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Crizotinib and Combination Chemotherapy in Treating Younger Patients With Relapsed or Refractory Solid Tumors or Anaplastic Large Cell Lymphoma

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ClinicalTrials.gov Identifier: NCT01606878
Recruitment Status : Completed
First Posted : May 28, 2012
Last Update Posted : February 26, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Children's Oncology Group

Brief Summary:
This phase I trial studies the side effects and the best dose of crizotinib when given together with combination chemotherapy in treating younger patients with solid tumors or anaplastic large cell lymphoma that has returned or does not respond to treatment. Crizotinib may stop the growth of tumor or cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as cyclophosphamide, topotecan hydrochloride, dexrazoxane hydrochloride, doxorubicin hydrochloride, and vincristine sulfate, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving crizotinib together with combination chemotherapy may be a better treatment for patients with solid tumors or anaplastic large cell lymphoma.

Condition or disease Intervention/treatment Phase
Childhood Solid Neoplasm Recurrent Childhood Anaplastic Large Cell Lymphoma Recurrent Neuroblastoma Drug: Crizotinib Drug: Cyclophosphamide Drug: Dexrazoxane Hydrochloride Drug: Doxorubicin Hydrochloride Other: Laboratory Biomarker Analysis Other: Pharmacological Study Other: Questionnaire Administration Drug: Topotecan Hydrochloride Drug: Vincristine Sulfate Phase 1

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Detailed Description:

PRIMARY OBJECTIVES:

I. To estimate the recommended phase 2 dose (RP2D) or maximum tolerated dose (MTD) of crizotinib administered orally twice daily in combination with topotecan (topotecan hydrochloride) and cyclophosphamide in children with refractory/relapsed solid tumors or anaplastic large cell lymphoma (ALCL).

II. To define and describe the toxicities of crizotinib in combination with topotecan and cyclophosphamide administered on this schedule.

III. To estimate the recommended phase 2 dose (RP2D) or maximum tolerated dose (MTD) of crizotinib administered orally twice daily in combination with vincristine (vincristine sulfate) and doxorubicin (doxorubicin hydrochloride)/dexrazoxane (dexrazoxane hydrochloride) in children with refractory/relapsed solid tumors or ALCL.

IV. To define and describe the toxicities of crizotinib in combination with vincristine and doxorubicin/dexrazoxane administered on this schedule.

V. To characterize the pharmacokinetics of crizotinib in children with relapsed/refractory cancer when combined with either topotecan and cyclophosphamide or vincristine and doxorubicin/dexrazoxane.

SECONDARY OBJECTIVES:

I. To preliminarily define the antitumor activity of crizotinib in combination with either topotecan and cyclophosphamide or vincristine and doxorubicin/dexrazoxane within the confines of a Phase 1 study.

II. To preliminarily examine the relationship between anaplastic lymphoma kinase (ALK) status in patients with neuroblastoma or ALCL and response to crizotinib in combination with either topotecan and cyclophosphamide or vincristine and doxorubicin/dexrazoxane.

III. To preliminarily examine the relationship between minimal residual disease (MRD) status and clinical response to crizotinib in combination with either topotecan and cyclophosphamide or vincristine and doxorubicin/dexrazoxane in patients with ALCL.

IV. To use a questionnaire to gather preliminary information on the palatability of the oral solution formulation of crizotinib.

V. To examine ALK and MET proto-oncogene (c-Met) expression, copy number and mutations status in archival tumor tissue from solid tumor and ALCL patients.

VI. To use a questionnaire to gather information on the acceptability of the crizotinib capsule formulation.

OUTLINE: This is a dose-escalation study of crizotinib. Patients are assigned to Part A or Part B based on the treating physician's choice and availability of a reservation. After closure of Part A and Part B, patients are assigned to Part C.

PART A (CLOSED TO ACCRUAL 10/3/14): Patients receive crizotinib (oral solution) orally (PO) twice daily (BID) on days 1-21, cyclophosphamide intravenously (IV) once daily (QD) on days 1-5, and topotecan hydrochloride IV QD on days 1-5. Treatment repeats every 21 days for up to 35 courses in the absence of disease progression or unacceptable toxicity.

