Immunotherapy (Nivolumab or Brentuximab Vedotin) Plus Combination Chemotherapy in Treating Patients With Newly Diagnosed Stage III-IV Classic Hodgkin Lymphoma

  • STATUS
    Recruiting
  • End date
    Mar 1, 2024
  • participants needed
    987
  • sponsor
    National Cancer Institute (NCI)
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Updated on 30 June 2022
See if I qualify
ct scan
estimated creatinine clearance
cancer
corticosteroids
hysterectomy
lymphoma
immunosuppressive
monoclonal antibodies
prednisone
human immunodeficiency virus
measurable disease
hepatitis
cell transplantation
gilbert's syndrome
doxorubicin
combination chemotherapy
tumor cells
positron emission tomography
nivolumab
alopecia
pegfilgrastim
dacarbazine
vinblastine
topical steroids
hypothyroidism
positron emission tomography/computed tomography
brentuximab
classical hodgkin lymphoma
mixed cellularity hodgkin lymphoma

Summary

This phase III trial compares immunotherapy drugs (nivolumab or brentuximab vedotin) when given with combination chemotherapy in treating patients with newly diagnosed stage III or IV classic Hodgkin lymphoma. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Brentuximab vedotin is a monoclonal antibody, brentuximab, linked to a toxic agent called vedotin. Brentuximab attaches to cancer cells in a targeted way and delivers vedotin to kill them. Chemotherapy drugs, such as doxorubicin, vinblastine, and dacarbazine, 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. The addition of nivolumab or brentuximab vedotin to combination chemotherapy may shrink the cancer or extend the time without disease symptoms coming back.

Description

PRIMARY OBJECTIVE:

I. To compare the progression-free survival (PFS) in patients with newly diagnosed advanced stage classical Hodgkin lymphoma randomized to N-AVD (nivolumab, doxorubicin hydrochloride [doxorubicin], vinblastine sulfate [vinblastine], dacarbazine) versus that obtained with BV-AVD (brentuximab vedotin, doxorubicin, vinblastine, dacarbazine).

SECONDARY OBJECTIVES:

I. To compare overall survival (OS) in patients randomized to N-AVD versus BV-AVD.

II. To compare event-free survival (EFS) in patients randomized to N-AVD versus BV-AVD.

III. To compare the metabolic complete response (CR) rate at the end of treatment in patients randomized to N-AVD versus BV-AVD.

IV. To compare the physician-reported treatment-related adverse event rates between arms stratified by age groups.

V. To compare patient-reported symptoms using selected Patient Reported Outcome Common Toxicity Criteria for Adverse Events (PRO-CTCAE) items between arms stratified by age groups.

VI. To compare the safety and tolerability of N-AVD versus that of BV-AVD.

QUALITY OF LIFE OBJECTIVE:

I. To compare between arms patient-reported fatigue, neuropathy and health-related quality of life over time (baseline, beginning of cycle 3, 4-8 weeks after the last dose of protocol therapy [following last dose of study drug or radiation therapy, whichever is later], and 1 and 3 years after randomization) using the Patient Reported Outcomes Measurement Information System (PROMIS)-Fatigue, the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx), and the PROMIS Global, respectively.

BANKING OBJECTIVES:

I. To bank specimens for future correlative studies. II. To bank positron emission tomography (PET)-computed tomography (CT) images for future correlative studies.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive doxorubicin hydrochloride intravenously (IV), vinblastine sulfate IV, dacarbazine IV, and nivolumab IV over 30 minutes on days 1 and 15. Patients may receive pegfilgrastim subcutaneously (SC) on days 2 and 16, or filgrastim SC or IV on days 6-10 and 21-25. Treatment repeats every 28 days for 6 cycles in the absence of disease progression or unacceptable toxicity. After completion of cycle 6, patients may receive radiation therapy 5 days per week for approximately 4 weeks at the discretion of the treating physician.

