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ACTIVE NOT RECRUITING

NCT03984448

PHASE2/PHASE3

Testing the Addition of a New Anti-cancer Drug, Venetoclax, to Usual Chemotherapy for High Grade B-cell Lymphomas

Sponsor: National Cancer Institute (NCI)

View on ClinicalTrials.gov

Summary

This phase II/III trial tests whether it is possible to decrease the chance of high-grade B-cell lymphomas returning or getting worse by adding a new drug, venetoclax to the usual combination of drugs used for treatment. Venetoclax may stop the growth of cancer cells by blocking a protein called Bcl-2. Drugs used in usual chemotherapy, such as rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone, and etoposide, 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. Giving venetoclax together with usual chemotherapy may work better than usual chemotherapy alone in treating patients with high-grade B-cell lymphomas, and may increase the chance of cancer going into remission and not returning.

Official title: Randomized Phase II/III Study of Venetoclax (ABT199) Plus Chemoimmunotherapy for MYC/BCL2 Double-Hit and Double Expressing Lymphomas

Key Details

Gender

All

Age Range

18 Years - 80 Years

Study Type

INTERVENTIONAL

Enrollment

363

Start Date

2019-10-22

Completion Date

2028-08-13

Last Updated

2026-10-26

Healthy Volunteers

Conditions

Diffuse Large B-Cell Lymphoma Diffuse Large B-Cell Lymphoma, Not Otherwise Specified Double-Expressor Lymphoma EBV-Positive Diffuse Large B-Cell Lymphoma, Not Otherwise Specified High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 Rearrangements High Grade B-Cell Lymphoma, Not Otherwise Specified Neoplastic Cells With Double Expression of MYC and BCL2 Proteins Present Transformed Indolent B-Cell Non-Hodgkin Lymphoma to Diffuse Large B-Cell Lymphoma