PART B (CLOSED TO ACCRUAL 10/3/14): Patients receive crizotinib (oral solution) PO BID as in Part A. Patients also receive vincristine sulfate IV on day 1, dexrazoxane hydrochloride IV on day 1, and doxorubicin hydrochloride IV over 15 minutes on day 1. Treatment repeats every 21 days for up to 35 courses in the absence of disease progression or unacceptable toxicity.

PART C: Patients receive crizotinib (capsule formulation) PO BID, cyclophosphamide IV QD, and topotecan hydrochloride IV QD as in Part A. Treatment repeats every 21 days for up to 35 courses in the absence of disease progression or unacceptable toxicity.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 46 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 Study of Crizotinib in Combination With Conventional Chemotherapy for Relapsed or Refractory Solid Tumors or Anaplastic Large Cell Lymphoma
Actual Study Start Date : April 29, 2013
Actual Primary Completion Date : December 31, 2018
Actual Study Completion Date : December 31, 2018


Arm Intervention/treatment
Experimental: Part A (crizotinib, cyclophosphamide, topotecan hydrochloride)
Patients receive crizotinib (oral solution) PO BID on days 1-21, cyclophosphamide IV QD on days 1-5, and topotecan hydrochloride IV QD on days 1-5. Treatment repeats every 21 days for up to 35 courses in the absence of disease progression or unacceptable toxicity. (closed to accrual 10/3/14)
Drug: Crizotinib
Given PO
Other Names:
  • MET Tyrosine Kinase Inhibitor PF-02341066
  • PF-02341066
  • PF-2341066
  • Xalkori

Drug: Cyclophosphamide
Given IV
Other Names:
  • (-)-Cyclophosphamide
  • 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate
  • Carloxan
  • Ciclofosfamida
  • Ciclofosfamide
  • Cicloxal
  • Clafen
  • Claphene
  • CP monohydrate
  • CTX
  • CYCLO-cell
  • Cycloblastin
  • Cycloblastine
  • Cyclophospham
  • Cyclophosphamid monohydrate
  • Cyclophosphamidum
  • Cyclophosphan
  • Cyclophosphane
  • Cyclophosphanum
  • Cyclostin
  • Cyclostine
  • Cytophosphan
  • Cytophosphane
  • Cytoxan
  • Fosfaseron
  • Genoxal
  • Genuxal
  • Ledoxina
  • Mitoxan
  • Neosar
  • Revimmune
  • Syklofosfamid
  • WR- 138719

Other: Laboratory Biomarker Analysis
Correlative studies

Other: Pharmacological Study
Correlative studies

Other: Questionnaire Administration
Ancillary studies

Drug: Topotecan Hydrochloride
Given IV
Other Names:
  • Hycamptamine
  • Hycamtin
  • SKF S-104864-A
  • Topotecan HCl
  • topotecan hydrochloride (oral)

Experimental: Part B (crizotinib, vincristine, dexrazoxane, doxorubicin)
Patients receive crizotinib (oral solution) PO BID as in Part A. Patients also receive vincristine sulfate IV on day 1, dexrazoxane hydrochloride IV on day 1, and doxorubicin hydrochloride IV over 15 minutes on day 1. Treatment repeats every 21 days for up to 35 courses in the absence of disease progression or unacceptable toxicity. (closed to accrual 10/3/14)
Drug: Crizotinib
Given PO
Other Names:
  • MET Tyrosine Kinase Inhibitor PF-02341066
  • PF-02341066
  • PF-2341066
  • Xalkori

Drug: Dexrazoxane Hydrochloride
Given IV
Other Names:
  • Cardioxane
  • Totect
  • Zinecard

Drug: Doxorubicin Hydrochloride
Given IV
Other Names:
  • 5,12-Naphthacenedione, 10-[(3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy]-7,8, 9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-, hydrochloride, (8S-cis)- (9CI)
  • ADM
  • Adriacin
  • Adriamycin
  • Adriamycin Hydrochloride
  • Adriamycin PFS
  • Adriamycin RDF
  • ADRIAMYCIN, HYDROCHLORIDE
  • Adriamycine
  • Adriblastina
  • Adriblastine
  • Adrimedac
  • Chloridrato de Doxorrubicina
  • DOX
  • DOXO-CELL
  • Doxolem
  • Doxorubicin.HCl
  • Doxorubin
  • Farmiblastina
  • FI 106
  • FI-106
  • hydroxydaunorubicin
  • Rubex

