| Eligibility |
Inclusion Criteria:
- Patients must have histologically proven diagnosis of lymphoid malignancy according to
World health organization (WHO) defined as:
a. Mature T cell lymphoma: (i) Peripheral T-Cell lymphoma not otherwise specified
(PTCL, NOS) (ii) Anaplastic large T cell lymphoma, ALK +ve (ALCL ALK+) (iii)
Anaplastic large T cell lymphoma, ALK +ve (ALCL ALK-) (iv) Angioimmunobastic T cell
lymphoma (AITL) (v) Enteropathy associated T-cell lymphoma ((EATL) (vi) Estranodal NK
T cell lymphoma (ENKTL) b. T-cell Prolymphocytic leukemia c. Aggressive NK-cell
leukemia d. Adult T-cell leukemia/lymphoma e. Hepatosplenic T-cell lymphoma f. Primary
cutaneous T cell lymphoma: (i) Mycosis fungoides (ii) Primary cutaneous CD30+ve T cell
lymphoproliferative disorder (iii) Primary cutaneous peripheral T cell lymphoma, NOS
(iv) Subcutaneous panniculitis-like T-cell lymphoma (v) Primary cutaneous gamma/delta
T cell lymphoma (vi) Primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell
lymphoma g. Mantle cell lymphoma h. Diffuse large B cell lymphoma, NOS i. Primary
mediastinal large B cell lymphoma j. High grade B cell lymphoma, NOS k. High grade B
cell lymphoma with myc and bcl2 and/or bcl6 rearrangements
- Disease specific eligibility:
1. Mature T cell lymphoma, T cell prolymphocytic leukemia, aggressive NK-cell
leukemia, adult T-cell leukemia/lymphoma, hepatosplenic T-cell lymphoma,
subcutaneous panniculitis-like T cell lymphoma, primary cutaneous gamma/delta T
cell lymphoma, primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell
lymphoma: Patient must have progressed after one line of therapy and ineligible
for hematopoietic stem cell transplantation ,or progressed on two lines of
therapy with no available curative options per investigator discretion.
2. Mantle cell lymphoma: Patients must have progressed after at least two line of
therapy with no available options that would provide clinical benefit per
investigator discretion. Patients with prior Chimeric Antigen Receptor T cell
(CART cells) therapy are allowed .
3. Diffuse large B cell lymphoma NOS, primary mediastinal large B cell lymphoma,
high grade B cell lymphoma NOS, high grade B cell lymphoma with myc, bcl2 and/or
bcl6 rearrangements: Patients must have progressed on at least two lines of
therapy with no available options that would provide clinical benefit per
investigator discretion. Patients with prior Chimeric Antigen Receptor T cell
(CART cells) therapy are allowed.
- Patients must have measurable disease with a lymph node or tumor mass > 1.5 cm in at
least one dimension as assessed by computed tomography (CT)
- Patients must be = 18 years of age.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 (corresponds to
Karnofsky Performance Status [KPS] = 80%).
- Patients must have adequate organ and marrow function as defined in protocol.
- Willingness to avoid pregnancy or fathering children based on the following criteria:
a. Woman of non-childbearing potential (ie, surgically sterile with a hysterectomy
and/or bilateral oophorectomy OR = 12 months of amenorrhea and at least 45 years of
age). b. Woman of childbearing potential who has a negative serum pregnancy test at
screening and who agrees to take appropriate precautions to avoid pregnancy (with at
least 99% certainty) from screening through safety follow-up. Permitted methods that
are at least 99% effective in preventing pregnancy (see Appendix A) should be
communicated to the subject and their understanding confirmed.
c. Man who agrees to take appropriate precautions to avoid fathering children (with at
least 99% certainty) from screening through at least 93 days after the last dose of
study treatment. Permitted methods that are at least 99% effective in preventing
pregnancy
Exclusion Criteria:
- History of central nervous system lymphoma (either primary or metastatic).
- Allogeneic stem cell transplant within the last 6 months, or autologous stem cell
transplant within the last 3 months before the date of the first dose of study
treatment.
- Active graft-versus-host disease
- Ongoing treatment with chronic immunosuppressants (e.g., cyclosporine) or systemic
steroids >20 mg of prednisone (or equivalent) once daily (QD)
- Receipt of anticancer medications or investigational drugs within the following
intervals before the first dose of study treatment:a. < 6 weeks for mitomycin-C or
nitrosoureas.b. < 4 weeks for immunotherapy.c. < 3 weeks for radiotherapy. d. < 2
weeks for any investigational agent or other anticancer medications or equal to 5 half
lives of the investigational drug, whichever is longer.
- Prior CART cells therapy within 90 days of enrollment or if they have not recovered
from CART cells therapy toxicity to grade 1 or less.
- Inadequate recovery from toxicity and/or complications from a major surgery before the
date of the first dose of study treatment.
- Prior treatment-related toxicities have not resolved to NCI CTCAE v5 = Grade 1 before
the date of the first dose of study treatment except for stable chronic toxicities
(Grade = 2) not expected to resolve (eg, stable Grade 2 peripheral neurotoxicity).
- Concurrent anticancer therapy (eg, chemotherapy, radiation therapy, surgery,
immunotherapy, biologic therapy, hormonal therapy, investigational therapy, or tumor
embolization).
- Use or expected use during the study of any prohibited medications, including potent
CYP3A4 inhibitors or inducers within 14 days or 5 half-lives (whichever is longer)
before the date of study treatment administration (see appendix 11.1) in addition to
excluding patients on CYP3A inducers.
- Significant concurrent, uncontrolled medical condition, including, but not limited to,
renal, hepatic, hematological, GI, endocrine, pulmonary, neurological, cerebral, or
psychiatric disease.
- Current or previous other malignancy within 3 years of study entry, except cured basal
or squamous cell skin cancer, superficial bladder cancer, prostate intraepithelial
neoplasm, carcinoma in situ of the cervix, or other noninvasive or indolent malignancy
without PI approval.
- History of stroke or intracranial hemorrhage within 6 months of the date of study
treatment administration.
- Chronic or current active infectious disease requiring systemic antibiotics,
antifungal, or antiviral treatment or exposure to a live vaccine within 30 days of
study treatment.
- Known HIV infection or positivity on immunoassay.
- Active cytomegalovirus (CMV) or Epstein-Barr virus (EBV) infection (i.e., subjects
with detectable viral load). Positive CMV or EBV result is acceptable with
confirmation of no active infection.
- Hepatitis B (HBV) or hepatitis C (HCV) infection: Subjects with a positive hepatitis B
surface antigen [HBsAg] or hepatitis C antibody [HCV Ab] will be excluded. Subjects
with a positive hepatitis B core antibody (HBcAb) must have negative hepatitis B virus
(HBV) deoxyribonucleic acid (DNA) to be eligible, must receive prophylaxis with
entecavir (or equivalent) concomitant with duvelisib treatment, and must be
periodically monitored for HBV reactivation by institutional guidelines. Investigators
who strongly believe that a positive HBcAb is false due to passive immunization from
previous immunoglobulin infusion therapy should consider the risk-benefit for the
patient given the potential for reactivation
- History of tuberculosis treatment within the 2 years prior to randomization
- Clinically significant cardiac disease, including unstable angina, acute myocardial
infarction, and/or cardiac conduction issues within 6 months of the date of study
treatment administration.
- Current New York Heart Association Class II to IV congestive heart failure or
uncontrolled arrhythmia.
- Presence of an abnormal ECG that is clinically meaningful. Screening QTc interval 450
milliseconds is excluded (corrected by Fridericia). In the event that a single QTc is
> 450 milliseconds, the subject may enroll if the average QTc for 3 ECGs is < 450
milliseconds.
- Unable to swallow and retain oral medication, malabsorption syndrome, disease
significantly affecting GI function, total resection of the stomach or small bowel,
ulcerative colitis, symptomatic inflammatory bowel disease, or partial or complete
bowel obstruction.
- Unable to receive prophylactic treatment for pneumocystis, herpes simplex virus (HSV),
or herpes zoster (VZV) at screening
- Known hypersensitivity or severe reaction to duvelisib or BMS-986345 or its excipients
(refer to the IB).
- History of serious allergic reactions including anaphylaxis and toxic epidermal
necrolysis.
- Currently pregnant or breastfeeding
- Any condition that would, in the investigator's judgment, interfere with full
participation in the study, including administration of study treatment and attending
required study visits; pose a significant risk to the subject; or interfere with
interpretation of study data.
- Inability to comprehend or unwilling to sign the informed consent form
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