Neoplasms

Blood and Lymph Conditions

All Conditions

Immune System Diseases

Heart and Blood Diseases

Symptoms and General Pathology

Rare Diseases

Leukemia

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Lymphoma

Multiple Myeloma

Neoplasms, Plasma Cell

Hematologic Neoplasms

Leukemia, Lymphocytic, Chronic, B-Cell

Neoplasm, Residual

Neoplasms by Histologic Type

Hematologic Diseases

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hemorrhagic Disorders

Lymphoproliferative Disorders

Immunoproliferative Disorders

Lymphatic Diseases

Leukemia, B-Cell

Chronic Disease

Disease Attributes

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Chronic Graft Versus Host Disease

Lymphosarcoma

Chronic Lymphocytic Leukemia

Acute Graft Versus Host Disease

patients diagnosed with acute lymphoblastic leukemia

patients diagnosed with chronic lymphocytic leukemia

patients diagnosed with non-Hodgkin lymphoma

minimal residual disease (MRD) assay using blood, bone marrow, or other tissue containing tumor cells

clonoSEQ Assay

Heidi Simmons, PhD

This is a prospective, multicenter, observational study of adult patients with a diagnosis of acute lymphoblastic leukemia (ALL), multiple myeloma (MM), chronic lymphocytic leukemia (CLL), or non-Hodgkin lymphoma (NHL). This study will enroll up to 528 patients in up to 50 sites in the United States and collect data with regard to use of the clonoSEQ MRD assay in the management of lymphoid malignancies.

Data show that detection of MRD may be important to guide treatment decisions in ALL, MM, CLL, and NHL. However, there remains a lack of real-world evidence for making therapeutic decisions based upon MRD status. This study is designed to understand when in a patient's treatment continuum the assay is used and how clonoSEQ MRD data impact the treatment decisions made by investigators.

All patients enrolled in the study will be followed for at least 2 yrs. Demographic data and disease status will be captured at study enrollment. Patients must be \>/= 18 yrs of age and able to sign informed consent. A given patient is eligible to enroll in the study if the treating physician has made the decision to use the clonoSEQ assay as part of that patient's routine cancer care. Reasons for placing a clonoSEQ order and subsequent decisions made as a result of MRD data will be tracked. Patient treatment will also be tracked over the course of the study in order to understand how clonoSEQ use is incorporated into current treatment regimens.

Participating centers will include sites that actively use clonoSEQ to manage their patients with lymphoid malignancies.

Remaining samples will be stored for potential use in future assay development research.

The clonoSEQ® Watch Registry

Real World Observational Study Using clonoSEQ® Next Generation Sequencing in Hematologic Malignancies: The 'Watch' Registry

Data will be collected to determine how the clonoSEQ Assay is used as part of routine disease response assessments in lymphoid malignancy patients

Data will be collected to assess the following, as applicable, depending upon distribution of patients that enroll in this study:

* Response to treatment, duration of response, time to next therapy, duration of maintenance therapy, and survival
* Numbers of patients who proceed to transplant in the ALL and MM cohorts

Data will be collected to determine at what points lymphoid malignancy patients are in their treatment continuums when the clonoSEQ Assay is used to monitor MRD levels

Data will be collected with regard to changes to treatment/drug regimens in order to determine how clonoSEQ Assay MRD results inform and impact routine clinical practice

Adaptive Biotechnologies

Lymphoma, Mantle-Cell

Lymphoma, Non-Hodgkin

Mantle Cell Lymphoma

All Drugs and Chemicals

Antineoplastic Agents

Amino Acids

Antibodies

Antibodies, Monoclonal

Obinutuzumab

Immunoglobulins

Pirtobrutinib

Muromonab-CD3

Antineoplastic Agents, Immunological

Immunoglobulins, Intravenous

Antibodies, Bispecific

Immunologic Factors

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Participants receive obinutuzumab IV on days 1 and 2 of cycle 1 for a total of 2 doses. Participants receive glofitamab IV on days 8 and 15 of cycle 1 and day 1 of remaining cycles. Cycles repeat every 21 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Participants receive pirtobrutinib PO once a day (QD) on days 1-21. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity. Participants also undergo FDG-PET/CT at screening, after every 4 cycles through cycle 13 and then after every 6 cycles. Participants will undergo a bone marrow biopsy and aspiration at cycle 13 and blood sample collection throughout study and a tissue biopsy at relapse or progression.