Other: Laboratory Biomarker Analysis
Correlative studies

Other: Pharmacological Study
Correlative studies

Other: Questionnaire Administration
Ancillary studies

Drug: Vincristine Sulfate
Given IV
Other Names:
  • Kyocristine
  • Leurocristine sulfate
  • Leurocristine, sulfate
  • Oncovin
  • Vincasar
  • Vincosid
  • Vincrex
  • Vincristine, sulfate

Experimental: Part C (crizotinib, cyclophosphamide, topotecan hydrochloride)
Patients receive crizotinib (capsule formulation) PO BID, cyclophosphamide IV QD, and topotecan hydrochloride IV QD as in Part A. Treatment repeats every 21 days for up to 35 courses in the absence of disease progression or unacceptable toxicity.
Drug: Crizotinib
Given PO
Other Names:
  • MET Tyrosine Kinase Inhibitor PF-02341066
  • PF-02341066
  • PF-2341066
  • Xalkori

Drug: Cyclophosphamide
Given IV
Other Names:
  • (-)-Cyclophosphamide
  • 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate
  • Carloxan
  • Ciclofosfamida
  • Ciclofosfamide
  • Cicloxal
  • Clafen
  • Claphene
  • CP monohydrate
  • CTX
  • CYCLO-cell
  • Cycloblastin
  • Cycloblastine
  • Cyclophospham
  • Cyclophosphamid monohydrate
  • Cyclophosphamidum
  • Cyclophosphan
  • Cyclophosphane
  • Cyclophosphanum
  • Cyclostin
  • Cyclostine
  • Cytophosphan
  • Cytophosphane
  • Cytoxan
  • Fosfaseron
  • Genoxal
  • Genuxal
  • Ledoxina
  • Mitoxan
  • Neosar
  • Revimmune
  • Syklofosfamid
  • WR- 138719

Other: Laboratory Biomarker Analysis
Correlative studies

Other: Pharmacological Study
Correlative studies

Other: Questionnaire Administration
Ancillary studies

Drug: Topotecan Hydrochloride
Given IV
Other Names:
  • Hycamptamine
  • Hycamtin
  • SKF S-104864-A
  • Topotecan HCl
  • topotecan hydrochloride (oral)




Primary Outcome Measures :
  1. Incidence of adverse events [ Time Frame: Up to 30 days post-treatment ]
    A descriptive summary of all toxicities will be reported as assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.

  2. Maximum tolerated dose (MTD) of crizotinib [ Time Frame: 21 days ]
    The MTD of crizotinib administered with combination chemotherapy based on the incidence of dose-limiting toxicity (DLT) at which fewer than one-third of patients experience DLT, as assessed by NCI CTCAE version 4.0.


Secondary Outcome Measures :
  1. Time to maximum plasma concentration (Tmax) [ Time Frame: Time Frame: Prior to first dose on day 1 of course 1 and at pre-dose (12 hours after last dose), 1, 2, 4, and 6-8 hours post-dose between days 15 and 21 of course 1 ]
    Crizotinib plasma concentrations will be measured at a centralized laboratory using a validated liquid chromatography/tandem mass spectrometry assay. Pharmacokinetic (PK) parameters (Tmax, peak concentration [Cmax], half-life [t1/2], area under the curve [AUC], plasma clarance [Cl/F]) of crizotinib will be calculated using standard non-compartmental or compartmental methods and summarized with descriptive summary statistics, including means, medians, ranges, and standard deviations (if numbers and distribution permit).

  2. Peak concentration (Cmax) [ Time Frame: Time Frame: Prior to first dose on day 1 of course 1 and at pre-dose (12 hours after last dose), 1, 2, 4, and 6-8 hours post-dose between days 15 and 21 of course 1 ]
    Crizotinib plasma concentrations will be measured at a centralized laboratory using a validated liquid chromatography/tandem mass spectrometry assay. PK parameters (Tmax, Cmax, t1/2, AUC, Cl/F) of crizotinib will be calculated using standard non-compartmental or compartmental methods and summarized with descriptive summary statistics, including means, medians, ranges, and standard deviations (if numbers and distribution permit).

  3. Terminal phase half-life (t1/2) [ Time Frame: Time Frame: Prior to first dose on day 1 of course 1 and at pre-dose (12 hours after last dose), 1, 2, 4, and 6-8 hours post-dose between days 15 and 21 of course 1 ]
    Crizotinib plasma concentrations will be measured at a centralized laboratory using a validated liquid chromatography/tandem mass spectrometry assay. PK parameters (Tmax, Cmax, t1/2, AUC, Cl/F) of crizotinib will be calculated using standard non-compartmental or compartmental methods and summarized with descriptive summary statistics, including means, medians, ranges, and standard deviations (if numbers and distribution permit).