ARM II: Patients receive doxorubicin hydrochloride IV, vinblastine sulfate IV, dacarbazine IV, and brentuximab vedotin IV over 30 minutes on days 1 and 15. Patients may receive pegfilgrastim SC on days 2 and 16, or filgrastim SC or IV on days 6-10 and 21-25. Treatment repeats every 28 days for 6 cycles in the absence of disease progression or unacceptable toxicity. After completion of cycle 6, patients may receive radiation therapy 5 days per week for approximately 4 weeks at the discretion of the treating physician.

After completion of study treatment and prior to disease progression, patients are followed up every 3 months for the first year, every 6 months for years 2 and 3, then annually until 10 years after registration. Patients are followed up at the time of progression and then annually until 10 years after registration. Patients who receive radiation therapy are followed up at 8-12 weeks after completion of radiation therapy.

Details
Condition Ann Arbor Stage III Hodgkin Lymphoma, Ann Arbor Stage III Lymphocyte-Depleted Classic Hodgkin Lymphoma, Ann Arbor Stage III Mixed Cellularity Classic Hodgkin Lymphoma, Ann Arbor Stage III Nodular Sclerosis Classic Hodgkin Lymphoma, Ann Arbor Stage IIIA Hodgkin Lymphoma, Ann Arbor Stage IIIB Hodgkin Lymphoma, Ann Arbor Stage IV Hodgkin Lymphoma, Ann Arbor Stage IV Lymphocyte-Depleted Classic Hodgkin Lymphoma, Ann Arbor Stage IV Mixed Cellularity Classic Hodgkin Lymphoma, Ann Arbor Stage IV Nodular Sclerosis Classic Hodgkin Lymphoma, Ann Arbor Stage IVA Hodgkin Lymphoma, Ann Arbor Stage IVB Hodgkin Lymphoma, Classic Hodgkin Lymphoma, Lymphocyte-Rich Classic Hodgkin Lymphoma
Treatment radiation therapy, questionnaire administration, filgrastim, quality-of-life assessment, doxorubicin hydrochloride, doxorubicin, Nivolumab, pegfilgrastim, dacarbazine, vinblastine sulfate, brentuximab vedotin, Vinblastine
Clinical Study IdentifierNCT03907488
SponsorNational Cancer Institute (NCI)
Last Modified on30 June 2022

