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Tailored Prednisone Reduction in Preventing Hyperglycemia in Participants With B-Cell Non-Hodgkin Lymphoma Receiving Combination Chemotherapy Treatment

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ClinicalTrials.gov Identifier: NCT03505762
Recruitment Status : Recruiting
First Posted : April 23, 2018
Last Update Posted : September 20, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Wake Forest University Health Sciences

Brief Summary:
This phase II trial studies how well tailored prednisone reduction works in preventing hyperglycemia in participants with B-cell non-Hodgkin lymphoma receiving combination chemotherapy treatment. Drugs used in chemotherapy, such as rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate and prednisone, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Reductions in prednisone dose may lower blood sugar levels.

Condition or disease Intervention/treatment Phase
B-Cell Non-Hodgkin Lymphoma Drug: Cyclophosphamide Drug: Doxorubicin Hydrochloride Other: Laboratory Biomarker Analysis Drug: Prednisone Other: Quality-of-Life Assessment Other: Questionnaire Administration Biological: Rituximab Drug: Vincristine Sulfate Phase 2

Detailed Description:

PRIMARY OBJECTIVES:

I. To compare the cumulative incidence of hyperglycemia after 3 cycles of treatment between standard or tailored rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate and prednisone (R-CHOP) chemotherapy.

SECONDARY OBJECTIVES:

I. To compare the cumulative incidence of hyperglycemia after 6 cycles of treatment and at 6 months post-treatment between standard or tailored R-CHOP chemotherapy.

II. To compare response rates after 6 cycles of treatment as measured by Cheson's criteria between standard or tailored R-CHOP chemotherapy.

III. To compare cumulative rates of grade III or higher adverse events using Common Terminology Criteria for Adverse Events (CTCAE) criteria between standard or tailored R-CHOP chemotherapy from cycle 1 through cycle 6.

IV. To compare severity of prednisone related adverse events using the Patient Reported Outcome (PRO)-CTCAE form between standard or tailored R-CHOP chemotherapy from cycle 1 through cycle 6.

V. To compare health related quality of life (HRQOL) between standard or tailored R-CHOP chemotherapy at baseline, cycle 4 day 1 and after cycle 6.

EXPLORATORY OBJECTIVES:

I. To evaluate the alternative glucose measures of fasting blood glucose (FBG), hemoglobin A1c (HbA1c), fasting insulin and fructosamine to estimate hyperglycemia.

II. To compare health related quality of life (HRQOL) in those with and without hyperglycemia after 3 cycles, 6 cycles, and 6 months post R-CHOP chemotherapy.

III. To compare glycemic variability between the standard and tailored prednisone arms at day 1 of each cycle IV. To determine the ability of patients in the standard or tailored prednisone R-CHOP groups to complete all six cycles of chemotherapy.

OUTLINE: Participants are randomized to 1 of 2 arms.

ARM I: Participants receive rituximab intravenously (IV), vincristine sulfate IV, doxorubicin hydrochloride IV, and cyclophosphamide IV on day 1. Participants also receive tailored prednisone dose orally (PO) once daily (QD) on days 1-5. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

ARM II: Participants receive rituximab, vincristine sulfate doxorubicin hydrochloride, and cyclophosphamide as in Arm I. Participants also receive usual care prednisone dose PO QD on days 1-5. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, participants are followed up for 30 days, then up to 6 months.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized Phase II Pilot of Tailored Prednisone Reduction Versus Usual Care for the Treatment of Hyperglycemia During R-CHOP Chemotherapy
Actual Study Start Date : July 19, 2018
Estimated Primary Completion Date : June 2022
Estimated Study Completion Date : June 2024

Resource links provided by the National Library of Medicine

Drug Information available for: Prednisone

Arm Intervention/treatment
Experimental: Arm I (tailored prednisone dose)
Participants receive rituximab IV, vincristine sulfate IV, doxorubicin hydrochloride IV, and cyclophosphamide IV on day 1. Participants also receive tailored prednisone dose PO QD on days 1-5. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
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

Other: Laboratory Biomarker Analysis
Correlative studies

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

Other: Quality-of-Life Assessment
Ancillary correlative
Other Name: Quality of Life Assessment

