Trial Title:
Pembrolizumab + Chemotherapy in Newly Diagnosed PCNSL
NCT ID:
NCT06475235
Condition:
Lymphoma
Primary Central Nervous System Lymphoma
Conditions: Official terms:
Lymphoma
Rituximab
Pembrolizumab
Methotrexate
Temozolomide
Conditions: Keywords:
Lymphoma
Primary Central Nervous System Lymphoma
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Sequential Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Pembrolizumab
Description:
Humanized immunoglobin G4 monoclonal antibody, 4 mL vials, via intravenous infusion (into
the vein) per protocol.
Arm group label:
Consolidation Treatment:
Arm group label:
Induction Treatment:
Other name:
Keytruda
Other name:
MK-3475
Other name:
Humanized X PD-1 mAb (H409A11) IgG4
Intervention type:
Drug
Intervention name:
Methotrexate
Description:
Anti-metabolite, 50 mL vials, via intravenous infusion per protocol.
Arm group label:
Induction Treatment:
Other name:
MTX
Intervention type:
Drug
Intervention name:
Temozolomide
Description:
Alkylating agent, 5, 20, 100, 140, 180, or 250 mg capsules, taken orally per protocol.
Arm group label:
Induction Treatment:
Other name:
Temodar
Other name:
Temodal
Intervention type:
Drug
Intervention name:
Rituximab
Description:
Anti-CD20 antibody, 10 or 50 mL single-use vials, via intravenous infusion per standard
of care.
Arm group label:
Induction Treatment:
Other name:
Riabni
Other name:
Rituxan
Other name:
Ruxience
Other name:
Truxima
Summary:
This research study is studying if the investigational drug, Pembrolizumab, in
combination with chemotherapy helps primary central nervous system lymphoma with
acceptable side effects.
This research study involves a combination of the below drugs:
- Pembrolizumab (a type of monoclonal antibody)
- Methotrexate (a type of anti-metabolite)
- Temozolomide (a type of alkylating agent)
- Rituximab (a type of antibody)
Detailed description:
This is an open label, pilot trial of Pembrolizumab in combination with chemotherapy in
participants with newly diagnosed Primary Central Nervous System Lymphoma (PCNSL).
The U.S. Food and Drug Administration (FDA) has not approved Pembrolizumab for Primary
Central Nervous System Lymphoma (PCNSL) but it has been approved for other uses.
The FDA has approved Rituximab for PCNSL.
The FDA has not approved Temozolomide for PCNSL but it has been approved for other uses.
The FDA has not approved Methotrexate for PCNSL but it has been approved for other uses.
The research study procedures include screening for eligibility, blood and urine tests,
Computerized Tomography (CT) scans, Magnetic Resonance Imaging (MRI) scans, Positron
Emission Tomography (PET) scans, testicular ultrasounds, electrocardiograms (ECG), and
eye exams.
It is expected that about 15 people will take part in this research study.
Merck & Co. is supporting this research study by providing the study drug pembrolizumab.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Subjects with pathologically confirmed newly diagnosed primary CNS diffuse large
B-cell lymphoma (DLBCL) confirmed by one of the following:
- Brain biopsy or resection
- Cerebrospinal fluid
- Vitreous fluid
- Participants must not have any evidence or history of DLBCL outside of the CNS
- Participants must not have received any chemotherapy or radiation therapy directed
to PCNSL.
- Age ≥18 years.
- Ability to understand and the willingness to sign a written informed consent form
document.
- ECOG performance status ≤2 (Karnofsky ≥70% will be considered if related to PCNSL,
see Appendix A).
- Participants must have adequate organ function as defined below.
- Hematology
- Absolute neutrophil count (ANC) ≥1000/µL
- Platelets ≥100 000/µL
- Hemoglobin ≥9.0 g/dL or ≥5.6 mmol/L (Criteria must be met without
erythropoietin dependency and without packed red blood cell (pRBC) transfusion
within last 2 weeks)
- Renal
-- Creatinine ≤1.5 x ULN OR Measured or calculated creatinine clearance ≥40 mL/min
for participant with creatinine levels >1.5 × institutional ULN (Creatinine
clearance (CrCl) should be calculated per institutional standard.)
