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Trial record 3 of 8 for:    "Enteropathy-Associated T-Cell Lymphoma" | "Antineoplastic Agents, Phytogenic"

Combination Chemotherapy and Lenalidomide in Treating Patients With Newly Diagnosed Stage II-IV Peripheral T-cell Non-Hodgkin's Lymphoma

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ClinicalTrials.gov Identifier: NCT02561273
Recruitment Status : Active, not recruiting
First Posted : September 28, 2015
Last Update Posted : September 10, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Matthew Lunning, DO, University of Nebraska

Brief Summary:
This phase I/II trial studies the side effects and best dose of lenalidomide when given together with combination chemotherapy and to see how well they work in treating patients with newly diagnosed stage II-IV peripheral T-cell non-Hodgkin's lymphoma. Drugs used in chemotherapy, such as cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and etoposide, 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. Lenalidomide may stop the growth of peripheral T-cell non-Hodgkin's lymphoma by blocking the growth of new blood vessels necessary for cancer growth. Giving combination chemotherapy with lenalidomide may be a better treatment for peripheral T-cell non-Hodgkin's lymphoma.

Condition or disease Intervention/treatment Phase
Anaplastic Large Cell Lymphoma, ALK-Negative Anaplastic Large Cell Lymphoma, ALK-Positive Hepatosplenic T-Cell Lymphoma Peripheral T-Cell Lymphoma, Not Otherwise Specified Stage II Angioimmunoblastic T-cell Lymphoma Stage II Enteropathy-Associated T-Cell Lymphoma Stage III Angioimmunoblastic T-cell Lymphoma Stage III Enteropathy-Associated T-Cell Lymphoma Stage IV Angioimmunoblastic T-cell Lymphoma Stage IV Enteropathy-Associated T-Cell Lymphoma Procedure: Autologous Hematopoietic Stem Cell Transplantation Drug: Cyclophosphamide Drug: Doxorubicin Hydrochloride Drug: Etoposide Other: Laboratory Biomarker Analysis Drug: Lenalidomide Procedure: Peripheral Blood Stem Cell Transplantation Drug: Prednisone Drug: Vincristine Sulfate Phase 1 Phase 2

Detailed Description:

PRIMARY OBJECTIVES:

I. To assess the safety and efficacy of lenalidomide in combination with standard induction therapy (CHOEP- cyclophosphamide, doxorubicin [doxorubicin hydrochloride], etoposide, vincristine [vincristine sulfate] and prednisone) in patients with newly diagnosed stage II, III and IV peripheral T-cell lymphoma not otherwise specified (NOS), anaplastic large cell lymphoma (anaplastic lymphoma receptor tyrosine kinase [ALK] negative) (ALK positive if International Prognostic Index [IPI] 3, 4, or 5), angioimmunoblastic T-cell lymphoma, enteropathy associated T-cell lymphoma or hepatosplenic gamma delta T-cell lymphoma.

II. To establish the maximum tolerated dose of lenalidomide in combination with CHOEP chemotherapy. (Phase I) III. To assess the efficacy (complete response rate) of this combination. (Phase II)

SECONDARY OBJECTIVES:

I. To evaluate overall response rate (complete response [CR] + partial response [PR]) of the combination of lenalidomide and CHOEP chemotherapy.

II. To evaluate the safety and tolerability of the regimen. III. To assess the 2 year progression free survival (PFS) and overall survival (OS) using this regimen.

OUTLINE: This is a phase I, dose-escalation study of lenalidomide, followed by a phase II study.

Patients receive cyclophosphamide intravenously (IV), doxorubicin hydrochloride IV and vincristine sulfate IV on day 1, etoposide IV over 30-60 minutes on days 1-3, prednisone orally (PO) on days 1-5, and lenalidomide PO on days 1-10. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients responding after 6 courses of treatment may then undergo an autologous stem cell transplant or receive maintenance lenalidomide at the discretion of the physician or patient choice as follows:

TRANSPLANT: Patients undergo autologous stem cell transplant per standard of care.