Glofitamab

Tumor Imaging

Biospecimen Collection

ClonoSEQ is an FDA-cleared, Clinical Laboratory Improvement Amendments of 1988 (CLIA)-validated measure used to determine minimal residual disease (MRD). This helps uncover how much, if any, cancer remains in your body during and after treatment.

ClonoSeq Assay

Undergo bone marrow biopsy and aspiration.

Bone Marrow Biopsy

Morgan Tate

C. Babis Andreadis, MD

This phase II trial tests the safety and effectiveness of glofitamab given in combination with pirtobrutinib in treating patients with mantle cell lymphoma that has come back after a period of improvement (relapsed) or that has not responded to previous treatment (refractory). Glofitamab and obinutuzumab are monoclonal antibodies that may interfere with the ability of cancer cells to grow and spread. Obinutuzumab may also reduce the risk of immune-related conditions from treatment. Pirtobrutinib is in a class of medications called kinase inhibitors. It works by blocking the action of the protein that signals cancer cells to multiply. Giving glofitamab in combination with pirtobrutinib may be safe, tolerable and/or effective in treating patients with relapsed or refractory mantle cell lymphoma.

PRIMARY OBJECTIVES:

I. To characterize the safety and tolerability of the combination of glofitamab and pirtobrutinib in the first six patients enrolled.

II. To evaluate the preliminary efficacy of glofitamab and pirtobrutinib in patients with relapsed or refractory mantle cell lymphoma (MCL) as measured by complete response rate.

SECONDARY OBJECTIVES:

I. To evaluate the preliminary efficacy of glofitamab and pirtobrutinib in patients with relapsed or refractory MCL as measured by progression-free survival and overall survival.

II. To characterize the magnitude and duration of anti-tumor activity by objective response rate and duration of response.

III. To characterize the safety and tolerability of the combination of glofitamab and pirtobrutinib.

IV. To evaluate the preliminary efficacy of glofitamab and pirtobrutinib in patients with relapsed or refractory MCL as measured by complete response without measurable disease (CRMRD-) rate.

V. To evaluate the time-to-complete response without measurable residual disease (CRMRD-).

VI. To evaluate the treatment-free interval among patients who discontinue treatment following CRMRD- status.

EXPLORATORY OBJECTIVES:

I. To explore associations between baseline tumor characteristics including genetic (e.g. mutations in BTK) and immune profiles (e.g. expression of co-inhibitory receptors and T cell phenotypes) and outcomes in patients administered the combination of glofitamab and pirtobrutinib.

II. To explore the effects of the combination of glofitamab and pirtobrutinib on pharmacodynamic markers relating to drug mechanism (e.g. emergence of clones with mutations conferring resistance to the study combination).

III. To estimate the quality of life of participants during therapy with glofitamab and pirtobrutinib.

IV. To explore time-to-CRMRD- during therapy with glofitamab and pirtobrutinib.

OUTLINE:

Patients receive obinutuzumab intravenously (IV) on days 1 and 2 of cycle 1 for a total of 2 doses. Patients receive glofitamab IV on days 8 and 15 of cycle 1 and day 1 of remaining cycles. Cycles repeat every 21 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients receive pirtobrutinib orally (PO) once daily (QD) on days 1-21. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo fludeoxyglucose F-18 (FDG)-positron emission tomography (PET)/computed tomography (CT) at screening, after every 4 cycles through cycle 13 and then after every 6 cycles. Patients additionally undergo echocardiography (ECHO) or multigated acquisition scan (MUGA) at screening, a bone marrow biopsy and aspiration at cycle 13 and blood sample collection at screening and throughout study. Additionally, patients may undergo a tissue biopsy at relapse or progression.

