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Ann Arbor Stage II Diffuse Large B-Cell LymphomaPhase 1NCT04323956

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

A Phase 1 study testing Cyclophosphamide, Doxorubicin Hydrochloride and Parsaclisib in people with Ann Arbor Stage II Diffuse Large B-Cell Lymphoma and Ann Arbor Stage II Follicular Lymphoma, run by Mayo Clinic at 3 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record

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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Cyclophosphamide, Doxorubicin Hydrochloride and Parsaclisib
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
50 participants
Where
3 sitesUnited States
Study dates
15 Jun 2020to 16 May 2028
Phase
Phase 1

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)
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  • 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)
  • 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)

Who cannot join

  • 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
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  • 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
  • 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
  • Received or receiving any other agent which would be considered as a treatment for the lymphoma (with the exception of corticosteroid)
  • 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
  • History of myocardial infarction =< 6 months, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
  • >= 25% of bone marrow radiated for other diseases
  • Ejection fraction of < 45% by either multigated acquisition scan (MUGA) or echocardiogram (ECHO)

Trial locations and contacts

3 sites in 1 country.

United States3 sites

  • Mayo Clinic in Florida

    Jacksonville, Florida, 32224-9980

  • Mayo Clinic in Rochester

    Rochester, Minnesota, 55905

  • Mayo Clinic in Arizona

    Scottsdale, Arizona, 85259

Other trials in United States

About this study

Official title: Phase I/Ib Study of Parsaclisib (INCB50465), Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (PaR-CHOP) Immunochemotherapy for Patients With Newly Diagnosed High Risk Diffuse Large B-Cell Lymphoma

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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) III. To assess significant toxicities of parsaclisib in combination with polatuzumab vedotin (pola) and R-CHP in newly diagnosed DLBCL. (Pola Safety Lead-in)

SECONDARY OBJECTIVES:

  1. 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) in patients treated with parsaclisib in combination with R-CHOP. (Dose Expansion) IV. To further describe the toxicities associated with parsaclisib in combination with R-CHOP. (Dose Expansion) V. To describe the toxicities associated with parsaclisib in combination with polatuzumab vedotin and R-CHP. (Pola Safety Lead-in) VI. To assess the PET CR rate and ORR of parsaclisib in combination with polatuzumab vedotin and R-CHP. (Pola Safety Lead-in) VII. To assess the duration of response (DOR), event-free survival (EFS), progression-free survival (PFS), and overall survival (OS) in patients treated with parsaclisib in combination with polatuzumab vedotin and R-CHP. (Pola Safety Lead-in)

OUTLINE: This is a phase I, dose-escalation study of parsaclisib, and safety lead-in of pola.

ARM I (PHASE I AND DOSE EXPANSION): 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.

ARM II (PHASE I AND POLA SAFETY LEAD-IN): 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.

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.

Being tested
Cyclophosphamide, Doxorubicin Hydrochloride, Parsaclisib, Pegfilgrastim, Polatuzumab Vedotin
Medical subject headings
Lymphoma, Large B-Cell, Diffuse

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CyclophosphamideDrug

    Also called (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida

    Given IV

  • Doxorubicin HydrochlorideDrug

    Also called 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

    Given IV

  • ParsaclisibDrug

    Also called (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

    Given PO

  • PegfilgrastimBiological

    Also called Filgrastim SD-01, filgrastim-SD/01, Fulphila, HSP-130

    Given SC

  • Polatuzumab VedotinDrug

    Also called ADC DCDS4501A, Antibody-Drug Conjugate DCDS4501A, DCDS4501A, FCU 2711

    Given IV

  • PrednisoneDrug

    Also called .delta.1-Cortisone, 1, 2-Dehydrocortisone, Adasone, Cortancyl

    Given PO

  • RituximabBiological

    Also called ABP 798, BI 695500, C2B8 Monoclonal Antibody, Chimeric Anti-CD20 Antibody