Interventions

PROCEDURE

Biospecimen Collection

Undergo blood sample collection

PROCEDURE

Bone Marrow Biopsy

Undergo bone marrow biopsy

PROCEDURE

Computed Tomography

Undergo CT scan

DRUG

Cyclophosphamide

Given IV

DRUG

Doxorubicin Hydrochloride

Given IV

DRUG

Etoposide

Given IV

PROCEDURE

Lumbar Puncture

Undergo lumbar puncture

PROCEDURE

Positron Emission Tomography

Undergo PET scan

DRUG

Prednisone

Given PO

BIOLOGICAL

Rituximab

Given IV

DRUG

Venetoclax

Given PO

DRUG

Vincristine Sulfate

Given IV

Inclusion Criteria: * Pathologic diagnosis of diffuse large B-cell lymphoma (DLBCL) or high grade B-cell lymphoma not otherwise specified (HGBCL not otherwise specified \[NOS\]). Eligible subtypes include DLBCL NOS, Epstein Barr Virus positive (EBV+) DLBCL, HGBCL NOS and DLBCL/HGBCL transformed from an underlying indolent B-cell lymphoma. Patients with T-cell/histiocyte rich large B-cell lymphoma and primary mediastinal B-cell lymphoma are not eligible * Double hit lymphoma (DHL) or double expressing lymphoma (DEL) * DHL is defined as high grade B-cell lymphoma with one of the below: * Translocations of MYC and BCL2 * Translocations of MYC and BCL2 and BCL6 (triple hit lymphoma) * Translocations of MYC and BCL6 without BCL2 translocation BUT with immunohistochemistry (IHC) expression of BCL2 (\>=50%) * DEL is defined as DLBCL or high grade B-cell lymphoma not otherwise specified (NOS) with protein expression by IHC of both MYC (\>= 40%) and BCL2 (\>= 50%) in the absence of dual translocations of both MYC and BCL2 and/or BCL6). (Double Expressing Lymphoma, DEL). Local determination of fluorescence in situ hybridization (FISH) and IHC will be performed per standardized guidelines and will be acceptable for study entry, but local IHC and FISH results for MYC must be submitted for central review in order to determine eligibility if enrolling as DEL based on local results during phase II. Central pathology review is no longer required as of Update #03. * The diagnosis of DLBCL/HGBCL and assessment of DEL/DHL will be performed per standardized guidelines at local institutions and patients will be enrolled based on local determination. Cases submitted as DHL must demonstrate the presence of a MYC translocation as well as a translocation of BCL2, BCL6, or both. Cases submitted as a DEL must demonstrate appropriate IHC protein expression of MYC and BCL2, and be negative for translocations of MYC along with translocations of BCL2 and/or BCL6 by FISH. Patients with MYC translocations and no translocations of either BCL2 or BCL6 are eligible for the DEL cohort * Patients must have FDG-avid disease on PET/CT * No prior treatment for DLBCL/HGBCL is allowed with the exception of corticosteroids administered for palliation, or a single cycle of either rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or dose adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (DA-EPOCH-R) administered prior to enrollment. Corticosteroids or local radiation therapy are also allowed. Patients may have received intrathecal chemotherapy for CNS prophylaxis prior to registration. This single pre-registration cycle is being allowed to facilitate enrolling patients who required immediate initiation of therapy for rapidly progressing disease, or for patients where FISH or IHC results returned after initiation of chemotherapy rendered them protocol eligible. Patients with DLBCL or HGBCL transformed from an underlying indolent lymphoma cannot have received prior chemotherapy, but prior anti-CD20 monoclonal antibody therapy or radiation therapy for an indolent B-cell lymphoma is allowed. * Not pregnant and not nursing, because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown. Therefore, for women of childbearing potential only, a negative pregnancy test done =\< 14 days prior to registration is required. * Age 18 - 80 years * Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2. * Absolute neutrophil count (ANC) \>= 1,000/mm\^3. * Unless attributable to lymphoma. * Platelet count \>= 100,000/mm\^3. * Unless attributable to lymphoma. * Creatinine =\< 1.5 mg/dL OR calculated (calc.) creatinine clearance \>= 50 mL/min. * Unless attributable to lymphoma. * Total bilirubin =\< 2.0 mg/dL. * Unless attributable to lymphoma. * Unless attributable to Gilbert's disease. * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 3 times institution upper limit of normal (ULN). * Unless attributable to lymphoma. * Archival tissue must be available for submission in all patients for histopathology review, though participation in correlative substudies is optional. * No active ischemic heart disease or congestive heart failure, and left ventricular ejection fraction (LVEF) \>= 45%. * No known active human immunodeficiency virus (HIV) disease. Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial. * No known lymphomatous involvement of the central nervous system (CNS). A lumbar puncture or neuroimaging prior to study enrollment is not required in the absence of neurological signs or symptoms concerning for CNS involvement. * No active hepatitis B or hepatitis C infection. Patients with prior hepatitis B virus (HBV) exposure (positive HBV core antibody and/or surface antigen) are eligible if they have no detectable viral load, and are taking appropriate prophylactic antiviral therapy to prevent reactivation. Patients with history of hepatitis C virus (HCV) are eligible if they have been treated for HCV and have an undetectable HCV viral load. * Chronic concomitant treatment with strong inhibitors of CYP3A4 is not allowed on this study. Patients on strong CYP3A4 inhibitors must discontinue the drug for 14 days prior to initiation of venetoclax. * Chronic concomitant treatment with strong CYP3A4 inducers is not allowed. Patients must discontinue the drug 14 days prior to the start of venetoclax.

Locations (634)