- Hepatic
- Total bilirubin ≤1.5 x ULN OR direct bilirubin ≤ULN for participants with total
bilirubin levels >1.5 x ULN
- AST (SGOT) and ALT (SGPT) ≤2.5 × ULN (≤5 × ULN for participants with liver
metastases)
- Coagulation
--International normalized ratio (INR) OR prothrombin time (PT) and activated
partial thromboplastin time (aPTT) ≤1.5 × ULN unless participant is receiving
anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended
use of anticoagulants
- Participants must have negative HIV serology.
- Participants must have no history of organ transplantation or ongoing
immunosuppressant therapy.
- Women of child-bearing potential (WOCBP), defined as all women physiologically
capable of becoming pregnant, must have a negative serum pregnancy within 72 hours
prior to registration.
- Women in the following categories are not considered WOCBP:
- Premenarchal
- Premenopausal female with 1 of the following:
- Documented hysterectomy
- Documented bilateral salpingectomy
- Documented bilateral oophorectomy
- Note: Documentation can come from the site personnel's review of the
participant's medical records, medical examination, or medical history
interview.
- Post-menopausal female is defined as no menses for 12 months without an alternative
medical cause.
- A high follicle stimulating hormone (FSH) level in the postmenopausal range may
be used to confirm a postmenopausal state in women not using hormonal
contraception or hormonal replacement therapy (HRT). However, in the absence of
12 months of amenorrhea, confirmation with two FSH measurements in the
postmenopausal range is required.
- Females on HRT and whose menopausal status is in doubt will be required to use
one of the non-hormonal highly effective contraception methods if they wish to
continue their HRT during the study. Otherwise, they must discontinue HRT to
allow confirmation of postmenopausal status before study enrollment.
- Women of child-bearing potential (WOCBP; see definition above), must agree to use a
highly effective method of contraception consistently and correctly as described
below during study treatment and for 120 days after study discontinuation.
-
1. Highly Effective Contraceptive Methods That Are User Dependent (Failure
rate of < 1% per year when used consistently and correctly.)
- a. Combined (estrogen- and progestogen- containing) hormonal contraception
- i. Oral
- ii. Intravaginal
- iii. Transdermal
- iv. Injectable
- b. Progestogen-only hormonal contraception b, c
- i. Oral
- ii. Injectable
-
2. Highly Effective Methods That Have Low User Dependency (Failure rate of
<1% per year when used consistently and correctly)
- a. Progestogen- only contraceptive implant b, c
- b. Intrauterine hormone-releasing system (IUS) b
- c. Intrauterine device (IUD)
- d. Bilateral tubal occlusion
- e. Vasectomized partner: A vasectomized partner is a highly effective
contraception method provided that the partner is the sole male sexual
partner of the WOCBP and the absence of sperm has been confirmed. If not,
an additional highly effective method of contraception should be used.
- f. Sexual abstinence: Sexual abstinence is considered a highly effective
method only if defined as refraining from heterosexual intercourse during
the entire period of risk associated with the study treatment. The
reliability of sexual abstinence needs to be evaluated in relation to the
duration of the study and the preferred and usual lifestyle of the
participant.
- NOTES: Use should be consistent with local regulations regarding the use of
contraceptive methods for participants of clinical studies.
- a. Typical use failure rates are lower than perfect-use failure rates (i.e.
when used consistently and correctly).
- b. If hormonal contraception efficacy is potentially decreased due to
interaction with study treatment, condoms must be used in addition to the
hormonal contraception during the treatment period and for at least during
study treatment and for 120 days after study discontinuation after the last
dose of study treatment.
- c. If locally required, in accordance with Clinical Trial Facilitation Group
(CTFG) guidelines, acceptable contraceptive implants are limited to those which
inhibit ovulation.
- Male participants must to use at least one of the following methods of contraception
starting with the first dose of study therapy through 120 days after the last dose
of therapy:
- Be abstinent from penile-vaginal intercourse as their usual and preferred
lifestyle (abstinent on a long term and persistent basis) and agree to remain
abstinent
- Use a male condom plus partner use of a contraceptive method with a failure
rate of <1% per year as described in Eligibility criterion 3.1.11 when having
penile-vaginal intercourse with a woman of childbearing potential who is not
currently pregnant.
