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RECRUITING

NCT04546399

PHASE2

A Study to Compare Blinatumomab Alone to Blinatumomab With Nivolumab in Patients Diagnosed With First Relapse B-Cell Acute Lymphoblastic Leukemia (B-ALL)

Sponsor: National Cancer Institute (NCI)

View on ClinicalTrials.gov

Summary

This phase II trial studies the effect of nivolumab in combination with blinatumomab compared to blinatumomab alone in treating patients with B-cell acute lymphoblastic leukemia (B-ALL) that has come back (relapsed). Down syndrome patients with relapsed B-ALL are included in this study. Blinatumomab is an antibody, which is a protein that identifies and targets specific molecules in the body. Blinatumomab searches for and attaches itself to the cancer cell. Once attached, an immune response occurs which may kill the cancer cell. Nivolumab is a medicine that may boost a patient's immune system. Giving nivolumab in combination with blinatumomab may cause the cancer to stop growing for a period of time, and for some patients, it may lessen the symptoms, such as pain, that are caused by the cancer.

Official title: A Phase 2 Study of Blinatumomab (NSC# 765986) in Combination With Nivolumab (NSC # 748726), a Checkpoint Inhibitor of PD-1, in B-ALL Patients Aged >/= 1 to < 31 Years Old With First Relapse

