO) or via nasogastric or gastric tube twice daily (BID) on days 1-7 and 15-21. Treatment repeats every 28 days for up to 26 cycles (2 years) in the absence of disease progression or unacceptable toxicity. Patients undergo tumor disease evaluation with positron emission tomography (PET) scan, computed tomography (CT) scan, magnetic resonance imaging (MRI), or meta-iodobenzylguanidine (MIBG) scintigraphy throughout the trial. Patients may undergo bone marrow aspiration or biopsy at baseline, or if there is suspicion of bone marrow metastasis, or when a complete or partial response is identified, or if there is disease progression in the marrow suspected. Patients may undergo blood specimen collections throughout the trial.
After completion of study treatment, patients are followed up at 30 days, then periodically thereafter.
Eligibility Criteria
Inclusion Criteria:
Patient must have enrolled onto APEC1621SC and must have been given a treatment assignment to MATCH to APEC1621M based on the presence of an actionable mutation as defined in APEC1621SC
Patients must be >=12 months and =< 21 years of age at the time of study enrollment
Patients must have a body surface area >= 0.29 m^2 at enrollment
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) positive (+) 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 cerebral spinal 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 radio-pharmaceutical therapy
Patients must not have received prior exposure to tipifarnib
For patients with solid tumors without known bone marrow involvement (within 7 days prior to enrollment):
Peripheral absolute neutrophil count (ANC) >= 1000/mm^3
For patients with solid tumors without known bone marrow involvement (within 7 days prior to enrollment):
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 counts (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 as follows (within 7 days prior to enrollment):
Age: Maximum serum creatinine (mg/dL)
1 to < 2 years: male (0.6), female (0.6)
2 to < 6 years: male (0.8), female (0.8)
6 to < 10 years: male (1), female (1)
10 to < 13 years: male (1.2), female (1.2)
13 to < 16 years: male (1.5), female (1.4)
>= 16 years: 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)
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
Patients must be able to swallow intact tablets or crushed tablets mixed in water, orange juice, apple juice, tomato juice, ginger ale, applesauce, yogurt, protein shake, or a dietary supplement drink (such as Ensure). Percutaneous endoscopic gastrostomy (PEG)-tube or nasogastric tube administration is permitted
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 of fetal and teratogenic adverse events as seen in animal/human studies. 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 two effective contraceptive methods for the duration of study treatment. Both female subjects and male subjects with female partners of child-bearing potential must agree to use a highly effective method of contraception for 2 weeks prior to protocol therapy, during, and at least 4 weeks after last dose of tipifarnib. In addition, since tipifarnib could induce toxicity of male reproductive organs and cause impairment of fertility, sperm cryopreservation should be recommended for male subjects wishing to preserve their fertility following tipifarnib treatment
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 inhibitors of CYP3A4/5 or UGT are not eligible. Strong inducers or inhibitors of CYP3A4/5 or UGT should be avoided from 14 days prior to the 1st dose of tipifarnib to the end of the study. In addition, patients receiving agents that are sensitive or narrow therapeutic range substrates of CYP3A4/5 are not eligible. Note: CYP3A4/5 inducing anti-epileptic drugs and dexamethasone for CNS tumors or metastases, on a stable dose, are allowed
Patients with known hypersensitivity to tipifarnib or any components of the tablet are not eligible
Patients with hypersensitivity to imidazoles, such as clotrimazole, ketoconazole, miconazole and others in this drug class 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 170 Locations for this study
Birmingham Alabama, 35233, United States More Info
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Anchorage Alaska, 99508, United States More Info
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Mesa Arizona, 85202, United States More Info
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Phoenix Arizona, 85016, United States More Info
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Tucson Arizona, 85719, United States More Info
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Little Rock Arkansas, 72202, United States More Info
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Downey California, 90242, United States More Info
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Duarte California, 91010, United States
Loma Linda California, 92354, United States More Info
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Long Beach California, 90806, United States More Info
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Los Angeles California, 90027, United States More Info
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Los Angeles California, 90048, United States More Info
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Los Angeles California, 90095, United States More Info
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Madera California, 93636, United States More Info
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Oakland California, 94609, United States More Info
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Oakland California, 94611, United States More Info
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Orange California, 92868, United States More Info
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Palo Alto California, 94304, United States More Info
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Sacramento California, 95817, United States More Info
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San Diego California, 92123, United States More Info
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San Diego California, 92134, United States More Info
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San Francisco California, 94158, United States More Info
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Torrance California, 90502, United States
Aurora Colorado, 80045, United States More Info
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Denver Colorado, 80218, United States More Info
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Hartford Connecticut, 06106, United States More Info
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New Haven Connecticut, 06520, United States More Info
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Wilmington Delaware, 19803, United States More Info
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Washington District of Columbia, 20007, United States More Info
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Washington District of Columbia, 20010, United States More Info
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Fort Lauderdale Florida, 33316, United States More Info