After completion of study treatment, patients are followed up every 3 months for up to 2 years from the start of treatment.

Glofitamab With Pirtobrutinib for Relapsed or Refractory Mantle Cell Lymphoma

A Multicenter Phase 2 Study of Glofitamab With Pirtobrutinib for Relapsed or Refractory Mantle Cell Lymphoma

The severity of the toxicities will be graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0. AEs and clinically significant laboratory abnormalities meeting grade 3 4 or 5 will be summarized by maximum intensity and relationship to study drug.

CR will be defined as the proportion of treated participants who experience a CR per Lugano criteria among evaluable participants. The Lugano classification recommends the Deauville five-point scale for reporting response by FDG PET-CT: (1) no uptake or no residual uptake (when used interim) (2) slight uptake, but below blood pool (mediastinum) (3) uptake above mediastinal, but below or equal to uptake in the liver (4) uptake slightly to moderately higher than liver (5) markedly increased uptake or any new lesion (on response evaluation).

PFS will be defined as the time that elapses between initiation of trial therapy and the earlier of the day of first documented disease progression or death from any cause. Progression is defined by Lugano criteria of (1) new or increased adenopathy; an individual node must be abnormal with: (a) longest transverse diameter (LDi) \>1.5 cm AND (2) splenic volume increase (3) new or larger non-measured lesions (4) recurrent previously resolved lesions (5) new extranodal lesion \>1 cm in any axis (new lesions \<1 cm in any axis are included if these are "unequivocally attributable" to lymphoma) (6) a new node \>1.5 cm in any axis . PFS will be summarized using Kaplan-Meier method.

OS will be defined as the time that elapses between the initiation of trial therapy and the date of death from any cause for all evaluable participants. OS will be summarized using Kaplan-Meier method.

OR will be defined as the proportion of treated patients who experience an objective response (CR or partial response (PR) per Lugano criteria) among evaluable patients.

DOR will be defined as the time that elapses between the day of first documented response to trial therapy (CR or PR, whichever is first recorded) and subsequent disease progression.

CRMRD will be defined as the achievement of =\< 1 x 10-6 malignant cells in peripheral blood, as assessed by ClonoSEQ assay in a participant who meets all other criteria for CR.

Time to CRMRD will calculate the time that elapses between the initiation of trial therapy and the day of first documented CRMRD and summarized using Kaplan-Meier method.

Treatment-free interval will be defined as the time that elapses from CRMRD status to the time of recurrence and summarized using Kaplan-Meier method.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
The clonoSEQ® Watch Registry	NCT04545333	Acute Lymphobla... Chronic Lymphoc... Multiple Myelom... Non-hodgkin Lym...	clonoSEQ Assay	18 Years -	Adaptive Biotechnologies
Glofitamab With Pirtobrutinib for Relapsed or Refractory Mantle Cell Lymphoma	NCT06252675	Mantle Cell Lym...	Obinutuzumab Glofitamab Pirtobrutinib Tumor Imaging Biospecimen Col... ClonoSeq Assay Bone Marrow Bio...	18 Years -	University of California, San Francisco
Glofitamab With Pirtobrutinib for Relapsed or Refractory Mantle Cell Lymphoma	NCT06252675	Mantle Cell Lym...	Obinutuzumab Glofitamab Pirtobrutinib Tumor Imaging Biospecimen Col... ClonoSeq Assay Bone Marrow Bio...	18 Years -	University of California, San Francisco
The clonoSEQ® Watch Registry	NCT04545333	Acute Lymphobla... Chronic Lymphoc... Multiple Myelom... Non-hodgkin Lym...	clonoSEQ Assay	18 Years -	Adaptive Biotechnologies

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