University of Alabama at Birmingham Cancer Center

Birmingham, Alabama, United States

Anchorage Associates in Radiation Medicine

Anchorage, Alaska, United States

Anchorage Radiation Therapy Center

Anchorage, Alaska, United States

Alaska Breast Care and Surgery LLC

Anchorage, Alaska, United States

Alaska Oncology and Hematology LLC

Anchorage, Alaska, United States

Alaska Women's Cancer Care

Anchorage, Alaska, United States

Anchorage Oncology Centre

Anchorage, Alaska, United States

Katmai Oncology Group

Anchorage, Alaska, United States

Providence Alaska Medical Center

Anchorage, Alaska, United States

Fairbanks Memorial Hospital

Fairbanks, Alaska, United States

Cancer Center at Saint Joseph's

Phoenix, Arizona, United States

Mercy Hospital Fort Smith

Fort Smith, Arkansas, United States

CHI Saint Vincent Cancer Center Hot Springs

Hot Springs, Arkansas, United States

Mission Hope Medical Oncology - Arroyo Grande

Arroyo Grande, California, United States

Providence Saint Joseph Medical Center/Disney Family Cancer Center

Burbank, California, United States

Community Cancer Institute

Clovis, California, United States

University Oncology Associates

Clovis, California, United States

Loma Linda University Medical Center

Loma Linda, California, United States

Fremont - Rideout Cancer Center

Marysville, California, United States

University of California Davis Comprehensive Cancer Center

Sacramento, California, United States

UCSF Medical Center-Parnassus

San Francisco, California, United States

Pacific Central Coast Health Center-San Luis Obispo

San Luis Obispo, California, United States

Mission Hope Medical Oncology - Santa Maria

Santa Maria, California, United States

Gene Upshaw Memorial Tahoe Forest Cancer Center

Truckee, California, United States

Rocky Mountain Cancer Centers-Aurora

Aurora, Colorado, United States

The Medical Center of Aurora

Aurora, Colorado, United States

Boulder Community Foothills Hospital

Boulder, Colorado, United States

Rocky Mountain Cancer Centers-Boulder

Boulder, Colorado, United States

Rocky Mountain Cancer Centers - Centennial

Centennial, Colorado, United States

Penrose-Saint Francis Healthcare

Colorado Springs, Colorado, United States

Rocky Mountain Cancer Centers-Penrose

Colorado Springs, Colorado, United States

Cancer Center of Colorado at Sloan's Lake

Denver, Colorado, United States

National Jewish Health-Main Campus

Denver, Colorado, United States

The Women's Imaging Center

Denver, Colorado, United States

AdventHealth Porter

Denver, Colorado, United States

Colorado Blood Cancer Institute

Denver, Colorado, United States

Presbyterian - Saint Lukes Medical Center - Health One

Denver, Colorado, United States

Rocky Mountain Cancer Centers-Midtown

Denver, Colorado, United States

Saint Joseph Hospital - Cancer Centers of Colorado

Denver, Colorado, United States

Rocky Mountain Cancer Centers-Rose

Denver, Colorado, United States

Rose Medical Center

Denver, Colorado, United States

Western Surgical Care

Denver, Colorado, United States

CommonSpirit Cancer Center Mercy

Durango, Colorado, United States

Mercy Medical Center

Durango, Colorado, United States

Mountain Blue Cancer Care Center - Swedish

Englewood, Colorado, United States

Rocky Mountain Cancer Centers - Swedish

Englewood, Colorado, United States

Swedish Medical Center

Englewood, Colorado, United States

The Melanoma and Skin Cancer Institute

Englewood, Colorado, United States

National Jewish Health-Western Hematology Oncology

Golden, Colorado, United States

Saint Mary's Hospital and Regional Medical Center

Grand Junction, Colorado, United States

Banner North Colorado Medical Center

Greeley, Colorado, United States

Good Samaritan Hospital - Cancer Centers of Colorado

Lafayette, Colorado, United States

CommonSpirit Saint Anthony Hospital Cancer Center

Lakewood, Colorado, United States

Rocky Mountain Cancer Centers-Lakewood

Lakewood, Colorado, United States

Rocky Mountain Cancer Centers-Littleton

Littleton, Colorado, United States

AdventHealth Littleton

Littleton, Colorado, United States

Rocky Mountain Cancer Centers-Sky Ridge

Lone Tree, Colorado, United States

Sky Ridge Medical Center

Lone Tree, Colorado, United States

Longmont United Hospital

Longmont, Colorado, United States

Rocky Mountain Cancer Centers-Longmont

Longmont, Colorado, United States

Banner North Colorado Medical Center - Loveland Campus

Loveland, Colorado, United States

AdventHealth Parker

Parker, Colorado, United States

Saint Mary Corwin Medical Center

Pueblo, Colorado, United States

National Jewish Health-Northern Hematology Oncology

Thornton, Colorado, United States

Rocky Mountain Cancer Centers-Thornton

Thornton, Colorado, United States

Intermountain Health Lutheran Hospital

Wheat Ridge, Colorado, United States

Beebe Medical Center

Lewes, Delaware, United States

Beebe South Coastal Health Campus

Millville, Delaware, United States

Delaware Clinical and Laboratory Physicians PA

Newark, Delaware, United States

Helen F Graham Cancer Center

Newark, Delaware, United States

Medical Oncology Hematology Consultants PA

Newark, Delaware, United States

Christiana Care Health System-Christiana Hospital

Newark, Delaware, United States

Beebe Health Campus

Rehoboth Beach, Delaware, United States

TidalHealth Nanticoke / Allen Cancer Center

Seaford, Delaware, United States

Christiana Care Health System-Wilmington Hospital

Wilmington, Delaware, United States

Holy Cross Hospital

Fort Lauderdale, Florida, United States

Cleveland Clinic-Weston

Weston, Florida, United States

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia, United States

Emory Saint Joseph's Hospital

Atlanta, Georgia, United States

Memorial Health University Medical Center

Savannah, Georgia, United States

Summit Cancer Care-Memorial

Savannah, Georgia, United States

Island Urology-Hilo

Hilo, Hawaii, United States

Hawaii Cancer Care Inc - Waterfront Plaza