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Fort Myers Florida, 33908, United States More Info
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Gainesville Florida, 32610, United States More Info
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Hollywood Florida, 33021, United States More Info
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Jacksonville Florida, 32207, United States More Info
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Miami Florida, 33136, United States More Info
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Miami Florida, 33155, United States More Info
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Miami Florida, 33176, United States More Info
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Orlando Florida, 32803, United States More Info
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Orlando Florida, 32806, United States More Info
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Orlando Florida, 32827, United States More Info
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Pensacola Florida, 32504, United States More Info
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Saint Petersburg Florida, 33701, United States More Info
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Tampa Florida, 33606, United States More Info
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Tampa Florida, 33607, United States
West Palm Beach Florida, 33407, United States More Info
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Atlanta Georgia, 30322, United States More Info
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Savannah Georgia, 31404, United States More Info
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Honolulu Hawaii, 96826, United States More Info
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Boise Idaho, 83712, United States More Info
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Chicago Illinois, 60611, United States More Info
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Chicago Illinois, 60612, United States More Info
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Chicago Illinois, 60637, United States More Info
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Maywood Illinois, 60153, United States More Info
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Peoria Illinois, 61637, United States More Info
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Springfield Illinois, 62702, United States More Info
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Indianapolis Indiana, 46202, United States More Info
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Indianapolis Indiana, 46260, United States More Info
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Des Moines Iowa, 50309, United States More Info
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Iowa City Iowa, 52242, United States More Info
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Lexington Kentucky, 40536, United States More Info
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Louisville Kentucky, 40202, United States More Info
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New Orleans Louisiana, 70118, United States More Info
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New Orleans Louisiana, 70121, United States More Info
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Bangor Maine, 04401, United States More Info
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Scarborough Maine, 04074, United States More Info
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Baltimore Maryland, 21201, United States More Info
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Baltimore Maryland, 21215, United States More Info
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Baltimore Maryland, 21287, United States More Info
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Bethesda Maryland, 20892, United States
Boston Massachusetts, 02114, United States More Info
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Boston Massachusetts, 02215, United States More Info
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Worcester Massachusetts, 01655, United States More Info
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Ann Arbor Michigan, 48109, United States More Info
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Detroit Michigan, 48201, United States More Info
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Detroit Michigan, 48201, United States
East Lansing Michigan, 48824, United States More Info
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Grand Rapids Michigan, 49503, United States More Info
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Kalamazoo Michigan, 49007, United States More Info
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Royal Oak Michigan, 48073, United States More Info
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Minneapolis Minnesota, 55404, United States More Info
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Minneapolis Minnesota, 55455, United States More Info
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Rochester Minnesota, 55905, United States
Jackson Mississippi, 39216, United States More Info
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Kansas City Missouri, 64108, United States More Info
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Saint Louis Missouri, 63104, United States More Info
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Saint Louis Missouri, 63110, United States More Info
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Saint Louis Missouri, 63141, United States More Info
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Omaha Nebraska, 68114, United States More Info
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Omaha Nebraska, 68198, United States More Info
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Las Vegas Nevada, 89102, United States More Info
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Las Vegas Nevada, 89109, United States More Info
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Las Vegas Nevada, 89135, United States More Info
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Las Vegas Nevada, 89144, United States More Info
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Reno Nevada, 89502, United States More Info
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Lebanon New Hampshire, 03756, United States More Info
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Hackensack New Jersey, 07601, United States More Info
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Morristown New Jersey, 07960, United States More Info
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New Brunswick New Jersey, 08901, United States More Info
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New Brunswick New Jersey, 08903, United States More Info
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Albany New York, 12208, United States More Info
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Bronx New York, 10467, United States More Info
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Buffalo New York, 14263, United States More Info
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Mineola New York, 11501, United States
