STARGLO (Closed) – Blood Cancer Research WA

STARGLO – NO LONGER RECRUITING

Starglo is a phase III, open-label, multicenter, randomized study evaluating the efficacy and safety of glofitamab in combination with gemcitabine plus oxaliplatin versus rituximab in combination with gemcitabine and oxaliplatin in patients with relapsed/refractory diffuse large b-cell lymphoma.

Relapsed/Refractory Diffuse Large B-cell Lymphoma

STARGLO is a trial comparing a standard chemotherapy program (R-GemOx) with chemotherapy (GemOx) and a new type of immunotherapy called glofitamab. Glofitamab has been tested in this subtype of lymphoma and shown to be an effective treatment. Patients who participate will have a 66% chance of treatment with the immunotherapy containing arm (GemOx and glofitamab) and a 33% chance of receiving the standard chemotherapy. This trial is suitable for patients with diffuse large B-cell lymphoma in whom the lymphoma has returned after at least one prior treatment.

Key Eligibility Criteria

▸ Histologically confirmed diffuse large B-cell lymphoma, NOS

Excluded:

History of transformation of indolent disease to DLBCL
High-grade B-cell lymphoma (HGBCL) with MYC and BCL2  and/or BCL6 rearrangements, and high-grade B-cell lymphoma NOS, as defined by to 2016 WHO guidelines;
- Patients classified as “double-hit” lymphoma with known MYC and BCL2 and/or BCL6 rearrangements are excluded.
- Patients with DLBCL characterized as “double expressors” without the above rearrangements will not be excluded.
Primary mediastinal B-cell lymphoma (PMBCL)
Primary or secondary central nervous system (CNS) lymphoma at the time of recruitment or history of CNS lymphoma

▸ R/R Disease:

Relapsed: disease that has recurred following a response that lasted ≥ 6 months after completion of the last line of therapy.
Refractory: disease that did not respond to or that progressed < 6 months after completion of the last line of therapy.

▸ At least one (≥1) line of prior systemic therapy

▸ 2L patients must be transplant ineligible as per criteria below:

Patients who have failed only one prior line of therapy must not be a candidate for high-dose chemotherapy followed by ASCT by meeting at least one of the following criteria:
- Left ventricular ejection fraction ≤40%
- CrCl or glomerular filtration rate ≤45 mL/min
- ECOG Performance Status of ≥2
- Age ≥70 years
- Patient refused high-dose chemotherapy and/or transplant
- Patient had insufficient response to pre-transplant chemotherapy to be able to proceed to transplant
- Other comorbidities or criteria that preclude use of transplant based on local practice standards or in the investigator’s opinion.

The rationale for transplant ineligibility must be documented in medical notes

▸ Availability of tumor tissue, unless unobtainable per investigator assessment. Freshly collected biopsy is preferred. Archival tissue is acceptable (most recent archival tumor tissue is preferred)

▸ Measurable disease (At least one bi-dimensionally measurable (≥1.5 cm) nodal lesion, or one bi-dimensionally measurable (≥1 cm) extranodal lesion, as measured on CT scan)

▸ ECOG 0-2

▸ Adequate hematologic function:

Hemoglobin ≥9.0 g/dL (≥90 g/L)
ANC ≥ 1.0 × 109/L (≥1000/μL)
Platelet count ≥75 × 109/L (≥75,000/μL) without a transfusion in the week prior to starting study treatment

▸ Adequate renal function, defined as an estimated CrCl ≥30 mL/min

Key Exclusion Criteria

Any of the following abnormal laboratory values (unless abnormal laboratory values are associated with the underlying lymphoma per the investigator) will exclude the patients

▸ Liver Function

AST or ALT >2.5 × upper limit of normal (ULN)
Total bilirubin ≥1.5 × ULN
Patients with documented Gilbert disease may be enrolled if the total bilirubin is ≤3 × ULN

▸ Coagulation profile

INR or PT >1.5 × ULN (or quick percentage <70%, if Quick % used in lieu of time-based units*) in the absence of therapeutic anticoagulation
PTT or aPTT >1.5 × ULN in the absence of therapeutic anticoagulation or a lupus anticoagulant

▸ Peripheral neuropathy assessed to be Grade >1 according to NCI CTCAE v5.0 at enrollment

⊳ Prior Treatment

▸ Prior treatment with:

Glofitamab or other bispecific antibodies targeting both CD20 and CD3
R-GemOx or GemOx

▸ Prior solid organ transplantation

▸ Prior allogeneic stem cell transplant

▸ Adverse events from prior anti-cancer therapy that have not resolved to Grade 1 or better as per NCI CTCAE v5.0 (with the exception of alopecia and anorexia).