- Note: Men with a pregnant or breastfeeding partner must agree to remain abstinent
from penile- vaginal intercourse or use a male condom during each episode of penile
penetration.
Exclusion Criteria:
- Participants who cannot undergo MRI
- Intraocular PCNSL without evidence of brain or spinal cord disease.
- Participants who are receiving any other investigational agents.
- History of allergic reactions or severe hypersensitivity reactions (≥grade 3)
attributed to compounds of similar chemical or biologic composition to
pembrolizumab, high-dose methotrexate, temozolomide, rituximab and/or any of its
excipients.
- Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or
with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg,
CTLA-4, OX-40, CD137)
- Has active autoimmune disease that has required systemic treatment in the past 2
years (i.e. with use of disease modifying agents, corticosteroids or
immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or
physiologic corticosteroid replacement therapy for adrenal or pituitary
insufficiency, etc.) is not considered a form of systemic treatment
- Has received a live vaccine within 30 days prior to the first dose of study drug.
Examples of live vaccines include, but are not limited to, the following: measles,
mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus
Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for
injection are generally killed virus vaccines and are allowed; however, intranasal
influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.
COVID19 vaccines are allowed.
- Has a known additional malignancy that is progressing or has required active
treatment within the past 3 years. Note: Participants with basal cell carcinoma of
the skin, squamous cell carcinoma of the skin, transitional cell carcinoma of
urothelial cancer, or carcinoma in situ (e.g. breast carcinoma, cervical cancer in
situ) that have undergone potentially curative therapy are not excluded.
- Has a history of (non-infectious) pneumonitis that required steroids or has current
pneumonitis.
- Patient has poorly controlled diabetes mellitus with a glycosylated hemoglobin >8%
or poorly controlled steroid-induced diabetes mellitus with a glycosylated
hemoglobin of >8%.
- Unable to swallow capsules or disease significantly affecting gastrointestinal
function, such as malabsorption syndrome, resection of the stomach or small bowel,
or complete bowel obstruction.
- Concurrent administration of medications or foods that are moderate or strong
inhibitors or strong inducers of cytochrome P450 (CYP) 3A4/5 (need to be
discontinued 2 weeks before starting study treatment)
- Enzyme-inducing antiepileptic drugs (EIAED) need to be discontinued and switched to
a non-EIAED 2 weeks prior to starting on trial drugs
- Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg]
reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is
detected) infection.
- Has a known history of active TB (Bacillus Tuberculosis)
- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
(in dosing exceeding 10 mg daily of prednisone equivalent)
- Patients who have undergone prior allogeneic stem cell transplant
- Patients who have large pleural effusions, ascites or full body edema
- Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial
- Is pregnant or breastfeeding or expecting to conceive or father children within the
projected duration of the study, starting with the screening visit through 120 days
after the last dose of trial treatment
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Brigham and Women's Hospital
Address:
City:
Boston
Zip:
02115
Country:
United States
Status:
Recruiting
Contact:
Last name:
Lakshmi Nayak, MD
Phone:
617-632-2166
Email:
Lakshmi_Nayak@DFCI.HARVARD.EDU
Contact backup:
Last name:
Lakshmi Nayak, MD
Facility:
Name:
Dana Farber Cancer Institute
Address:
City:
Boston
Zip:
02215
Country:
United States
Status:
Recruiting
Contact:
Last name:
Lakshmi Nayak, MD
Phone:
(617) 632-2166
Email:
Lakshmi_Nayak@DFCI.HARVARD.EDU
Contact backup:
Last name:
Lakshmi Nayak, MD
Start date:
October 2024
Completion date:
June 30, 2027
Lead sponsor:
Agency:
Dana-Farber Cancer Institute
Agency class:
Other
Collaborator:
Agency:
Merck Sharp & Dohme LLC
Agency class:
Industry
Source:
Dana-Farber Cancer Institute
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06475235
