Combination Chemotherapy & Lenalidomide in Newly Diagnosed Stage II-IV Peripheral T-cell Non-Hodgkin's Lymphoma

NCT02561273 | Completed Phase 1 Results DMC FDA Drug

• 4 other identifiers: 0511-14-FBNCI-2015-00088RV-CL-PTCL-PI-003858P30CA036727
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 8

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.

Conditions

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

Outcome Measures

Primary Outcomes (4)

• Maximum Tolerated Dose (MTD) of Lenalidomide and CHOEP

  MTD is 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) within the first cycle of study treatment.

  21 days

• Number of Participants With Adverse Events Graded According to Common Toxicity Criteria (CTC) (Phase I)

  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.

  Up to 6 cycles of treatment (approximately 5 months)

• Complete Response Rate (Phase II)

  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.

  Up to the completion of course 6 (18 weeks)

• Overall Response Rate

  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.

  Up to the completion of course 6 (18 weeks)

Secondary Outcomes (3)

• Number of Participants With Adverse Events Graded According to CTC (Phase II)

  Up to 1 year

• Overall Survival

  Time from registration to death due to any cause, assessed up to 1 year

• Progression-free Survival

  Time from registration to progression or death due to any cause, assessed up to 2 years

Study Arms (1)

Treatment (combination chemotherapy, lenalidomide)

EXPERIMENTAL

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; Drug: Cyclophosphamide; Drug: Doxorubicin Hydrochloride; Drug: Etoposide; Other: Laboratory Biomarker Analysis; Drug: Lenalidomide; Procedure: Peripheral Blood Stem Cell Transplantation; Drug: Prednisone; Drug: Vincristine Sulfate

Interventions

Autologous Hematopoietic Stem Cell Transplantation PROCEDURE

Undergo autologous stem cell transplant

Also known as: Autologous Stem Cell Transplantation

Treatment (combination chemotherapy, lenalidomide)

Cyclophosphamide DRUG

Given IV

Also known as: (-)-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

Treatment (combination chemotherapy, lenalidomide)

Doxorubicin Hydrochloride DRUG

Given IV

Also known as: 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

Treatment (combination chemotherapy, lenalidomide)

Etoposide DRUG

Given IV

Also known as: Demethyl Epipodophyllotoxin Ethylidine Glucoside, EPEG, Lastet, Toposar, Vepesid, VP 16-213, VP-16, VP-16-213

Treatment (combination chemotherapy, lenalidomide)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (combination chemotherapy, lenalidomide)

Lenalidomide DRUG

Given PO

Also known as: CC-5013, CC5013, CDC 501, Revlimid

Treatment (combination chemotherapy, lenalidomide)

Peripheral Blood Stem Cell Transplantation PROCEDURE

Undergo peripheral blood stem cell transplant

Also known as: PBPC transplantation, Peripheral Blood Progenitor Cell Transplantation, Peripheral Stem Cell Support, Peripheral Stem Cell Transplant, Peripheral Stem Cell Transplantation

Treatment (combination chemotherapy, lenalidomide)

Prednisone DRUG

Given PO

Also known as: .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

Treatment (combination chemotherapy, lenalidomide)

Vincristine Sulfate DRUG

Given IV

Also known as: Kyocristine, Leurocristine Sulfate, Leurocristine, sulfate, Oncovin, Vincasar, Vincosid, Vincrex, Vincristine, sulfate

Treatment (combination chemotherapy, lenalidomide)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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)

Sponsors & Collaborators

• University of Nebraska: lead
• National Cancer Institute (NCI): collaborator

Study Sites (8)

City of Hope Comprehensive Cancer Center

Duarte, California, 91010, United States

Location

Stanford Cancer Institute

Palo Alto, California, 94304, United States

Location

University of Colorado Cancer Center, Anschutz Cancer Pavilion

Aurora, Colorado, 80045, United States

Location

Emory University/Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

MeSH Terms

Conditions

Lymphoma, Large-Cell, Anaplastic; Lymphoma, T-Cell; Immunoblastic Lymphadenopathy; Enteropathy-Associated T-Cell Lymphoma

Interventions

Cyclophosphamide; Doxorubicin; Etoposide; Lenalidomide; Peripheral Blood Stem Cell Transplantation; Prednisone; deltacortene; prednylidene; Vincristine

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphadenopathy

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Glucosides; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Hematopoietic Stem Cell Transplantation; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Indolizidines; Indolizines

Results Point of Contact

• Title: Matthew Lunning
• Organization: University of Nebraska Medical Center

mlunning@unmc.edu

402-559-7164

Study Officials

• Matthew A Lunning

  University of Nebraska

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 24, 2015
• First Posted: September 28, 2015
• Study Start: September 28, 2015
• Primary Completion: November 1, 2019
• Study Completion: November 1, 2020
• Last Updated: December 13, 2023
• Results First Posted: June 18, 2021

Record last verified: 2023-12

Locations

US (8)