Other: Questionnaire Administration
Ancillary studies

Biological: Rituximab
Given IV
Other Names:
  • ABP 798
  • BI 695500
  • C2B8 Monoclonal Antibody
  • Chimeric Anti-CD20 Antibody
  • CT-P10
  • IDEC-102
  • IDEC-C2B8
  • IDEC-C2B8 Monoclonal Antibody
  • MabThera
  • Monoclonal Antibody IDEC-C2B8
  • PF-05280586
  • Rituxan
  • Rituximab Biosimilar ABP 798
  • Rituximab Biosimilar BI 695500
  • Rituximab Biosimilar CT-P10
  • Rituximab Biosimilar GB241
  • Rituximab Biosimilar IBI301
  • Rituximab Biosimilar PF-05280586
  • Rituximab Biosimilar RTXM83
  • Rituximab Biosimilar SAIT101
  • RTXM83

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

Active Comparator: Arm II (usual care prednisone dose)
Participants receive rituximab, vincristine sulfate doxorubicin hydrochloride, and cyclophosphamide as in Arm I. Participants also receive usual care prednisone dose PO QD on days 1-5. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
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

Other: Laboratory Biomarker Analysis
Correlative studies

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

Other: Quality-of-Life Assessment
Ancillary correlative
Other Name: Quality of Life Assessment

Other: Questionnaire Administration
Ancillary studies

Biological: Rituximab
Given IV
Other Names:
  • ABP 798
  • BI 695500
  • C2B8 Monoclonal Antibody
  • Chimeric Anti-CD20 Antibody
  • CT-P10
  • IDEC-102
  • IDEC-C2B8
  • IDEC-C2B8 Monoclonal Antibody
  • MabThera
  • Monoclonal Antibody IDEC-C2B8
  • PF-05280586
  • Rituxan
  • Rituximab Biosimilar ABP 798
  • Rituximab Biosimilar BI 695500
  • Rituximab Biosimilar CT-P10
  • Rituximab Biosimilar GB241
  • Rituximab Biosimilar IBI301
  • Rituximab Biosimilar PF-05280586
  • Rituximab Biosimilar RTXM83
  • Rituximab Biosimilar SAIT101
  • RTXM83

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




Primary Outcome Measures :
  1. Cumulative incidence of hyperglycemia of standard or tailored rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate and prednisone (R-CHOP) [ Time Frame: After course 3 (63 days) ]
    Will use the Kaplan Meier method to estimate the cumulative incidence of hyperglycemia, and the log-rank test to compare hyperglycemia incidence by arm after 3 cycles of R-CHOP chemotherapy.


Secondary Outcome Measures :
  1. Cumulative incidence of hyperglycemia of standard or tailored R-CHOP [ Time Frame: Baseline up to 6 months ]
    Will use the Kaplan Meier method to estimate the cumulative incidence of hyperglycemia, and the log-rank test to compare hyperglycemia incidence by arm after 6 cycles and after 6 months of R-CHOP chemotherapy.

  2. Response rates of standard or tailored R-CHOP as measured by Cheson's criteria [ Time Frame: After of course 6 (126 days) ]
    Will use a Fisher's exact test to compare response rates after 6 cycles of R-CHOP by arm.

  3. Rates of grade III or higher adverse events using Common Terminology Criteria for Adverse Events (CTCAE) criteria from standard or tailored R-CHOP [ Time Frame: Up to 6 months ]
    Will compare the rates of the incidence of grade III and higher events by arm of R-CHOP for each cycle using Fisher's exact tests.

  4. Severity of prednisone related adverse events using the Patient Reported Outcome (PRO)-CTCAE [ Time Frame: Up to course 6 (126 days) ]
    Will compare the scoring of PRO-CTCAE assessments by arm of R-CHOP using two group t-tests at each time point of interest.

  5. Health related quality of life (HRQOL) scores [ Time Frame: Up to 6 months ]
    Evaluated using the Functional Assessment of Cancer Therapy (FACT)-Lymphoma, FACT Gynecologic Oncology Group-Neurotoxicity additional concerns and Patient-Reported Outcomes Measurement Information System 29. Will compare the HRQOL measures between arms receiving R-CHOP chemotherapy using two group t-tests at each time point of interest.


