Parsaclisib Plus the Standard Drug Therapy in Patients With Newly Diagnosed, High Risk Diffuse Large B-cell Lymphoma

  • STATUS
    Recruiting
  • End date
    May 15, 2027
  • participants needed
    44
  • sponsor
    Mayo Clinic
Updated on 16 June 2022
platelet count
cancer
cyclophosphamide
cytarabine
rituximab
absolute neutrophil count
vincristine
monoclonal antibodies
prednisone
measurable disease
direct bilirubin
etoposide
doxorubicin
neutrophil count
monoclonal antibody therapy
follicular lymphoma
conjugated bilirubin
b-cell lymphoma
pegfilgrastim
pet/ct scan
r-chop
high grade b-cell lymphoma
indolent lymphoma

Summary

This phase I/Ib trial studies the side effects and best dose of parsaclisib plus the standard drug therapy (rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone [R-CHOP]) and to see how well they work compared with R-CHOP alone in treating patients with newly diagnosed, high risk diffuse large B-cell lymphoma. Parsaclisib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Rituximab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. Drugs used in chemotherapy, such as cyclophosphamide, 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. Anti-inflammatory drugs, such as prednisone, lower the body's immune response and are used with other drugs in the treatment of some types of cancer. It is not yet known if giving parsaclisib and R-CHOP together works better than R-CHOP alone in treating patients with high risk diffuse large B-cell lymphoma.

Description

PRIMARY OBJECTIVES:

I. To establish the maximum tolerated dose (MTD) of parsaclisib in combination with R-CHOP in newly diagnosed diffuse large B-cell lymphoma (DLBCL). (Phase I) II. To assess the complete metabolic response rate by positron emission tomography (PET) (PET complete response [CR]) of combining parsaclisib and R-CHOP in patients with newly diagnosed DLBCL. (Dose Expansion)

SECONDARY OBJECTIVES:

I. To describe the toxicities associated with parsaclisib in combination with R-CHOP. (Phase I) II. To assess the objective response rate (ORR) of parsaclisib in combination with R-CHOP. (Dose Expansion) III. To assess the duration of response (DOR), event-free survival (EFS), progression-free survival (PFS), and overall survival (OS). (Dose Expansion) IV. To further describe the toxicities associated with parsaclisib in combination with R-CHOP. (Dose Expansion)

OUTLINE: This is a dose-escalation study of parsaclisib.

Patients receive parsaclisib orally (PO) once daily (QD) on days 1-10 or 1-14, rituximab intravenously (IV) or biosimilar substitute, cyclophosphamide IV over 30 minutes, doxorubicin hydrochloride IV, and vincristine sulfate IV over 15 minutes on day 1. Patients also receive prednisone PO on days 1-5 and pegfilgrastim subcutaneously (SC) or biosimilar substitute on day 2. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months during year 1 and every 4 months during year 2. Patients who experience disease progression before the end of year 2 are followed up every 6 months until 5 years after registration.

Details
Condition Ann Arbor Stage II Diffuse Large B-Cell Lymphoma, Ann Arbor Stage II Follicular Lymphoma, Ann Arbor Stage II Marginal Zone Lymphoma, Ann Arbor Stage III Diffuse Large B-Cell Lymphoma, Ann Arbor Stage III Follicular Lymphoma, Ann Arbor Stage III Marginal Zone Lymphoma, Ann Arbor Stage IV Diffuse Large B-Cell Lymphoma, Ann Arbor Stage IV Follicular Lymphoma, Ann Arbor Stage IV Marginal Zone Lymphoma, Diffuse Large B-Cell Lymphoma, High Grade B-Cell Lymphoma With MYC and BCL2 and/or BCL6 Rearrangements, High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 Rearrangements, High Grade B-Cell Lymphoma With MYC, BCL2, and BCL6 Rearrangements, Indolent Non-Hodgkin Lymphoma
Treatment Rituximab, cyclophosphamide, doxorubicin hydrochloride, prednisone, vincristine sulfate, pegfilgrastim, Parsaclisib
Clinical Study IdentifierNCT04323956
SponsorMayo Clinic
Last Modified on16 June 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