Eligibility

 Yes No Not Sure

Inclusion Criteria

All patients must have histologically confirmed newly diagnosed, previously untreated stage III or IV classical Hodgkin lymphoma (nodular sclerosing, mixed cellularity, lymphocyte-rich, or lymphocyte-depleted, or not otherwise specified [NOS]). Nodular lymphocyte predominant Hodgkin lymphoma is not eligible
Patients must have bidimensionally measurable disease (at least one lesion with longest diameter >= 1.5 cm) documented on the Lymphoma Baseline Tumor Assessment Form in Rave
Patients must have a whole body or limited whole body PET-CT scan performed within 42 days prior to registration. (A contrast-enhanced [diagnostic] CT, MRI or MR-PET is acceptable in event that PET-CT is contra-indicated, however if it is later possible to administer a PET-CT, then PET-CT is strongly preferred for the interim scan (after cycle 2) (if performed) and the EOT assessment. Otherwise, if PET-CT is not subsequently possible, then the same modality as baseline must be used throughout the trial.) NOTE: All images from PET-CT, CT, MRI or MR-PET scans performed as standard of care to assess disease (within 42 days prior to registration) must be submitted and associated radiology reports must be submitted
Patients must not have received any prior chemotherapy, radiation, or antibody-based treatment for classical Hodgkin lymphoma. Steroid pre-treatment is permitted
Patients must not have had prior solid organ transplant
Patients must not have had prior allogeneic stem cell transplantation
Patients must not have received a live vaccine within 30 days prior to planned day 1 of protocol therapy (e.g. measles, mumps, rubella, varicella, yellow fever, rabies, Bacillus Calmette-Guerin [BCG], oral polio vaccine, and oral typhoid)
At registration, investigator must declare intent-to-treat with residual PET radiation therapy (residual PET RT- RPRT) to be administered after patient completes 6 cycles of therapy if, after end of treatment, the patient meets criteria specified for receiving RT). Patients will be stratified by investigator's intent-to-treat with residual PET RT
All pediatric patients (< 18 years of age) will be considered intent-to-treat with Residual PET RT at time of registration
Patients must have a performance status corresponding to Zubrod scores of 0, 1 or 2
Adults (age 18 or older): Creatinine clearance >= 30 mL/min, as estimated by the Cockcroft and Gault formula. The creatinine value used in the calculation must have been obtained within 28 days prior to registration. Estimated creatinine clearance is based on actual body weight
Use Lansky for patients =< 17 years of age. The conversion of the Lansky to
Eastern Cooperative Oncology Group (ECOG) scales is intended for National
Cancer Institute (NCI) reporting purposes only
Pediatric Patients (age 12-17), the following must have been obtained within 14 days prior
Age < 13 maximum serum creatinine: Male 1.2 mg/dL; Female 1.2 mg/dL
to registration
Age 13 to < 16 maximum serum creatinine: Male 1.5 mg/dL; Female 1.4 mg/dL
Measured or calculated creatinine clearance or radioisotope glomerular filtration rate
Age 16-17 maximum serum creatinine: Male 1.7 mg/dL; Female 1.4 mg/dL
(GFR) >= 70 ml/min/1.73 m^2, or
Serum creatinine =< 1.5 x institutional upper limit of normal (IULN), or a serum
creatinine (SCr) based on age/gender as follows
Total bilirubin =< 2 x IULN (must be documented within 28 days prior to
registration for adults [age 18 or older]; must be documented within 14 days
prior to registration for pediatric patients [age 12-17])
Unless due to Gilbert's disease, lymphomatous involvement of liver or vanishing bile
Patients must not have any known central nervous system lymphoma
duct syndrome
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3 x IULN
Patients must not have had a diagnosis of inherited or acquired immunodeficiency
(must be documented within 28 days prior to registration for adults [age 18 or
older]; must be documented within 14 days prior to registration for pediatric
patients [age 12-17])
Patients with peripheral neuropathy must have < grade 2 at date of registration
Unless due to Gilbert's disease, lymphomatous involvement of liver or vanishing bile
duct syndrome
Patients must have an echocardiogram (ECHO), multigated acquisition (MUGA), or
functional cardiac imaging scan with a left ventricular ejection (LVEF) fraction
>= 50% or a shortening fraction of >= 27%. For all patients, the ECHO, MUGA, or
functional cardiac imaging scan must be performed within 42 days prior to
registration
Patients with known human immunodeficiency virus (HIV) infection must be
receiving anti-retroviral therapy and have an undetectable or unquantifiable
viral load at their most recent viral load test within 6 months prior to
registration
Patients must not have known active hepatitis B (HBV) or hepatitis C virus (HCV)
at date of registration. Patients with previously treated HBV or HCV that have an
undetectable viral load within 6 months prior to registration and no residual
hepatic impairment are eligible
Patients must not have a history of or active interstitial pneumonitis or
interstitial lung disease
Patients must not have any known uncontrolled intercurrent illness including, but
