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

NCT04323956 | Active Not Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: MC1986NCI-2020-0185519-005387
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 3

Brief Summary

This phase I/Ib trial studies the side effects and best dose of parsaclisib with or without polatuzumab-vedotin (Pola) plus the standard drug therapy (rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone \[PaR-CHOP\]) 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. Polatuzumab-vedotin is a monoclonal antibody, called polatuzumab, linked to a chemotherapy drug, called vedotin. Polatuzumab is a form of targeted therapy because it attaches to specific molecules (receptors) on the surface of cancer cells, known as anti-CD79b receptors, and delivers vedotin to kill them. 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.

Conditions

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; 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

Outcome Measures

Primary Outcomes (2)

• Maximum tolerated dose (MTD) of parsaclisib in combination with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) (Phase I)

  The MTD will be defined as the dose level below the lowest dose that induces dose-limiting toxicity in in at least one-third of patients (at least 2 of a maximum of 6 patients).

  Up to 21 days

• Complete metabolic response (CMR) rate (Dose Expansion)

  Will be measured by positron emission tomography (PET). A success is defined as an objective status of CMR by the PET-computed tomography (CT) based response criteria at the end of treatment. The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for the true rate of complete metabolic response will be calculated.

  Up to end of treatment (3-4 weeks after day 1 of cycle 6 [each cycle is 21 days])

Secondary Outcomes (12)

• Incidence of adverse events (AEs) (Phase I)

  Up to 2 years

• Incidence of toxicity due to parsaclisib in combination with Pola-R-CHP (Pola Safety Lead-in)

  Up to cycle 1 (21 days)

• Objective response rate (Dose Expansion)

  Up to end of treatment (3-4 weeks after day 1 of cycle 6 [each cycle is 21 days])

• Duration of response (Dose Expansion)

  Up to 2 years

• Event-free survival (Dose Expansion)

  Up to 5 years

Study Arms (2)

Arm I (parsaclisib, R-CHOP)

EXPERIMENTAL

Patients receive parsaclisib PO QD on days 1-10 or 1-14, rituximab 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 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.

Drug: Cyclophosphamide; Drug: Doxorubicin Hydrochloride; Drug: Parsaclisib; Biological: Pegfilgrastim; Drug: Prednisone; Biological: Rituximab; Drug: Vincristine Sulfate

Arm II (parsaclisib, R-CHOP, polatuzumab vedotin)

ACTIVE COMPARATOR

Patients receive parsaclisib PO once daily QD on days 1-10 or 1-14, polatuzumab vedotin IV over 90 minutes, rituximab 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 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.

Drug: Cyclophosphamide; Drug: Doxorubicin Hydrochloride; Drug: Parsaclisib; Biological: Pegfilgrastim; Drug: Polatuzumab Vedotin; Drug: Prednisone; Biological: Rituximab; Drug: Vincristine Sulfate

Interventions

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, Perrigo Prednisone, PRED, Predicor, Predicorten, Prednicen-M, Prednicort, Prednidib, Prednilonga, Predniment, Prednisone Intensol, Prednisonum, Prednitone, Promifen, Rayos, Servisone, SK-Prednisone

Arm I (parsaclisib, R-CHOP); Arm II (parsaclisib, R-CHOP, polatuzumab vedotin)

Rituximab BIOLOGICAL

Given IV

Also known as: 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, Riabni, Rituxan, Rituximab ABBS, Rituximab ARRX, Rituximab Biosimilar ABP 798, Rituximab Biosimilar BI 695500, Rituximab Biosimilar CT-P10, Rituximab Biosimilar GB241, Rituximab Biosimilar IBI301, Rituximab Biosimilar JHL1101, Rituximab Biosimilar PF-05280586, Rituximab Biosimilar RTXM83, Rituximab Biosimilar SAIT101, Rituximab Biosimilar SIBP-02, rituximab biosimilar TQB2303, Rituximab PVVR, rituximab-abbs, Rituximab-arrx, Rituximab-pvvr, RTXM83, Ruxience, Truxima, Ikgdar, Mabtas

Arm I (parsaclisib, R-CHOP); Arm II (parsaclisib, R-CHOP, polatuzumab vedotin)