    Given IV

  • Vincristine SulfateDrug

    Also called Kyocristine, Leurocristine Sulfate, Leurocristine, sulfate, Oncovin

    Given IV

Study groups in NCT04323956
Study groupRoleWhat they receive
Arm I (parsaclisib, R-CHOP)ExperimentalPatients 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.
Receives: Drug: Cyclophosphamide; Drug: Doxorubicin Hydrochloride; Drug: Parsaclisib; Biological: Pegfilgrastim; Drug: Prednisone; Biological: Rituximab; Drug: Vincristine Sulfate
Arm II (parsaclisib, R-CHOP, polatuzumab vedotin)Active comparatorPatients 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.
Receives: Drug: Cyclophosphamide; Drug: Doxorubicin Hydrochloride; Drug: Parsaclisib; Biological: Pegfilgrastim; Drug: Polatuzumab Vedotin; Drug: Prednisone; Biological: Rituximab; Drug: Vincristine Sulfate

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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).

    Measured: Up to 21 days

  2. 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.

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

Secondary outcomes (12)

  1. Incidence of adverse events (AEs) (Phase I)

    The number and severity (grade) of all treatment related AEs will be tabulated and summarized. Non-hematologic AEs will be evaluated via the ordinal Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0 standard AE 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 CTCAE v 5.0 standard AE grading. Both all grade and grade 3 and above AEs will be described and summarized in a similar fashion. Overall AE incidences as well as AE profiles by dose level and patient will be explored and summarized. Frequency distributions, graphical techniques and other descriptive measures will form the basis of these analyses.

    Measured: Up to 2 years

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

    Toxicity will be measured per NCI-CTCAE version 5. Significant toxicity is defined as an adverse event occurring during the first cycle of treatment that is possibly, probably, or definitely related to study treatment.

    Measured: Up to cycle 1 (21 days)

  3. Objective response rate (Dose Expansion)

    Will be estimated by the number of patients with an objective status of CMR or partial metabolic response (PMR) by the PET-CT based response criteria at the end of treatment divided by the total number of evaluable patients. All evaluable patients will be used for this analysis. Exact binomial 95% confidence intervals for the true objective response rate will be calculated.

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

  4. Duration of response (Dose Expansion)

    Defined as the date at which the patient's objective status is first noted to be either CMR or PMR to the earliest date progression is documented by CT or PET/CT [progressive metabolic disease (PMD) or progressive disease (PD)]

    Measured: Up to 2 years

  5. Event-free survival (Dose Expansion)

    Defined as the time from registration to disease progression or relapse (PMD or PD), initiation of subsequent anti-lymphoma therapy, or death due to any cause.

    Measured: Up to 5 years

  6. Progression-free survival (Dose Expansion)

    Defined as the time from registration to progression (PMD or PD) or death due to any cause

    Measured: Up to 5 years

  7. Overall survival (Pola Safety Lead-in)

    Defined as the time from registration until death due to any cause.

    Measured: Up to 5 years

  8. Incidence of adverse events (Dose Expansion)

    The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine patterns. Additionally, the relationship of the adverse event(s) to the study treatment will be taken into consideration.

    Measured: Up to 2 years

  9. Objective response rate (Pola Safety Lead-in)

    Will be estimated by the number of patients with an objective status of CMR or PMR by the PET-CT based response criteria at the end of treatment divided by the total number of evaluable patients. All evaluable patients will be used for this analysis. Exact binomial 95% confidence intervals for the true objective response rate will be calculated.

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

  10. Duration of response (Pola Safety Lead-in)

    Defined as the date at which the patient's objective status is first noted to be either CMR or PMR to the earliest date progression is documented by CT or PET/CT (PMD or PD)

    Measured: Up to 2 years

  11. Event-free survival (Pola Safety Lead-in)

    Defined as the time from registration to disease progression or relapse (PMD or PD), initiation of subsequent anti-lymphoma therapy, or death due to any cause

    Measured: Up to 5 years

  12. Progression-free survival (Pola Safety Lead-in)

    Defined as the time from registration to progression (PMD or PD) or death due to any cause

    Measured: Up to 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Mar 2020
  2. Study start15 Jun 2020
  3. Primary completion4 Oct 2023
  4. Study completion16 May 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
50 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04323956
Sponsor's protocol ID
MC1986
Other IDs
NCI-2020-01855, 19-005387
Status last verified
Jan 2026
First submitted
25 Mar 2020
Last updated
2 Feb 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

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