Key Details

Gender

All

Age Range

1 Year - 30 Years

Study Type

INTERVENTIONAL

Enrollment

461

Start Date

2020-12-17

Completion Date

2028-06-30

Last Updated

2025-09-10

Healthy Volunteers

Conditions

Down Syndrome Recurrent B Acute Lymphoblastic Leukemia

Interventions

RADIATION

3-Dimensional Conformal Radiation Therapy

Undergo 3D-CRT

PROCEDURE

Biospecimen Collection

Undergo blood, urine and cerebrospinal fluid collection

BIOLOGICAL

Blinatumomab

Given IV

PROCEDURE

Bone Marrow Aspiration

Undergo bone marrow aspiration

PROCEDURE

Bone Marrow Biopsy

Undergo bone marrow biopsy

DRUG

Calaspargase Pegol

Given IV

DRUG

Cytarabine

Given IT

DRUG

Dexamethasone

Given PO or IV

DRUG

Hydrocortisone Sodium Succinate

Given IT

PROCEDURE

Lumbar Puncture

Undergo lumbar puncture

DRUG

Mercaptopurine

Given PO

DRUG

Methotrexate

Given IT, PO, and IV

BIOLOGICAL

Nivolumab

Given IV

DRUG

Pegaspargase

Given IM or IV

DRUG

Pegcrisantaspase

Given IM or IV

DRUG

Vincristine Sulfate

Given IV push or via infusion

Inclusion Criteria: * Patients must be \>= 1 and \< 31 years at time of enrollment * Patients must have first relapse of CD19+ B-ALL (relapse blasts must express CD19) in one of the following categories: * Isolated bone marrow relapse * Isolated central nervous system (CNS) (excluding known optic nerve/retinal and CNS chloromas) and/or testicular relapse * Combined bone marrow with extramedullary relapse in the CNS (excluding known optic nerve/retinal and CNS chloromas) and/or testes * Patients with Down syndrome (DS) are eligible in the following categories: * Isolated bone marrow relapse * Combined bone marrow with CNS (excluding known optic nerve/retinal and CNS chloromas) and/or testicular relapse * Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2. Use Karnofsky for patients \> 16 years of age and Lansky for patients =\< 16 years of age * Of note, for patients with developmental delay (e.g., Down syndrome) regardless of age, Lansky scale may be substituted for Karnofsky scale. However, the requirement for ECOG 0-2 remains, regardless of known history of developmental delay * Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study * Patients with prior blinatumomab or CD19+ chimeric antigen receptor therapy in the upfront setting will be eligible, provided relapsed lymphoblasts retain CD19 expression * Patients must not have had a prior hematopoietic stem cell transplant * A single intrathecal chemotherapy at the time of relapse will be allowed. If \< 7 days have elapsed between this intrathecal therapy (IT) and the start of protocol therapy, then the day 1 intrathecal chemotherapy (i.e. methotrexate, cytarabine, or triple intrathecal) may be omitted * In the 28 days prior to enrollment, up to five days of post-relapse, pre-enrollment therapy (steroids and/or hydroxyurea only) is permissible * Patients with Down syndrome who received pre-enrollment therapy and have a white blood count (WBC) \>= 30,000/ul at the time of enrollment still must receive protocol specified cytoreductive therapy with vincristine and dexamethasone, and no "washout" is required * Patients with Down syndrome who received pre-enrollment therapy and have a WBC \< 30,000/ul at the time of enrollment must be given a 24 hour "washout" before starting immunotherapy * Note: There is no waiting period or "washout" for patients who relapse while receiving upfront therapy * Creatinine clearance or radioisotope glomerular filtration rate (GFR) \>= 70 mL/min/1.73 m\^2 OR a serum creatinine based on age/sex as follows (within 7 calendar days prior to enrollment): * Age: Maximum serum creatinine (mg/dL) * 1 to \< 2 years: 0.6 (male), 0.6 (female) * 2 to \< 6 years: 0.8 (male), 0.8 (female) * 6 to \< 10 years: 1 (male), 1 (female) * 10 to \< 13 years: 1.2 (male), 1.2 (female) * 13 to \< 16 years: 1.5 (male), 1.4 (female) * \>= 16 years: 1.7 (male), 1.4 (female) * The threshold creatinine values in this Table were derived from the Schwartz formula for estimating GFR utilizing child length and stature data published by the Center for Disease Control (CDC) * Shortening fraction of \>= 27% by echocardiogram, or ejection fraction of \>= 50% by echocardiogram, cardiac magnetic resonance imaging (MRI) or radionuclide angiogram * No evidence of dyspnea at rest, no exercise intolerance, and a pulse oximetry \> 94% if there is clinical indication for determination * All patients and/or their parents or legal guardians must sign a written informed consent * All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met Exclusion Criteria: * Patients with B-lymphoblastic lymphoma (B-LLy) * Patients with Burkitt leukemia/lymphoma or mature