Vincristine Sulfate DRUG

Given IV

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

Arm I (parsaclisib, R-CHOP); Arm II (parsaclisib, R-CHOP, polatuzumab vedotin)

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, Cyclophosphamide Monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR- 138719, Asta B 518, B-518, WR-138719

Arm I (parsaclisib, R-CHOP); Arm II (parsaclisib, R-CHOP, polatuzumab vedotin)

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, Doxorubicin.HCl, Doxorubin, Farmiblastina, FI 106, FI-106, hydroxydaunorubicin, Rubex

Arm I (parsaclisib, R-CHOP); Arm II (parsaclisib, R-CHOP, polatuzumab vedotin)

Parsaclisib DRUG

Given PO

Also known as: (4R)-4-(3-((1S)-1-(4-Amino-3-methyl-1H-pyrazolo(3,4-d)pyrimidin-1-yl)ethyl)-5-chloro-2-ethoxy-6-fluorophenyl)pyrrolidin-2-one, IBI376, INCB 50465, INCB-50465, INCB050465, INCB50465, WHO 10589

Arm I (parsaclisib, R-CHOP); Arm II (parsaclisib, R-CHOP, polatuzumab vedotin)

Pegfilgrastim BIOLOGICAL

Given SC

Also known as: Filgrastim SD-01, filgrastim-SD/01, Fulphila, HSP-130, Jinyouli, Neulasta, Neulastim, Nyvepria, PEG-filgrastim, Pegcyte, Pegfilgrastim Biosimilar HSP-130, Pegfilgrastim Biosimilar Nyvepria, Pegfilgrastim Biosimilar Pegcyte, Pegfilgrastim Biosimilar PF-06881894, Pegfilgrastim Biosimilar Udenyca, Pegfilgrastim Biosimilar Ziextenzo, pegfilgrastim-apgf, pegfilgrastim-bmez, pegfilgrastim-cbqv, Pegfilgrastim-jmdb, PF-06881894, SD-01, SD-01 sustained duration G-CSF, Udenyca, Ziextenzo, Neupopeg, Pegylated G-CSF, Pegylated GCSF, Pegylated Granulocyte Colony Stimulating Factor

Arm I (parsaclisib, R-CHOP); Arm II (parsaclisib, R-CHOP, polatuzumab vedotin)

Polatuzumab Vedotin DRUG

Given IV

Also known as: ADC DCDS4501A, Antibody-Drug Conjugate DCDS4501A, DCDS4501A, FCU 2711, polatuzumab vedotin-piiq, Polivy, RG7596, Ro 5541077-000

Arm II (parsaclisib, R-CHOP, polatuzumab vedotin)

Eligibility Criteria

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

You may qualify if:

• Age \>= 18 years
• Newly diagnosed, untreated, histologically confirmed diffuse large B-cell lymphoma expressing the CD20 antigen, with ANY of the following:
• 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
• Ann Arbor stages II (bulky disease, i.e., \>= 5 cm, or not a candidate for combined modality treatment with R-CHOP plus radiotherapy), III, or IV
• 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
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2
• 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)

You may not qualify if:

• 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
• Primary central nervous system (CNS) lymphoma, or parenchymal, meningeal or cerebrospinal fluid involvement with malignant lymphoma cells
• 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
• 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)
• 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

Sponsors & Collaborators

• Mayo Clinic: lead

Study Sites (3)

Mayo Clinic in Arizona

Scottsdale, Arizona, 85259, United States

Location

Mayo Clinic in Florida

Jacksonville, Florida, 32224-9980, United States

Location

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

Related Links

• Mayo Clinic Clinical Trials

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Interventions

Cyclophosphamide; Doxorubicin; parsaclisib; pegfilgrastim; pegylated granulocyte colony-stimulating factor; polatuzumab vedotin; Prednisone; deltacortene; prednylidene; Rituximab; CT-P10; Vincristine

Condition Hierarchy (Ancestors)

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

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; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines

Study Officials

• Yucai Wang, M.D., Ph.D.

  Mayo Clinic in Rochester

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 25, 2020
• First Posted: March 27, 2020
• Study Start: June 15, 2020
• Primary Completion: October 4, 2023
• Study Completion (Estimated): May 16, 2028
• Last Updated: February 2, 2026

Record last verified: 2026-01

Locations

US (3)