MAINTENANCE LENALIDOMIDE: Patients receive lenalidomide PO on days 1-21. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 1 year.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 54 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I/II Trial of CHOEP Chemotherapy Plus Lenalidomide as Front Line Therapy for Patients With Stage II, III and IV Peripheral T-Cell Non-Hodgkin's Lymphoma
Study Start Date : October 2015
Estimated Primary Completion Date : October 2020
Estimated Study Completion Date : October 2021


Arm Intervention/treatment
Experimental: Treatment (combination chemotherapy, lenalidomide)

Patients receive cyclophosphamide IV, doxorubicin hydrochloride IV and vincristine sulfate IV on day 1, etoposide IV over 30-60 minutes on days 1-3, prednisone PO on days 1-5, and lenalidomide PO on days 1-10. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients responding after 6 courses of treatment may then undergo an autologous stem cell transplant or receive maintenance lenalidomide at the discretion of the physician or patient choice as follows:

TRANSPLANT: Patients undergo autologous stem cell transplant per standard of care.

MAINTENANCE LENALIDOMIDE: Patients receive lenalidomide PO on days 1-21. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

Procedure: Autologous Hematopoietic Stem Cell Transplantation
Undergo autologous stem cell transplant
Other Name: Autologous Stem Cell Transplantation

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

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

Drug: Etoposide
Given IV
Other Names:
  • Demethyl Epipodophyllotoxin Ethylidine Glucoside
  • EPEG
  • Lastet
  • Toposar
  • Vepesid
  • VP 16-213
  • VP-16
  • VP-16-213

Other: Laboratory Biomarker Analysis
Correlative studies

Drug: Lenalidomide
Given PO
Other Names:
  • CC-5013
  • CC5013
  • CDC 501
  • Revlimid

Procedure: Peripheral Blood Stem Cell Transplantation
Undergo peripheral blood stem cell transplant
Other Names:
  • PBPC transplantation
  • Peripheral Blood Progenitor Cell Transplantation
  • Peripheral Stem Cell Support
  • Peripheral Stem Cell Transplant
  • Peripheral Stem Cell Transplantation

Drug: Prednisone
Given PO
Other Names:
  • .delta.1-Cortisone
  • 1, 2-Dehydrocortisone
  • Adasone
  • Cortancyl
  • Dacortin
  • DeCortin
  • Decortisyl
  • Decorton
  • Delta 1-Cortisone
  • Delta-Dome
  • Deltacortene
  • Deltacortisone
  • Deltadehydrocortisone
  • Deltasone
  • Deltison
  • Deltra
  • Econosone
  • Lisacort
  • Meprosona-F
  • Metacortandracin
  • Meticorten
  • Ofisolona
  • Orasone
  • Panafcort
  • Panasol-S
  • Paracort
  • PRED
  • Predicor
  • Predicorten
  • Prednicen-M
  • Prednicort
  • Prednidib
  • Prednilonga
  • Predniment
  • Prednisonum
  • Prednitone
  • Promifen
  • Servisone
  • SK-Prednisone

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




Primary Outcome Measures :
  1. Complete response rate (Phase II) [ Time Frame: Up to the completion of course 6 (18 weeks) ]
    A success is defined to be an objective status of CR after completion of 6 cycles of treatment. The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. A 95% confidence interval for the true overall CR rate will be calculated according to the method of Duffy and Santner.

  2. Incidence of toxicity graded according to Common Toxicity Criteria (CTC) (Phase I) [ Time Frame: Up to 1 year ]
    Non-hematologic toxicities will be evaluated via the ordinal CTC standard toxicity grading. Hematologic toxicity measures of thrombocytopenia, neutropenia, and leukopenia will be assessed using continuous variables as the outcome measures (primarily nadir) as well as categorization via CTC standard toxicity grading. Overall toxicity incidence as well as toxicity profiles by dose level and patient will be explored and summarized. Frequency distributions, graphical techniques and other descriptive measures will form the basis of these analyses.

  3. Maximum tolerated dose of lenalidomide and CHOEP, defined as the dose level below the lowest dose that induces dose-limiting toxicity in at least one-third of patients (at least 2 of a maximum of 6 new patients) (Phase I) [ Time Frame: 21 days ]
  4. Overall response rate [ Time Frame: Up to the completion of course 6 (18 weeks) ]
    The ORR will be estimated by the total number of patients who achieve a PR or CR at the end of six cycles of treatment divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for the true ORR will be calculated.