Other Outcome Measures:
  1. Fasting blood glucose (FBG) levels [ Time Frame: Up to 6 months ]
    Will examine glucose variability over time in FBG using linear mixed effects models to model between and with-person variation in glucose.

  2. Hemoglobin A1C (HbA1c) levels [ Time Frame: Up to 6 months ]
    Will examine glucose variability over time in HbA1c using linear mixed effects models to model between and with-person variation in glucose.

  3. Fasting insulin [ Time Frame: Up to 6 months ]
    Will examine glucose variability over time in fasting insulin using linear mixed effects models to model between and with-person variation in glucose.

  4. Fructosamine levels [ Time Frame: Up to 6 months ]
    Will examine glucose variability over time in fructosamine using linear mixed effects models to model between and with-person variation in glucose.

  5. HRQOL scores in those with and without hyperglycemia [ Time Frame: Up to 6 months ]
    Will compare quality of life between the those who are hyperglycemic and those that are not at cycle 3, cycle 6, and 12 months using a mixed model analysis covariance (ANCOVA) with adjustment for baseline quality of life.

  6. Glycemic variability [ Time Frame: Up to 6 months ]
    To compare glycemic variability between the arms, will model variability using mixed effect models of FBG and random blood glucose over time, allowing for differing within-person variance by arm as well as fitting a model with pooled variance and any characteristics that differ between the groups. Will use likelihood ratio tests to compare if there is greater variability in the tailored versus standard arms by comparing the pooled variance model to the model that allows the within-person variation to vary by arm.

  7. Percentage of patients in the standard and tailored prednisone R-CHOP arms who complete all six cycles of chemotherapy [ Time Frame: End of course 6 (126 days) ]
    Will compare the proportion of participants by arm using Fisher's exact test.



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:

  • Diagnosis of B cell non-Hodgkin lymphoma confirmed by World Health Organization (WHO) criteria
  • Planned treatment with R-CHOP chemotherapy
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 3
  • Life expectancy of greater than 3 months with chemotherapy
  • Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
  • Ability to understand and the willingness to sign an Institutional Review Board (IRB)-approved informed consent document (either directly or via a legally authorized representative)

Exclusion Criteria:

  • Uncontrolled human immunodeficiency virus (HIV), CD4 count < 50
  • Diagnosis of primary central nervous system (CNS) lymphoma
  • Unable to receive R-CHOP chemotherapy
  • History of severe (i.e. anaphylactic) allergic reactions attributed to compounds of similar chemical or biologic composition to glucocorticoids and other component of R-
  • Uncontrolled intercurrent illness including, but not limited to ongoing or active infection not controlled with antibiotics, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia that cannot be rate controlled with medications, or psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with these agents

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): NCT03505762


Locations
Layout table for location information
United States, North Carolina
Wake Forest University Health Sciences Recruiting
Winston-Salem, North Carolina, United States, 27157
Contact: Brittany S. Mabe, RN    336-716-5440    bmabe@wakehealth.edu   
Principal Investigator: Rakhee Vaidya         
Sponsors and Collaborators
Wake Forest University Health Sciences
National Cancer Institute (NCI)
Investigators
Layout table for investigator information
Principal Investigator: Rakhee Vaidya Wake Forest University Health Sciences

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Responsible Party: Wake Forest University Health Sciences
ClinicalTrials.gov Identifier: NCT03505762     History of Changes
Other Study ID Numbers: IRB00050108
NCI-2018-00585 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
CCCWFU 98317 ( Other Identifier: Wake Forest University Health Sciences )
P30CA012197 ( U.S. NIH Grant/Contract )
First Posted: April 23, 2018    Key Record Dates
Last Update Posted: September 20, 2019
Last Verified: September 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, B-Cell
Hyperglycemia
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Glucose Metabolism Disorders
Metabolic Diseases
Prednisone
Cortisone
Cyclophosphamide
Rituximab
Doxorubicin
Liposomal doxorubicin
Vincristine
Antineoplastic Agents, Immunological
Antibodies
Immunoglobulins
Antibodies, Monoclonal
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action