New Hyde Park New York, 11040, United States More Info
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New York New York, 10016, United States More Info
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New York New York, 10032, United States More Info
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New York New York, 10065, United States More Info
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New York New York, 10065, United States More Info
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Rochester New York, 14642, United States More Info
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Stony Brook New York, 11794, United States More Info
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Syracuse New York, 13210, United States More Info
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Valhalla New York, 10595, United States More Info
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Asheville North Carolina, 28801, United States More Info
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Chapel Hill North Carolina, 27599, United States More Info
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Charlotte North Carolina, 28203, United States More Info
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Charlotte North Carolina, 28204, United States More Info
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Durham North Carolina, 27710, United States More Info
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Greenville North Carolina, 27834, United States More Info
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Winston-Salem North Carolina, 27157, United States More Info
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Fargo North Dakota, 58122, United States More Info
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Akron Ohio, 44308, United States More Info
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Cincinnati Ohio, 45229, United States More Info
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Cleveland Ohio, 44106, United States More Info
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Cleveland Ohio, 44195, United States More Info
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Columbus Ohio, 43205, United States More Info
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Dayton Ohio, 45404, United States More Info
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Toledo Ohio, 43606, United States More Info
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Oklahoma City Oklahoma, 73104, United States More Info
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Portland Oregon, 97227, United States More Info
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Portland Oregon, 97239, United States More Info
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Allentown Pennsylvania, 18103, United States More Info
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Danville Pennsylvania, 17822, United States More Info
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Philadelphia Pennsylvania, 19104, United States More Info
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Philadelphia Pennsylvania, 19134, United States More Info
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Pittsburgh Pennsylvania, 15224, United States More Info
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Providence Rhode Island, 02903, United States More Info
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Columbia South Carolina, 29203, United States More Info
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Greenville South Carolina, 29605, United States More Info
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Sioux Falls South Dakota, 57117, United States More Info
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Chattanooga Tennessee, 37403, United States More Info
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Knoxville Tennessee, 37916, United States More Info
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Memphis Tennessee, 38105, United States More Info
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Nashville Tennessee, 37203, United States More Info
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Nashville Tennessee, 37232, United States More Info
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Austin Texas, 78723, United States More Info
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Corpus Christi Texas, 78411, United States More Info
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Dallas Texas, 75230, United States More Info
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Dallas Texas, 75390, United States More Info
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El Paso Texas, 79905, United States More Info
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Fort Worth Texas, 76104, United States More Info
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Houston Texas, 77030, United States More Info
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Houston Texas, 77030, United States More Info
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Lubbock Texas, 79410, United States More Info
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Lubbock Texas, 79415, United States More Info
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San Antonio Texas, 78207, United States More Info
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San Antonio Texas, 78229, United States More Info
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San Antonio Texas, 78229, United States More Info
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Temple Texas, 76508, United States More Info
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Salt Lake City Utah, 84113, United States More Info
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Burlington Vermont, 05405, United States More Info
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Falls Church Virginia, 22042, United States More Info
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Norfolk Virginia, 23507, United States More Info
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Portsmouth Virginia, 23708, United States More Info
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Richmond Virginia, 23298, United States More Info
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Seattle Washington, 98105, United States More Info
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Spokane Washington, 99204, United States More Info
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Tacoma Washington, 98405, United States More Info
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Tacoma Washington, 98431, United States More Info
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Morgantown West Virginia, 26506, United States
Madison Wisconsin, 53792, United States More Info
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Marshfield Wisconsin, 54449, United States More Info
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Milwaukee Wisconsin, 53226, United States More Info
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San Juan , 00926, Puerto Rico More Info
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