Blinatumomab and Nivolumab With or Without Ipilimumab in Treating Patients With Poor-Risk Relapsed or Refractory CD19+ Precursor B-Lymphoblastic Leukemia

NCT02879695 | Active Not Recruiting Phase 1 Results FDA Drug

• 4 other identifiers: NCI-2016-01300ETCTN1003010030UM1CA186691
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 7

Brief Summary

This phase I trial studies the side effects and best dose of blinatumomab when given with nivolumab alone or nivolumab and ipilimumab in treating patients with poor-risk CD19+ precursor B-lymphoblastic leukemia that has come back after a period of improvement (relapsed) or has not responded to treatment (refractory). Immunotherapy with monoclonal antibodies, such as blinatumomab, nivolumab, and ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

Conditions

Refractory Mixed Phenotype Acute Leukemia; Refractory B Acute Lymphoblastic Leukemia; Recurrent B Acute Lymphoblastic Leukemia; Recurrent Mixed Phenotype Acute Leukemia

Outcome Measures

Primary Outcomes (2)

• Number of Participants Experiencing Grade 3, 4, or 5 Adverse Events

  Defined by Common Terminology Criteria for Adverse Events, version 5.0. The highest grade experienced by the participant will be reported.

  Up to 5.5 years

• Number of Participants With Dose Limiting Toxicities

  Maximum tolerated dose was determined by the absence of dose limiting toxicity in each patient assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Dose Limiting Toxicities were evaluated during treatment; therefore, the time frame is from the first participant starting treatment to the last participant completing treatment.

  Up to 5.5 years

Secondary Outcomes (4)

• Count of Participants Responders With Minimal Residual Disease

  Up to 5.5 years

• Number of Participants Achieving Remission

  Up to 5.5 years

• Duration of Response

  Up to 5.5 years

• Overall Survival

  Up to 5.5 years

Other Outcomes (6)

• Changes in Absolute Lymphocyte Count

  About 1 year

• Changes in Distribution of T Cell Subsets and Differentiation Status, Natural Killer (NK) Cells, and B Cells

  About 1 year

• Changes in T Cell Co-signaling Receptors Expression

  About 1 year

Study Arms (1)

Treatment (blinatumomab, nivolumab, ipilimumab)

EXPERIMENTAL

Patients receive blinatumomab IV continuously on days 1-28. Treatment repeats every 42 days for up to 5 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive nivolumab IV over 30 minutes on day 11 and then every 2 weeks for up to year. Some patients also receive ipilimumab IV over 90 minutes on day 11 and then every 6 weeks for up to 1 year. Patients also undergo bone marrow aspiration and biopsy and blood sample collection throughout the study.

Procedure: Biospecimen Collection; Biological: Blinatumomab; Procedure: Bone Marrow Aspiration and Biopsy; Biological: Ipilimumab; Biological: Nivolumab

Interventions

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (blinatumomab, nivolumab, ipilimumab)

Blinatumomab BIOLOGICAL

Given IV

Also known as: AMG 103, AMG-103, AMG103, Anti-CD19 x Anti-CD3 Bispecific Monoclonal Antibody, Anti-CD19/Anti-CD3 Recombinant Bispecific Monoclonal Antibody MT103, Blincyto, MEDI 538, MEDI-538, MEDI538, MT 103, MT-103, MT103

Treatment (blinatumomab, nivolumab, ipilimumab)

Bone Marrow Aspiration and Biopsy PROCEDURE

Undergo bone marrow aspiration and biopsy

Treatment (blinatumomab, nivolumab, ipilimumab)

Ipilimumab BIOLOGICAL

Given IV

Also known as: Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody, BMS 734016, BMS-734016, BMS734016, Ipilimumab Biosimilar CS1002, MDX 010, MDX-010, MDX-CTLA4, MDX010, Yervoy

Treatment (blinatumomab, nivolumab, ipilimumab)

Nivolumab BIOLOGICAL

Given IV

Also known as: ABP 206, BCD-263, BMS 936558, BMS-936558, BMS936558, CMAB819, MDX 1106, MDX-1106, MDX1106, NIVO, Nivolumab Biosimilar ABP 206, Nivolumab Biosimilar BCD-263, Nivolumab Biosimilar CMAB819, ONO 4538, ONO-4538, ONO4538, Opdivo