not limited to symptomatic congestive heart failure, unstable angina pectoris
hemodynamically unstable cardiac arrhythmia, or psychiatric illness/social
situations that would limit compliance with study requirements
Patients must not have a condition requiring systemic treatment with either
corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive
medications within 14 days prior to registration. Inhaled or topical steroids
and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted
in the absence of active autoimmune disease. Steroid use for the control of
Hodgkin lymphoma symptoms is allowable, but must be discontinued prior to cycle
day 1
Patients must not have active autoimmune disease that has required systemic
treatment in past 2 years (i.e., with use of disease modifying agents
immunosuppressive drugs, or corticosteroids with doses higher than prednisone 10
mg or equivalent). Autoimmune diseases include but are not limited to autoimmune
hepatitis, inflammatory bowel disease (including ulcerative colitis and Crohn's
disease), as well as symptomatic disease (e.g.: rheumatoid arthritis, systemic
progressive sclerosis [scleroderma], systemic lupus erythematosus, autoimmune
vasculitis [e.g., Wegener's granulomatosis]); central nervous system (CNS) or
motor neuropathy considered of autoimmune origin (e.g., Guillain-Barre syndrome
and myasthenia gravis, multiple sclerosis or glomerulonephritis). Vitiligo
alopecia, hypothyroidism on stable doses of thyroid replacement therapy
psoriasis not requiring systemic therapy within the past 2 years are permitted
No second prior malignancy is allowed except for adequately treated basal (or
squamous cell) skin cancer, any in situ cancer or other cancer for which the
patient has been disease free for two years
Females of childbearing potential must not be pregnant or nursing, and have a
negative pregnancy test within 28 days prior to registration. Women/men of
reproductive potential must have agreed to use an effective contraceptive method
while receiving study drug and for women until 6 months after receiving the last
dose of study drug or, for men, until 7 months after receiving the last dose of
study drug. A woman is considered to be of "reproductive potential" if she has
had menses at any time in the preceding 12 consecutive months. In addition to
routine contraceptive methods, "effective contraception" also includes
heterosexual celibacy and surgery intended to prevent pregnancy (or with a
side-effect of pregnancy prevention) defined as a hysterectomy, bilateral
oophorectomy or bilateral tubal ligation. However, if at any point a previously
celibate patient chooses to become heterosexually active during the time period
for use of contraceptive measures outlined in the protocol, he/she is responsible
for beginning contraceptive measures
Patients must have one formalin-fixed paraffin embedded (FFPE) diagnostic tumor
block or at least 1 diagnostic, 4-5 micron, hematoxylin and eosin (H&E) slide
collected prior to registration and available for submission
Patients must be offered participation in banking for planned translational
medicine and future research. With patient consent, any residuals from the
mandatory tissue submission will also be banked for future research
Patients who can complete Patient-Reported Outcome instruments in English
Spanish, or French must complete the PROMIS Fatigue, the FACT/GOG-Ntx, and the
PROMIS Global prior to registration
Patients who can complete Patient-Reported Outcome instruments in English
Spanish, or French must also agree to complete the PROMIS Fatigue, the
FACT/GOG-Ntx, the PROMIS Global, and the PRO-CTCAE (or Ped PRO-CTCAE) at the
scheduled on-study assessment timepoints
Patients must be informed of the investigational nature of this study and all
patients and/or their parents or legal guardians (for patients < 18 years of age)
must sign and give informed consent and assent (where appropriate) in accordance
with institutional and federal guidelines. For participants with impaired
decision-making capabilities, legally authorized representatives may sign and
give informed consent on behalf of study participants in accordance with
applicable federal, local, and Central Institutional Review Board Initiative
(CIRB) regulations
Note: As a part of the Oncology Patient Enrollment Network (OPEN) registration process
the treating institution's identity is provided in order to ensure that the current
(within 365 days) date of institutional review board approval for this study has been
entered in the system
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ct scan
estimated creatinine clearance
cancer
corticosteroids
hysterectomy
lymphoma
immunosuppressive
monoclonal antibodies
prednisone
human immunodeficiency virus
measurable disease
hepatitis
cell transplantation
gilbert's syndrome
doxorubicin
combination chemotherapy
tumor cells
positron emission tomography
nivolumab
alopecia
pegfilgrastim
dacarbazine
vinblastine
topical steroids
hypothyroidism
positron emission tomography/computed tomography
brentuximab
classical hodgkin lymphoma
mixed cellularity hodgkin lymphoma

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