B-cell leukemia * Patients with Philadelphia chromosome positive (Ph+) B-ALL * Patients with mixed phenotype acute leukemia (MPAL) * Patients with known Charcot-Marie-Tooth disease * Patients with known MYC translocation associated with mature (Burkitt) B-cell ALL, regardless of blast immunophenotype * Patients with active, uncontrolled infection defined as: * Positive bacterial blood culture within 48 hours of study enrollment * Receiving IV or PO antibiotics for an infection with continued signs or symptoms. Note: Patients may be receiving IV or oral antibiotics to complete a course of therapy for a prior documented infection if cultures have been negative for at least 48 hours and signs or symptoms of active infection have resolved. For patients with clostridium (C.) difficile diarrhea, at least 72 hours of antibacterial therapy must have elapsed and stools must have normalized to baseline. * Fever above 38.2 degrees Celsius (C) within 48 hours of study enrollment with clinical signs of infection. Fever without clinical signs of infection that is attributed to tumor burden is allowed if blood cultures are negative for \> 48 hours * A positive fungal culture within 30 days of study enrollment or active therapy for presumed invasive fungal infection * Active viral or protozoal infection requiring IV treatment * Patients known to have one of the following concomitant genetic syndromes: Bloom syndrome, ataxia-telangiectasia, Fanconi anemia, Kostmann syndrome, Shwachman syndrome or any other known bone marrow failure syndrome are not eligible. * Patients with uncontrolled HIV, hepatitis B, or hepatitis C infection. Of note, patients with known human immunodeficiency virus (HIV) infection on effective anti-retroviral therapy with undetectable viral load for at least the last 6 months prior to enrollment are eligible. Similarly, hepatitis B and hepatitis C positive patients who have been treated and have no viral detectable burden are also eligible * Patients with significant central nervous system pathology that would preclude treatment with blinatumomab, including history of severe neurologic disorder or autoimmune disease with CNS involvement * Note: Patients with a history of seizures that are well controlled on stable doses of anti-epileptic drugs are eligible Patients with a history of cerebrovascular ischemia/hemorrhage with residual deficits are not eligible. Patients with a history of cerebrovascular ischemia/hemorrhage remain eligible provided all neurologic deficits have resolved * Patients with an active known/suspected autoimmune disease are not eligible. However, patients with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll * Group 4 and patients with DS patients with known non-hematopoietic, non-CNS/testicular extramedullary disease (i.e., chloromatous disease) are not eligible * Note: Group 3 patients with known non-hematopoietic, non-CNS/testicular extramedullary disease (i.e., chloromatous disease) are eligible if this is NOT the only site of relapsed disease * Female patients of childbearing potential are not eligible unless a negative pregnancy test result has been obtained within 7 days prior to enrollment. Patients who are sexually active and of reproductive potential are not eligible unless they agree to use an effective contraceptive method for the duration of this study. Men with female partners of childbearing potential should use effective contraception during the duration of their treatment. The effect of blinatumomab on fertility has not been evaluated. Blinatumomab is not recommended for pregnant women or women of childbearing potential (WOCBP) not using contraception. Females of reproductive potential must use effective contraception during treatment and for at least 48 hours after the last dose of blinatumomab. Studies in animal models have shown that nivolumab can adversely impair pregnancy. Thus, nivolumab is expected to cause fetal harm during pregnancy. WOCBP receiving nivolumab must continue contraception for a period of at least 5 months after the last dose of nivolumab. It is unknown whether nivolumab is present in breast milk, thus breastfeeding should be discontinued while a patient is receiving nivolumab * Lactating females are not eligible unless they agree to not breastfeed their infants. It is unknown whether blinatumomab or its metabolites are excreted in human breast milk. Women are not permitted to breastfeed while receiving blinatumomab and for the last 48 hours after the last blinatumomab dose. Due to the potential for serious adverse reactions in the breastfed infant, women are not permitted to breastfeed during treatment and for 5 months after the last nivolumab dose