Secondary Outcome Measures :
  1. Incidence of toxicity graded according to CTC (Phase II) [ Time Frame: Up to 1 year ]
    The toxicity profile will be further assessed based on phase II patients. Overall toxicity incidence as well as toxicity profiles by dose level and patient will be explored and summarized. Frequency distributions, graphical techniques and other descriptive measures will form the basis of these analyses.

  2. Overall survival [ Time Frame: Time from registration to death due to any cause, assessed up to 1 year ]
    The distribution of overall survival will be estimated using the method of Kaplan-Meier.

  3. Progression-free survival [ Time Frame: Time from registration to progression or death due to any cause, assessed up to 2 years ]
    The distribution of PFS will be estimated using the method of Kaplan-Meier. The PFS rate at 2 years will be estimated. A 2-year PFS rate of 60% will be considered of interest.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically confirmed new diagnosis of stage II, III and IV peripheral T-cell non-Hodgkin's lymphoma not otherwise specified (NOS), anaplastic large cell lymphoma (ALK negative) (ALK positive if IPI 3, 4, or 5), angioimmunoblastic T-cell lymphoma, enteropathy associated T-cell lymphoma, hepatosplenic gamma delta T-cell lymphoma
  • Pathology material: hematoxylin and eosin (H&E) stain and immunohistochemistry (IHC) slides or a representative formalin-fixed paraffin-embedded (FFPE) tissue block along with the pathology report from initial diagnosis, should be sent to be reviewed, and the diagnosis confirmed by Mayo Clinic department (retrospective diagnostic review: treatment may commence prior to the Mayo Clinic review)
  • No prior therapy with the exception of prior radiation therapy and/or prednisone alone, at the discretion of the investigator based on current diagnosis and clinical condition; this prednisone treatment will not count toward the 6 cycles of treatment given in the study
  • Expected survival duration of > 3 months
  • Karnofsky performance status > 70
  • Absolute neutrophil count (ANC) > 1000 cells/mm^3, unless cytopenias due to non-Hodgkin lymphoma (NHL) (i.e., bone marrow involvement or splenomegaly)
  • Platelet count > 100,000/uL or > 75,000/uL if bone marrow (BM) involvement or splenomegaly
  • Total bilirubin =< 1.5 x upper normal limit, or =< 3 x upper normal limit if documented hepatic involvement with lymphoma, or =< 5 x upper normal limit if history of Gilbert's disease
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x upper normal limit (=< 5 x upper normal limit if documented hepatic involvement with lymphoma)
  • Serum creatinine < 2.0 mg/dL or calculated creatinine clearance (CrCl) > 45 mL/min (Cockcroft-Gault)
  • Prothrombin time (PT) or international normalized ratio (INR), and partial thromboplastin time (PTT) =< 1.5 x upper limit of normal unless patient is receiving anticoagulants; if patient is on warfarin therapy, levels should be within therapeutic range
  • If currently not on anticoagulation medication, willing and able to take aspirin (81 or 325 mg) daily; if aspirin is contraindicated, the patient may be considered for the study if on therapeutic dose warfarin or low molecular weight heparin; patients unable to take any prophylaxis are not eligible
  • Patients with measurable disease; patients with non-measurable but evaluable disease may be eligible after discussion with the principal investigator (PI); baseline measurements and evaluations must be obtained within 6 weeks of registration to the study; abnormal positron emission tomography (PET)/computed tomography (CT) scans will not constitute evaluable disease, unless verified by CT scan or other appropriate imaging
  • Patients with measurable disease must have at least one objective measurable disease parameter; a clearly defined, bi-dimensionally measurable defect or mass measuring at least 1.5 cm in diameter on the CT portion of a PET/CT or CT scan or magnetic resonance imaging (MRI) (if appropriate) will constitute measurable disease; proof of lymphoma in the liver is required by a confirmation biopsy; skin lesions can be used as measurable disease provided bi-dimensional measurements are possible
  • All study participants must be registered into the mandatory Revlimid Risk Evaluation and Mitigation Strategy (REMS) program, and be willing and able to comply with the requirements of the REMS program
  • Women must not be pregnant or breast-feeding