⊳ Prior Treatment & Time Period

▸ Treatment with radiotherapy, chemotherapy, immunotherapy, immunosuppressive therapy, or any investigational agent for the purposes of treating cancer within 2 weeks prior to first study treatment

▸ Treatment with monoclonal antibodies for the purposes of treating cancer within 4 weeks prior to first study treatment

▸ Recent major surgery (within 4 weeks before the first study treatment) other than for diagnosis

▸ Prior treatment with systemic immunosuppressive medications (including, but not limited to, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents), within 4 weeks prior to first dose of study treatment

▸ Corticosteroid therapy within 2 weeks prior to first dose of study treatment with some exceptions.

⊳ Treatment with immunosuppressives or corticosteroids

▸ Corticosteroid therapy within 2 weeks prior to first dose of study treatment, with the following exceptions:

Corticosteroid treatment ≤10 mg/day prednisone or equivalent within 2 weeks prior to the first dose of study treatment is permitted-
Administration of acute, low-dose corticosteroids to treat cancer symptoms or side effects of treatment (e.g., single dose of dexamethasone for nausea or B‐symptoms) is permitted.
The use of inhaled corticosteroids is permitted
The use of mineralocorticoids for management of orthostatic hypotension is permitted
The use of physiologic doses of corticosteroids for management of adrenal insufficiency is permitted

⊳ Infection Related

▸ Known active infection (bacterial, viral, fungal, mycobacterial, parasitic, or other) at study enrollment or any major episode of infection (as per the investigator) within 4 weeks prior to the first study treatment

▸ Suspected or latent tuberculosis (confirmed by positive interferon-γ release assay)

▸ Known history of :

HIV seropositive status
PML (Progressive multifocal leukoencephalopathy)

▸ Known or suspected chronic active Epstein-Barr viral infection

▸ Positive HBV infection (positive HBsAg serology)

Patients with occult or prior HBV infection (defined as negative HBsAg and positive HBcAb) may be included if HBV DNA is undetectable, and they are willing to undergo DNA testing during study and up to 12 months after the last cycle of study treatment.

▸ Positive HCV antibody (Eligible if negative PCR HCV RNA)

⊳ Medical History Related

▸ Current or history of CNS disease, such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease

Patients with a history of stroke who have not experienced a stroke or transient ischemic attack within the past 2 years and have no residual neurologic deficits, as judged by the investigator, are allowed.

▸ Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results, including:

Significant & extensive* cardiovascular disease (such as New York Heart Association Class III or IV cardiac disease or Objective Assessment Class C or D*, myocardial infarction within the last 3 months, unstable arrhythmias, or unstable angina) or significant pulmonary disease (including obstructive pulmonary disease)

▸ Known or suspected history of hemophagocytic lymphohistiocytosis (HLH)

▸ Clinically significant history of cirrhotic liver disease

▸ Autoimmune disease

Patients with a history of autoimmune hepatitis, systemic lupus erythematosus, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener granulomatosis, Sjögren syndrome, multiple sclerosis, or glomerulonephritis will be excluded.
Patients with a history of immune thrombocytopenic purpura, autoimmune hemolytic anemia, Guillain-Barré syndrome, myasthenia gravis, myositis, rheumatoid arthritis, vasculitis, or other autoimmune diseases will be excluded unless they have not required systemic therapy in the last 12 months.
Patients with history of autoimmune-related hypothyroidism on a stable dose of thyroid-replacement hormone maybe eligible
Patients with controlled Type 1 diabetes mellitus who are on an insulin regimen are eligible for the study

▸ History of other malignancy that could affect compliance with the protocol or interpretation of results with following exceptions:

Patients with a history of curatively treated basal or squamous cell carcinoma of the skin or in situ carcinoma of the cervix at any time prior to the study are eligible
Patients with low-grade, early-stage prostate cancer (Gleason score 6 or below, Stage 1 or 2) with no requirement for therapy at any time prior to study are eligible
Patients with any other malignancy appropriately treated with curative intent and the malignancy has been in remission without treatment for ≥2 years prior to enrollment are eligible
Patients receiving adjuvant endocrine therapy for non-metastatic, hormone receptor-positive breast cancer for > 2 years prior enrollment are eligible

⊳ Pregnancy/breastfeeding and contraception

▸ Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment or within 18 months after the final dose of study treatment

▸ Women of childbearing potential must have a negative serum pregnancy test result within 7 days prior to initiation of study treatment

▸ Patients must agree to follow appropriate contraceptive measures

⊳ Live vaccine

▸ Administration of a live, attenuated vaccine within 4 weeks before first study treatment administration or anticipation that such a live, attenuated vaccine will be required during the study