Locations (215)

Children's Hospital of Alabama

Birmingham, Alabama, United States

USA Health Strada Patient Care Center

Mobile, Alabama, United States

Providence Alaska Medical Center

Anchorage, Alaska, United States

Kingman Regional Medical Center

Kingman, Arizona, United States

Banner Children's at Desert

Mesa, Arizona, United States

Phoenix Childrens Hospital

Phoenix, Arizona, United States

Banner University Medical Center - Tucson

Tucson, Arizona, United States

Arkansas Children's Hospital

Little Rock, Arkansas, United States

Kaiser Permanente-Anaheim

Anaheim, California, United States

PCR Oncology

Arroyo Grande, California, United States

Kaiser Permanente-Bellflower

Bellflower, California, United States

Kaiser Permanente Downey Medical Center

Downey, California, United States

City of Hope Comprehensive Cancer Center

Duarte, California, United States

Kaiser Permanente-Fontana

Fontana, California, United States

Loma Linda University Medical Center

Loma Linda, California, United States

Children's Hospital Los Angeles

Los Angeles, California, United States

Kaiser Permanente Los Angeles Medical Center

Los Angeles, California, United States

Cedars Sinai Medical Center

Los Angeles, California, United States

Mattel Children's Hospital UCLA

Los Angeles, California, United States

Valley Children's Hospital

Madera, California, United States

Kaiser Permanente-Oakland

Oakland, California, United States

Children's Hospital of Orange County

Orange, California, United States

Lucile Packard Children's Hospital Stanford University

Palo Alto, California, United States

Sutter Medical Center Sacramento

Sacramento, California, United States

University of California Davis Comprehensive Cancer Center

Sacramento, California, United States

Kaiser Permanente-San Diego Zion

San Diego, California, United States

Rady Children's Hospital - San Diego

San Diego, California, United States

UCSF Medical Center-Mission Bay

San Francisco, California, United States

Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center

Torrance, California, United States

Children's Hospital Colorado

Aurora, Colorado, United States

Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center

Denver, Colorado, United States

Connecticut Children's Medical Center

Hartford, Connecticut, United States

Yale University

New Haven, Connecticut, United States

Alfred I duPont Hospital for Children

Wilmington, Delaware, United States

Children's National Medical Center

Washington D.C., District of Columbia, United States

Golisano Children's Hospital of Southwest Florida

Fort Myers, Florida, United States

University of Florida Health Science Center - Gainesville

Gainesville, Florida, United States

Memorial Regional Hospital/Joe DiMaggio Children's Hospital

Hollywood, Florida, United States

Nemours Children's Clinic-Jacksonville

Jacksonville, Florida, United States

AdventHealth Orlando

Orlando, Florida, United States

Arnold Palmer Hospital for Children

Orlando, Florida, United States

Nemours Children's Hospital

Orlando, Florida, United States

Nemours Children's Clinic - Pensacola

Pensacola, Florida, United States

Sacred Heart Hospital

Pensacola, Florida, United States

Johns Hopkins All Children's Hospital

St. Petersburg, Florida, United States

Tampa General Hospital

Tampa, Florida, United States

Saint Joseph's Hospital/Children's Hospital-Tampa

Tampa, Florida, United States

Saint Mary's Medical Center

West Palm Beach, Florida, United States

Children's Healthcare of Atlanta - Arthur M Blank Hospital

Atlanta, Georgia, United States

Memorial Health University Medical Center

Savannah, Georgia, United States

Kapiolani Medical Center for Women and Children

Honolulu, Hawaii, United States

Saint Luke's Cancer Institute - Boise

Boise, Idaho, United States

Lurie Children's Hospital-Chicago

Chicago, Illinois, United States

University of Illinois

Chicago, Illinois, United States

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, United States

Loyola University Medical Center

Maywood, Illinois, United States

Saint Jude Midwest Affiliate

Peoria, Illinois, United States

Riley Hospital for Children

Indianapolis, Indiana, United States

Blank Children's Hospital

Des Moines, Iowa, United States

University of Iowa/Holden Comprehensive Cancer Center

Iowa City, Iowa, United States

University of Kentucky/Markey Cancer Center

Lexington, Kentucky, United States

Norton Children's Hospital

Louisville, Kentucky, United States

Children's Hospital New Orleans

New Orleans, Louisiana, United States

Ochsner Medical Center Jefferson

New Orleans, Louisiana, United States

Maine Children's Cancer Program

Scarborough, Maine, United States

Sinai Hospital of Baltimore

Baltimore, Maryland, United States

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, United States

Walter Reed National Military Medical Center

Bethesda, Maryland, United States

Tufts Children's Hospital

Boston, Massachusetts, United States

C S Mott Children's Hospital

Ann Arbor, Michigan, United States

Bronson Battle Creek

Battle Creek, Michigan, United States

Corewell Health Dearborn Hospital

Dearborn, Michigan, United States

Children's Hospital of Michigan

Detroit, Michigan, United States

Michigan State University

East Lansing, Michigan, United States

Corewell Health Grand Rapids Hospitals - Butterworth Hospital

Grand Rapids, Michigan, United States

Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital

Grand Rapids, Michigan, United States

Trinity Health Grand Rapids Hospital

Grand Rapids, Michigan, United States

Bronson Methodist Hospital

Kalamazoo, Michigan, United States

West Michigan Cancer Center

Kalamazoo, Michigan, United States

Beacon Kalamazoo

Kalamazoo, Michigan, United States

Trinity Health Muskegon Hospital

Muskegon, Michigan, United States

Corewell Health Lakeland Hospitals - Niles Hospital

Niles, Michigan, United States

Cancer and Hematology Centers of Western Michigan - Norton Shores

Norton Shores, Michigan, United States

Corewell Health Reed City Hospital

Reed City, Michigan, United States

Corewell Health Children's

Royal Oak, Michigan, United States

Corewell Health William Beaumont University Hospital

Royal Oak, Michigan, United States

Corewell Health Lakeland Hospitals - Marie Yeager Cancer Center

Saint Joseph, Michigan, United States

Corewell Health Lakeland Hospitals - Saint Joseph Hospital

Saint Joseph, Michigan, United States

Munson Medical Center

Traverse City, Michigan, United States

Corewell Health Beaumont Troy Hospital

Troy, Michigan, United States

University of Michigan Health - West

Wyoming, Michigan, United States

Children's Hospitals and Clinics of Minnesota - Minneapolis

Minneapolis, Minnesota, United States

University of Minnesota/Masonic Cancer Center

Minneapolis, Minnesota, United States

University of Mississippi Medical Center

Jackson, Mississippi, United States

Children's Mercy Hospitals and Clinics

Kansas City, Missouri, United States

Cardinal Glennon Children's Medical Center

St Louis, Missouri, United States

Washington University School of Medicine

St Louis, Missouri, United States

Mercy Hospital Saint Louis

St Louis, Missouri, United States

Children's Hospital and Medical Center of Omaha

Omaha, Nebraska, United States

University of Nebraska Medical Center

Omaha, Nebraska, United States

Carson Tahoe Regional Medical Center

Carson City, Nevada, United States

Comprehensive Cancer Centers of Nevada - Henderson

Henderson, Nevada, United States

Comprehensive Cancer Centers of Nevada-Horizon Ridge

Henderson, Nevada, United States

Las Vegas Cancer Center-Henderson

Henderson, Nevada, United States

OptumCare Cancer Care at Seven Hills

Henderson, Nevada, United States

Comprehensive Cancer Centers of Nevada-Southeast Henderson

Henderson, Nevada, United States

OptumCare Cancer Care at Charleston