    • Females of reproductive potential must adhere to the scheduled pregnancy testing as required in the Revlimid REMS program
    • All females of childbearing potential must have a blood test within 2 weeks prior to registration to rule out pregnancy
    • Pregnancy testing is not required for post-menopausal or surgically sterilized women
  • Male and female patients of reproductive potential must agree follow accepted birth control measures
  • Patient must be able to adhere to the study visit schedule and other protocol requirements
  • Patients must be willing to give written informed consent, and sign an institutionally approved consent form before performance of any study-related procedure not part of normal medical care as noted above; with the exception of 1 cycle of chemotherapy based on current diagnosis and clinical condition, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care
  • No serious disease or condition that, in the opinion of the investigator, would compromise the patient's ability to participate in the study

Exclusion Criteria:

  • Pregnant or breast feeding females
  • Known seropositive for or active viral infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV); patients who are seropositive ( i.e. hepatitis B core antibody positive; quantitative deoxyribonucleic acid [DNA] negative) are eligible with appropriate prophylaxis
  • Major surgery within 2 weeks of study drug administration
  • Prior malignancies within the past 3 years with exception of adequately treated basal cell, squamous cell skin cancer, or thyroid cancer; carcinoma in situ of the cervix or breast; prostate cancer of Gleason grade 6 or less with stable prostate-specific antigen (PSA) levels
  • Patients with a diagnosis of other peripheral T-cell lymphoma (PTCL) histologies other than those specified in the inclusion criteria
  • Contraindication to any of the required concomitant drugs or supportive treatments, including hypersensitivity to all anticoagulation and antiplatelet options, or antiviral drugs
  • Any other clinically significant medical disease or condition laboratory abnormality or psychiatric illness that, in the Investigator's opinion, may interfere with protocol adherence or a subject's ability to give informed consent
  • Known hypersensitivity to thalidomide or lenalidomide
  • The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide, lenalidomide or similar drugs
  • Ejection fraction of < 45% by either multi gated acquisition scan (MUGA) or echocardiogram (ECHO)

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): NCT02561273


Locations
Layout table for location information
United States, California
City of Hope Comprehensive Cancer Center
Duarte, California, United States, 91010
Stanford Cancer Institute
Palo Alto, California, United States, 94304
United States, Colorado
University of Colorado Cancer Center - Anschutz Cancer Pavilion
Aurora, Colorado, United States, 80045
United States, Georgia
Emory University/Winship Cancer Institute
Atlanta, Georgia, United States, 30322
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
United States, Missouri
Washington University School of Medicine
Saint Louis, Missouri, United States, 63110
United States, Nebraska
University of Nebraska Medical Center
Omaha, Nebraska, United States, 68198
United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10065
Sponsors and Collaborators
University of Nebraska
National Cancer Institute (NCI)
Investigators
Layout table for investigator information
Principal Investigator: Matthew Lunning University of Nebraska

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Responsible Party: Matthew Lunning, DO, Principal Investigator, University of Nebraska
ClinicalTrials.gov Identifier: NCT02561273     History of Changes
Other Study ID Numbers: 511-14
NCI-2015-00088 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
RV-CL-PTCL-PI-003858
511-14 ( Other Identifier: University of Nebraska Medical Center )
P30CA036727 ( U.S. NIH Grant/Contract )
First Posted: September 28, 2015    Key Record Dates
Last Update Posted: September 10, 2019
Last Verified: September 2019
Additional relevant MeSH terms:
Layout table for MeSH terms
Enteropathy-Associated T-Cell Lymphoma
Antineoplastic Agents, Phytogenic
Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, T-Cell
Lymphoma, Large-Cell, Anaplastic
Lymphoma, T-Cell, Peripheral
Intestinal Diseases
Immunoblastic Lymphadenopathy
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphadenopathy
Gastrointestinal Diseases
Digestive System Diseases
Prednisone
Cortisone
Cyclophosphamide
Doxorubicin
Liposomal doxorubicin
Lenalidomide
Etoposide
Etoposide phosphate
Vincristine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs