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

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

View full results

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

46 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-04-29

Study Completion Date

2018-12-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Related Clinical Trials

Explore similar clinical trials based on study characteristics and research focus.

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

NCT00939770

Recurrent Childhood Anaplastic Large Cell Lymphoma Recurrent Malignant Solid Neoplasm Recurrent Neuroblastoma +3 more

COMPLETED PHASE1/PHASE2

High-Risk Neuroblastoma Chemotherapy Without G-CSF

NCT02786719

Neuroblastoma

COMPLETED NA

Oxaliplatin and Irinotecan in Treating Young Patients With Refractory Solid Tumors or Lymphomas

NCT00101270

Childhood Burkitt Lymphoma Childhood Central Nervous System Germ Cell Tumor Childhood Diffuse Large Cell Lymphoma +26 more

COMPLETED PHASE1

Comparing Two Different Myeloablation Therapies in Treating Young Patients Who Are Undergoing a Stem Cell Transplant for High-Risk Neuroblastoma

NCT00567567

Localized Resectable Neuroblastoma Localized Unresectable Neuroblastoma Recurrent Neuroblastoma +3 more

COMPLETED PHASE3

Response and Biology-Based Risk Factor-Guided Therapy in Treating Younger Patients With Non-high Risk Neuroblastoma

NCT02176967

Ganglioneuroblastoma Localized Resectable Neuroblastoma Localized Unresectable Neuroblastoma +1 more

ACTIVE_NOT_RECRUITING PHASE3

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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.

PART D: Patients receive crizotinib (microsphere 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.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Childhood Solid Neoplasm Recurrent Childhood Anaplastic Large Cell Lymphoma Recurrent Neuroblastoma

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

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)

Group Type EXPERIMENTAL

Crizotinib

Intervention Type DRUG

Given PO

Cyclophosphamide

Intervention Type DRUG

Given IV

Laboratory Biomarker Analysis

Intervention Type OTHER

Correlative studies

Pharmacological Study

Intervention Type OTHER

Correlative studies

Questionnaire Administration

Intervention Type OTHER

Ancillary studies

Topotecan Hydrochloride

Intervention Type DRUG

Given IV

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)

Group Type EXPERIMENTAL

Crizotinib

Intervention Type DRUG

Given PO

Dexrazoxane Hydrochloride

Intervention Type DRUG

Given IV

Doxorubicin Hydrochloride

Intervention Type DRUG

Given IV

Laboratory Biomarker Analysis

Intervention Type OTHER

Correlative studies

Pharmacological Study

Intervention Type OTHER

Correlative studies

Questionnaire Administration

Intervention Type OTHER

Ancillary studies

Vincristine Sulfate

Intervention Type DRUG

Given IV

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.

Group Type EXPERIMENTAL

Crizotinib

Intervention Type DRUG

Given PO

Cyclophosphamide

Intervention Type DRUG

Given IV

Laboratory Biomarker Analysis

Intervention Type OTHER

Correlative studies

Pharmacological Study

Intervention Type OTHER

Correlative studies

Questionnaire Administration

Intervention Type OTHER

Ancillary studies

Topotecan Hydrochloride

Intervention Type DRUG

Given IV

Part D (crizotinib, cyclophosphamide, topotecan hydrochloride)

Patients receive crizotinib (microsphere 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.

Group Type EXPERIMENTAL

Crizotinib

Intervention Type DRUG

Given PO

Cyclophosphamide

Intervention Type DRUG

Given IV

Laboratory Biomarker Analysis

Intervention Type OTHER

Correlative studies

Pharmacological Study

Intervention Type OTHER

Correlative studies

Questionnaire Administration

Intervention Type OTHER

Ancillary studies

Topotecan Hydrochloride

Intervention Type DRUG

Given IV

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Crizotinib

Given PO

Intervention Type DRUG

Cyclophosphamide

Given IV

Intervention Type DRUG

Dexrazoxane Hydrochloride

Given IV

Intervention Type DRUG

Doxorubicin Hydrochloride

Given IV

Intervention Type DRUG

Laboratory Biomarker Analysis

Correlative studies

Intervention Type OTHER

Pharmacological Study

Correlative studies

Intervention Type OTHER

Questionnaire Administration

Ancillary studies

Intervention Type OTHER

Topotecan Hydrochloride

Given IV

Intervention Type DRUG

Vincristine Sulfate

Given IV

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

MET Tyrosine Kinase Inhibitor PF-02341066 PF-02341066 PF-2341066 Xalkori (-)-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 Cardioxane Totect Zinecard 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 Hycamptamine Hycamtin SKF S-104864-A Topotecan HCl topotecan hydrochloride (oral) Kyocristine Leurocristine sulfate Leurocristine, sulfate Oncovin Vincasar Vincosid Vincrex Vincristine, sulfate

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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
* Patients 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
* Part D: Patients must have a body surface area (BSA) \>= 0.43 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 receiving PPIs and H2 blockers are not eligible for Part D
* 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
* Part D: Patients must be able to swallow liquid

Minimum Eligible Age

13 Months

Maximum Eligible Age

21 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Emily Greengard

Role: PRINCIPAL_INVESTIGATOR

COG Phase I Consortium

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Children's Hospital of Alabama

Birmingham, Alabama, United States

Site Status

Children's Hospital Los Angeles

Los Angeles, California, United States

Site Status

Children's Hospital of Orange County

Orange, California, United States

Site Status

UCSF Medical Center-Parnassus

San Francisco, California, United States

Site Status

UCSF Medical Center-Mission Bay

San Francisco, California, United States

Site Status

Children's Hospital Colorado

Aurora, Colorado, United States

Site Status

Children's National Medical Center

Washington D.C., District of Columbia, United States

Site Status

Children's Healthcare of Atlanta - Egleston

Atlanta, Georgia, United States

Site Status

Lurie Children's Hospital-Chicago

Chicago, Illinois, United States

Site Status

Riley Hospital for Children

Indianapolis, Indiana, United States

Site Status

C S Mott Children's Hospital

Ann Arbor, Michigan, United States

Site Status

University of Minnesota/Masonic Cancer Center

Minneapolis, Minnesota, United States

Site Status

Washington University School of Medicine

St Louis, Missouri, United States

Site Status

Columbia University/Herbert Irving Cancer Center

New York, New York, United States

Site Status

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Site Status

Oregon Health and Science University

Portland, Oregon, United States

Site Status

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Site Status

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, United States

Site Status

St. Jude Children's Research Hospital

Memphis, Tennessee, United States

Site Status

Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center

Houston, Texas, United States

Site Status

Seattle Children's Hospital

Seattle, Washington, United States

Site Status

Children's Hospital of Wisconsin

Milwaukee, Wisconsin, United States

Site Status

Hospital for Sick Children

Toronto, Ontario, Canada

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States Canada

References

Explore related publications, articles, or registry entries linked to this study.

Greengard E, Mosse YP, Liu X, Minard CG, Reid JM, Voss S, Wilner K, Fox E, Balis F, Blaney SM, Adamson PC, Weigel BJ. Safety, tolerability and pharmacokinetics of crizotinib in combination with cytotoxic chemotherapy for pediatric patients with refractory solid tumors or anaplastic large cell lymphoma (ALCL): a Children's Oncology Group phase 1 consortium study (ADVL1212). Cancer Chemother Pharmacol. 2020 Dec;86(6):829-840. doi: 10.1007/s00280-020-04171-4. Epub 2020 Oct 23.

Reference Type DERIVED

PMID: 33095287 (View on PubMed)

Provided Documents

Download supplemental materials such as informed consent forms, study protocols, or participant manuals.

Document Type: Study Protocol and Statistical Analysis Plan

View Document