Newly diagnosed, untreated, histologically confirmed diffuse large B-cell lymphoma expressing the CD20 antigen, with ANY of the following
Age >= 18 years
Non-germinal center B-cell (GCB) subtype by Hans algorithm
Myc expression >= 40% by immunohistochemistry (IHC)
Bcl-2 expression >= 50% by IHC
Myc expression >= 40% AND Bcl-2 expression >= 50% by IHC (double expressor)
MYC rearrangement by fluorescence in situ hybridization (FISH)
Or high-grade B-cell lymphoma with MYC rearrangement AND BCL2 and/or BCL6 rearrangement (double-hit or triple-hit lymphoma) but not a candidate for more aggressive chemotherapy (such as cyclophosphamide, Oncovin [vincristine], doxorubicin, [CODOX]-methotrexate [M]- ifosfamide, Vepesid [etoposide], Ara-C [cytarabine] [IVAC])
NOTE: Patients with a new diagnosis of concurrent DLBCL and an indolent lymphoma (previously undiagnosed, such as follicular lymphoma or marginal zone lymphoma) are eligible. However, patients with a known prior diagnosis of indolent lymphoma with new transformation to DLBCL (i.e., transformed lymphoma) are not eligible
Measurable disease (at least 1 lesion of >= 1.5 cm in one diameter) as detected by computed tomography (CT) or the CT images of PET/CT. Skins lesions can be used if the area is >= 2 cm in at least one diameter and photographed with a ruler
Ann Arbor stages II (bulky disease, i.e., >= 5 cm, or not a candidate for combined
Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2
modality treatment with R-CHOP plus radiotherapy), III, or IV
Absolute neutrophil count (ANC) >= 1500/mm^3 (obtained =< 14 days prior to registration)
Platelet count >= 100,000/mm^3 (obtained =< 14 days prior to registration)
Total bilirubin =< 1.5 x upper limit of normal (ULN), or if total bilirubin is > 1.5 x ULN, the direct bilirubin must be normal (obtained =< 14 days prior to registration)
Aspartate transaminase (AST) =< 3 x ULN (=< 5 x ULN for patients with direct liver involvement by lymphoma) (obtained =< 14 days prior to registration)
Alkaline phosphatase =< 3 x ULN, unless evidence of the direct liver involvement by lymphoma, then =< 5 x ULN (obtained =< 14 days prior to registration)
Calculated creatinine clearance of >= 30 mL/min using the Cockcroft-Gault formula (obtained =< 14 days prior to registration)
Negative urine pregnancy test done =< 7 days prior to registration, for persons of childbearing potential only
NOTE: If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
Persons of childbearing potential must agree to use one reliable form of birth control
Provide written informed consent
Willingness to provide mandatory research blood specimens for banking
Willing to return to enrolling institution for follow-up (during the Active Monitoring Phase of the study)

Exclusion Criteria

Any of the following because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are
unknown
Pregnant persons
Nursing persons (lactating persons are eligible provided that they agree not to breast feed while taking parsaclisib)
Persons of childbearing potential who are unwilling to employ adequate contraception
Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
Primary central nervous system (CNS) lymphoma, or parenchymal, meningeal or
Immunocompromised patients and patients known to be human immunodeficiency virus (HIV) positive and currently receiving antiretroviral therapy (except for patients on effective antiretroviral therapy with undetectable viral load within 6 months)
cerebrospinal fluid involvement with malignant lymphoma cells
NOTE: If evidence of chronic hepatitis B virus (HBV) infection, HBV viral load must be undetectable on suppressive therapy if indicated
NOTE: If history of hepatitis C virus (HCV) infection, HCV viral load must be undetectable
Uncontrolled intercurrent illness including, but not limited to
Ongoing or active infection
Symptomatic congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
Unstable angina pectoris
Cardiac arrhythmia
Ongoing inflammatory bowel disease (such as ulcerative colitis) or other colitis requiring active treatment
Oxygen dependent baseline lung disease (such as interstitial lung disease or chronic obstructive pulmonary disease [COPD])
Or psychiatric illness/social situations that would limit compliance with study requirements
Other active malignancy requiring therapy such as radiation, chemotherapy or immunotherapy. Patients on hormonal therapy for treated breast or prostate cancer are permitted if they meet other eligibility criteria
EXCEPTIONS: Localized non-melanotic skin cancer or any cancer that in the judgment of the investigator has been treated with curative intent (e.g., disease-free survival equal or more than 5 years) and will not interfere with the study treatment plan and response assessment
NOTE: If there is a history of prior malignancy, they must not require therapy such as radiation, chemotherapy or immunotherapy for their cancer
Received or receiving any other agent which would be considered as a treatment for the
lymphoma (with the exception of corticosteroid)
>= 25% of bone marrow radiated for other diseases
Ejection fraction of < 45% by either multigated acquisition scan (MUGA) or echocardiogram (ECHO)
History of myocardial infarction =< 6 months, or congestive heart failure requiring
use of ongoing maintenance therapy for life-threatening ventricular
arrhythmias
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