Treatment (blinatumomab, nivolumab, ipilimumab)

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• PRE-REGISTRATION ELIGIBILITY CRITERIA
• Patients must have suspected refractory or relapsed pre-B cell ALL or mixed phenotype acute leukemia (MPAL), or if newly diagnosed, the patient must be 60 years of age or older
• Bone marrow and/or peripheral blood specimens will be submitted for correlative studies; patients who have a dry tap will still be eligible
• REGISTRATION ELIGIBILITY CRITERIA
• Patients must have histologically or cytologically confirmed by the local institution CD19+ precursor B-acute lymphoblastic leukemia (pre-B cell ALL) OR CD19+ mixed phenotype acute leukemia (MPAL): a) with relapse following or refractory to at least one prior line of therapy if older than 21 years; b) in second or higher relapse or refractory to at least two prior lines of therapy if 21 years old and younger (16-21); c) or they must have a new diagnosis of pre-B cell ALL or CD19+ MPAL but are \>= 60 years old and are either not a candidate for or do not wish to receive traditional induction chemotherapy
• The evidence of CD19+ expression on leukemia cells must be confirmed by pathology review of the bone marrow and/or peripheral blood specimens (flow cytometry and/or immunohistochemistry) collected at the time of current relapse and prior to the initiation of therapy
• Patients with Philadelphia chromosome (Ph) positive (+) pre-B cell ALL OR Ph+ MPAL will be eligible if they have been refractory to or intolerant of treatment with at least 1 second-generation or third-generation tyrosine kinase inhibitor (TKI)
• Patients who were treated with blinatumomab in the past will be allowed on the study as long as they have persistent CD19 expression on leukemia cells and did not experience unacceptable toxicities with prior blinatumomab administration; patients who were treated with chimeric antigen receptor (CAR)-modified T cells targeting CD19 in the past will be allowed on the study as long as they have persistent CD19 expression on leukemia cells
• Patients with a history of allogeneic hematopoietic stem cell transplantation (HSCT) will be eligible if they are more than 90 days removed from the date of stem cell infusion, have no evidence of acute graft-versus-host disease (GVHD) or active chronic (grade 2-4) GVHD, and are off of all transplant-related immunosuppression for at least 2 weeks
• Age \>= 16 years. Because no dosing or adverse event data are currently available on the use of blinatumomab in combination with nivolumab ± ipilimumab in pediatric patients, children are excluded from this study, but will be eligible for future pediatric trials.
• Eastern Cooperative Oncology Group (ECOG)/Karnofsky performance status of 0-2 (Karnofsky \>= 60%)
• Life expectancy of greater than 12 weeks
• Total bilirubin =\< 2.0 mg/dL (except patients with Gilbert syndrome, who can have total bilirubin \< 3.0 mg/dL)
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 5 x upper limit of normal (ULN)
• Serum creatinine =\< 1.5 x ULN OR creatinine clearance (CrCl) \>= 50 mL/min (if using the Cockcroft-Gault formula)

You may not qualify if:

• Patients who have had chemotherapy or other systemic therapy or radiotherapy, or those who have not recovered from adverse events due to prior administered agents as follows: chemotherapy, radiotherapy or surgery =\< 3 weeks prior to entering the study, targeted therapy (e.g., TKI) =\< 1 week prior to entering the study; autologous HSCT =\< 6 weeks prior to entering the study; investigational drug or immunotherapy (e.g. rituximab) =\< 4 weeks prior to entering the study; prophylactic intrathecal chemotherapy within one week of enrollment allowed; patients will be allowed to receive cytoreduction with hydroxyurea, 6-mercaptopurine, corticosteroids (dexamethasone, prednisone or similar) or cyclophosphamide provided that it is discontinued at least 24 hours prior to the initiation of study treatment; pre-phase treatment with dexamethasone 10 mg/m\^2 (maximum total 24 mg per day) for up to 5 days is required for patients with bone marrow blasts more than 50%, peripheral blood blasts of 15,000/uL or higher, or elevated lactate dehydrogenase suggesting rapidly progressing disease as per investigator's assessment; pre-phase treatment must be stopped at least 24 hours prior to the initiation of blinatumomab
• Patients who are receiving any other investigational agents
• Patients should be excluded if they have had prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways
• Patients with active central nervous system leukemia are excluded from this clinical trial because they may develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events; patients with a history of central nervous system (CNS) leukemia but no active disease at the time of enrollment are eligible; the absence of CNS disease must be confirmed by flow cytometric and cytologic examination of the cerebrospinal fluid (CSF) within 7 days of study enrollment
• Active leukemia in the testes or isolated extramedullary relapse; patients with a history of treated leukemia in testes but no active disease at the time of enrollment are eligible
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to nivolumab, ipilimumab, or blinatumomab
• History of severe hypersensitivity reaction to any monoclonal antibody
• Uncontrolled intercurrent illness including, but not limited to, active, uncontrolled infection; symptomatic congestive heart failure; unstable angina pectoris; cardiac arrhythmia; or psychiatric illness/social situations that would limit compliance with study requirements; patients with infection under treatment and controlled with antibiotics are eligible
• Pregnant women are excluded from this study because nivolumab and ipilimumab have the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with nivolumab and ipilimumab, breastfeeding should be discontinued if the mother is treated with nivolumab and ipilimumab; these potential risks may also apply to blinatumomab
• History of any chronic hepatitis including alcoholic, non-alcoholic steatohepatitis (NASH), drug related, autoimmune, chronic viral positive tests for hepatitis B virus surface antigen (HBsAg), hepatitis B core antibody (anti-HBc) in the absence of hepatitis B surface antibody (anti-HBs), or a positive hepatitis C (HCV) viral load; these patients are excluded due to the risk for autoimmune hepatitis with immune checkpoint inhibitors exacerbating their known liver disease as well as the unknown risk for hepatitis B and/or C reactivation with blinatumomab and immune checkpoint inhibitors
• Subjects with active autoimmune disease, a history of known or suspected autoimmune disease or a history of a syndrome requiring systemic corticosteroids (\> 10 mg daily of prednisone equivalent) except for the treatment of malignancy with the exception of:
• Isolated vitiligo
• Resolved childhood atopy
• History of a positive antinuclear antibody (ANA) titer without associated symptoms or history of symptoms of an autoimmune disorder
• Controlled thyroid disorders

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (7)

Yale University

New Haven, Connecticut, 06520, United States

Location

University of Kentucky/Markey Cancer Center

Lexington, Kentucky, 40536, United States

Location

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, 21287, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

University of Pittsburgh Cancer Institute (UPCI)

Pittsburgh, Pennsylvania, 15232, United States

Location

Huntsman Cancer Institute/University of Utah

Salt Lake City, Utah, 84112, United States

Location

Related Publications (1)

• Shi Z, Zhu Y, Zhang J, Chen B. Monoclonal antibodies: new chance in the management of B-cell acute lymphoblastic leukemia. Hematology. 2022 Dec;27(1):642-652. doi: 10.1080/16078454.2022.2074704.

  PMID: 35622074 DERIVED

MeSH Terms

Conditions

Burkitt Lymphoma; Leukemia, Biphenotypic, Acute

Interventions

Specimen Handling; blinatumomab; N,N-dicyclohexyl-isoborneol-10-sulfonamide; Biopsy; Ipilimumab; CTLA-4 Antigen; Nivolumab

Condition Hierarchy (Ancestors)

Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Lymphoid; Leukemia; Hematologic Diseases

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Cytodiagnosis; Cytological Techniques; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Immune Checkpoint Proteins; Costimulatory and Inhibitory T-Cell Receptors; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins; Antigens, Differentiation, T-Lymphocyte; Antigens, Differentiation; Antigens, Surface; Antigens; Biological Factors; Biomarkers

Results Point of Contact

• Title: Grants Administrative Manager
• Organization: Johns Hopkins University/SKCCC

jmurra33@jhmi.edu

4439273568

Study Officials

• Ivana Gojo

  JHU Sidney Kimmel Comprehensive Cancer Center LAO

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 23, 2016
• First Posted: August 26, 2016
• Study Start: October 25, 2017
• Primary Completion: May 22, 2023
• Study Completion (Estimated): July 18, 2026
• Last Updated: April 29, 2026
• Results First Posted: October 16, 2024

Record last verified: 2026-01

Locations

US (7)