  4. Area under the concentration [ Time Frame: Time Frame: Prior to first dose on day 1 of course 1 and at pre-dose (12 hours after last dose), 1, 2, 4, and 6-8 hours post-dose between days 15 and 21 of course 1 ]
    Crizotinib plasma concentrations will be measured at a centralized laboratory using a validated liquid chromatography/tandem mass spectrometry assay. PK parameters (Tmax, Cmax, t1/2, AUC, Cl/F) of crizotinib will be calculated using standard non-compartmental or compartmental methods and summarized with descriptive summary statistics, including means, medians, ranges, and standard deviations (if numbers and distribution permit).

  5. Plasma Clearance (CI/F) [ Time Frame: Time Frame: Prior to first dose on day 1 of course 1 and at pre-dose (12 hours after last dose), 1, 2, 4, and 6-8 hours post-dose between days 15 and 21 of course 1 ]
    Crizotinib plasma concentrations will be measured at a centralized laboratory using a validated liquid chromatography/tandem mass spectrometry assay. PK parameters (Tmax, Cmax, t1/2, AUC, Cl/F) of crizotinib will be calculated using standard non-compartmental or compartmental methods and summarized with descriptive summary statistics, including means, medians, ranges, and standard deviations (if numbers and distribution permit).

  6. Response rate [ Time Frame: Up to 2 years ]
    Disease Response Rate (occurrence of PR/CR) assessed according to Response Evaluation Criteria in Solid Tumors version 1.1 Will be reported descriptively.



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Layout table for eligibility information
Ages Eligible for Study:   13 Months to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must have had histologic verification of malignancy at original diagnosis or relapse; all patients with relapsed or refractory solid tumors or anaplastic large cell lymphoma (ALCL) are eligible except for patients with primary or metastatic central nervous system (CNS) tumors or patients with primary cutaneous ALCL
  • Patients must have either measurable or evaluable disease
  • Patient?s current disease state must be one for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life
  • Karnofsky >= 60% for patients > 16 years of age and Lansky >= 50 for patients =< 16 years of age; Note: 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 chemotherapy

    • Myelosuppressive chemotherapy:

      • Solid tumors: at least 21 days after the last dose of myelosuppressive chemotherapy (42 days if prior nitrosourea)
      • ALCL:

        • Patients with ALCL who relapse while receiving standard maintenance chemotherapy will not be required to have a waiting period before enrollment onto this study
        • Patients who relapse while they are not receiving standard maintenance therapy, must have fully recovered from all acute toxic effects of prior therapy; at least 14 days must have elapsed after the completion of cytotoxic therapy
    • Hematopoietic growth factors: at least 14 days after the last dose of a long-acting growth factor (e.g. Neulasta) or 7 days for short-acting growth factor; for agents 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
    • Biologic (anti-neoplastic agent): at least 7 days after the last dose of a biologic agent; for agents 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
    • Immunotherapy: at least 42 days after the completion of any type of immunotherapy, e.g. tumor vaccines
    • Monoclonal antibodies: at least 3 half-lives of the antibody after the last dose of a monoclonal antibody
    • Radiation therapy (XRT):

      • Solid tumors: at least 14 days after local palliative XRT (small port); >= 6 weeks must have elapsed since treatment with therapeutic doses of metaiodobenzylguanidine (MIBG); at least 150 days must have elapsed if prior total body irradiation (TBI), craniospinal XRT or if >= 50% radiation of pelvis; at least 42 days must have elapsed if other substantial bone marrow (BM) radiation
      • ALCL: at least 14 days after local palliative XRT (small port); at least 84 days must have elapsed if prior TBI, craniospinal XRT or if >= 50% radiation of pelvis; at least 42 days must have elapsed if other substantial BM radiation
    • Stem cell infusion without TBI: no evidence of active graft vs. host disease and at least 84 days must have elapsed after transplant and >= 42 days for autologous stem cell infusion after iodine (I)131-MIBG therapy
    • Patients must not have received prior therapy with crizotinib
    • Prior anthracycline dose: patients with a total lifetime cumulative anthracycline dose of > 650 mg/m^2 at the time of enrollment are not eligible for Part B of the study
  • For patients with solid tumors or ALCL without known bone marrow involvement:

    • Peripheral absolute neutrophil count (ANC) >= 1000/mm^3
    • 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; if dose-limiting hematologic toxicity is observed, all subsequent patients enrolled must be evaluable for hematologic toxicity
  • 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: 0.6 mg/dL
    • Age 2 to < 6 years: 0.8 mg/dL
    • Age 6 to < 10 years: 1 mg/dL
    • Age 10 to < 13 years: 1.2 mg/dL
    • Age 13 to < 16 years: 1.5 mg/dL (males) and 1.4 mg/dL (females)
    • Age >= 16 years: 1.7 mg/dL (males) and 1.4 mg/dL (females)
  • Bilirubin (sum of conjugated + unconjugated) =< 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
  • Corrected QT interval (QTc) =< 480 msec
  • For patients on Part B: shortening fraction of >= 27% by echocardiogram or ejection fraction of >= 50% by gated radionuclide study
  • 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
  • Part C: Patients must have a body surface area (BSA) >= 1.07 m^2 at the time of study enrollment
  • Tumor tissue must be sent; if tumor tissue is unavailable, the study chair must be notified prior to enrollment

Exclusion Criteria:

  • Pregnant or breast-feeding women will not be entered on this study; 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 during treatment and for 3 months after stopping 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
  • 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 chronically receiving medications known to be metabolized by cytochrome P 450, family 3, subfamily A, polypeptide 4 (CYP3A4) and with narrow therapeutic indices including pimozide, aripiprazole, triazolam, ergotamine and halofantrine are not eligible; the topical use of these medications (if applicable) is allowed
  • Patients chronically receiving drugs that are known potent CYP3A4 inhibitors within 7 days prior to study enrollment, including but not limited to ketoconazole, itraconazole, miconazole, clarithromycin, erythromycin, ritonavir, indinavir, nelfinavir, saquinavir, amprenavir, delavirdine, nefazodone, diltiazem, verapamil, and grapefruit juice are not eligible; the topical use of these medications (if applicable), e.g. 2% ketoconazole cream, is allowed
  • Patients chronically receiving drugs that are known potent CYP3A4 inducers within 12 days prior to study enrollment, including but not limited to carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, tipranavir, ritonavir, and St. John?s wort are not eligible; the topical use of these medications (if applicable) is allowed
  • Patients who have an uncontrolled infection are not eligible
  • Patients who have received a prior solid organ transplantation are not eligible
  • Patients who have a primary or metastatic CNS tumor at the time of study enrollment are not eligible; a prior history of metastatic CNS tumor is allowed as long as there is no evidence of CNS disease at study enrollment
  • 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
  • Parts A and B: Patients who are able to swallow liquid or use a nasogastric or gastrostomy (G) tube are eligible
  • Part C: Patients must be able to swallow intact capsules

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): NCT01606878


  Show 23 Study Locations
Sponsors and Collaborators
Children's Oncology Group
National Cancer Institute (NCI)
Investigators
Layout table for investigator information
Principal Investigator: Emily Greengard COG Phase I Consortium

Layout table for additonal information
Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT01606878     History of Changes
Other Study ID Numbers: ADVL1212
NCI-2012-01968 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
CDR0000734059
ADVL1212
ADVL1212 ( Other Identifier: COG Phase I Consortium )
ADVL1212 ( Other Identifier: CTEP )
UM1CA097452 ( U.S. NIH Grant/Contract )
First Posted: May 28, 2012    Key Record Dates
Last Update Posted: February 26, 2019
Last Verified: January 2019

Keywords provided by Children's Oncology Group:
Crizotinib
Chemotherapy
Solid Tumors
Anaplastic Large Cell Lymphoma

Additional relevant MeSH terms:
Layout table for MeSH terms
Lymphoma
Lymphoma, Non-Hodgkin
Neuroblastoma
Lymphoma, Large-Cell, Anaplastic
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Neuroectodermal Tumors, Primitive, Peripheral
Neuroectodermal Tumors, Primitive
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Lymphoma, T-Cell
Cyclophosphamide
Doxorubicin
Liposomal doxorubicin
Vincristine
Topotecan
Crizotinib
Dexrazoxane
Razoxane
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents