Combination Chemotherapy With or Without Blinatumomab in Treating Patients With Newly Diagnosed BCR-ABL-Negative B Lineage Acute Lymphoblastic Leukemia

Running, not enrolling · Phase 3

Conditions studied: Acute Lymphoblastic Leukemia, B Acute Lymphoblastic Leukemia, Philadelphia Chromosome Negative

In brief

This randomized phase III trial studies combination chemotherapy with blinatumomab to see how well it works compared to induction chemotherapy alone in treating patients with newly diagnosed breakpoint cluster region (BCR)-c-abl oncogene 1, non-receptor tyrosine kinase (ABL)-negative B lineage acute lymphoblastic leukemia. Drugs used in chemotherapy 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. Immunotherapy with monoclonal antibodies, such as blinatumomab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. It is not yet known whether combination chemotherapy is more effective with or without blinatumomab in treating newly diagnosed acute lymphoblastic leukemia.

Key facts

Study ID

NCT02003222

Run by

National Cancer Institute (NCI)

People needed

488

Starts

2014-05-19

Expected to finish

2027-02-25

Last updated by the study team

2026-08-04

Who can join

Age: 30 and older, up to 70. Sex: any. Healthy volunteers: accepted.

You may qualify if…

• PRE-REGISTRATION
• Diagnostic bone marrow and/or peripheral blood specimens must be submitted for immunophenotyping and selected molecular testing, and the establishment of BCR/ABL status; testing will be performed by the Eastern Cooperative Oncology Group (ECOG)-American College of Radiation Imaging Network (ACRIN) Leukemia Translational Research Laboratory (LTRL) and reported to the institution
• NOTE: IT IS ESSENTIAL THAT A SAMPLE CONTAINING SUFFICIENT BLAST CELLS BE SUBMITTED TO THE ECOG-ACRIN LTRL AT BASELINE SO THAT SUBSEQUENT BONE MARROW ASSESSMENTS OF MRD CAN BE DONE; IN ADDITION TO ALLOWING THE LTRL TO CONFIRM ELIGIBILITY BASED ON BLAST CELL IMMUNOPHENOTYPE AND BCR/ABL STATUS, IT IS ALSO IMPERATIVE THAT AN ADEQUATE NUMBER OF BLASTS BE BANKED FOR ANALYSIS BY DRS MULLIGHAN/WILLMAN. WITHOUT ADEQUATE BASELINE SAMPLES, PATIENTS WILL NOT BE ABLE TO BE TREATED AND RANDOMIZED ON THIS PROTOCOL; IF A BONE MARROW ASPIRATE IS NOT AVAILABLE FOR LTRL SUBMISSION AT BASELINE, IT IS IMPERATIVE THAT DR PAIETTA FROM THE LTRL IS CALLED TO DISCUSS THE PERIPHERAL BLOOD WHITE BLOOD CELL (WBC) AND BLAST COUNT BEFORE BLOOD ONLY IS SUBMITTED
• NOTE: Hydroxyurea can be given for up to 5 days prior to initiation of protocol therapy for control of leukocyte count and/or other symptoms or signs; corticosteroids can be given after pre-registration to the protocol and submission of baseline marrow and blood samples for control of leukocyte count and/or other symptoms or signs prior to initiation of protocol therapy if needed; if corticosteroids are given prior to pre-registration, contact the study chair as the patient may still be eligible to participate
• INDUCTION ELIGIBILITY CRITERIA-STEP 1
• Age >= 30 years and =< 70 years
• New diagnosis of B lineage ALL must be made upon bone marrow or peripheral blood immunophenotyping; cases with myeloid antigen expression, but unequivocal lymphoid immunophenotype, are eligible
• Negativity for the Philadelphia chromosome must be established by conventional cytogenetics, fluorescence in situ hybridization (FISH) and/or polymerase chain reaction (PCR); patients who are negative for the Philadelphia chromosome by conventional cytogenetics must have FISH or PCR performed for BCR/ABL to exclude occult translocations
• Cytogenetic analysis must be performed from diagnostic bone marrow (preferred) or if adequate number of circulating blasts from peripheral blood; FISH testing for common B-lineage ALL abnormalities including t(9;22) (BCR/ABL1), t(12;21) (ETS-variant gene 6 [ETV6]/runt-related transcription factor 1 [RUNX1]), t(1;19) (pre-B-cell leukemia homeobox 1 [PBX1]/transcription factor 3 [TCF3]), +4,+10,+17, (centromeric [Cen]4/Cen10/Cen17), t(11q23;var), (myeloid/lymphoid or mixed lineage leukemia [MLL]), deletion (del)(9p) (cyclin-dependent kinase inhibitor 2A [CDKN2A]/Cen9), and t(14;var) (immunoglobulin heavy chain [IGH] is encouraged); if there are few or no circulating blasts and an adequate marrow sample cannot be obtained for cytogenetic analysis, the patient may still enroll on the trial
• Serum direct bilirubin < 2 mg/dl or serum total bilirubin =< 3 (obtained =< 48 hours prior to registration); NOTE: the above stipulation for normal hepatic function does not apply if liver dysfunction is due to leukemia infiltration
• Serum creatinine < 2 mg/dl (obtained =< 48 hours prior to registration); NOTE: the above stipulation for normal hepatic function does not apply if liver dysfunction is due to leukemia infiltration
• Patient should be human leukocyte antigen (HLA) typed (A, B, C, DR and DQ) during induction therapy phase or a written explanation for not undergoing HLA typing on the flow sheet
• Patients with known human immunodeficiency virus (HIV) infection are eligible if they meet all of the following criteria:
• No history of acquired immune deficiency syndrome (AIDS)-related complications other than a history of low CD4+ T-cell count (< 200/mm\^3) prior to initiation of combination antiretroviral therapy; on study CD4+ T-cell count may not be informative due to leukemia and should not be used as an exclusion criterion if low
• Patient must be healthy on the basis of HIV disease with high likelihood of near normal life span were it not for the leukemia
• Patient must have serum HIV viral load of < 200 copies/mm\^3
• Patient must be on combination antiretroviral therapy with minimal pharmacokinetic interactions with study therapy and minimal overlapping clinical toxicity with protocol therapy
• Patient must not be receiving protease inhibitors or once daily formulations containing cobicistat, stavudine, or on regimens containing stavudine or zidovudine
• It is recommended to utilize a regimen of the integrase inhibitor, dolutegravir, combined with either disoproxil fumarate/emtricitabine or dolutegravir combined with tenofovir alafenamide/emtricitabine
• Patient must have no history of recent myocardial infarction (within three months), uncontrolled congestive heart failure, or uncontrolled cardiac arrhythmia
• Patient must have a normal cardiac ejection fraction by pretreatment multigated acquisition scan (MUGA) or echocardiogram within 4 weeks prior to registration (resting ejection fraction >= 40% or >= 5% increase with exercise), shortening fraction by echocardiogram >= 24%, or to within the normal range of values for the institution
• Women must not be pregnant or breast-feeding due to administration of teratogenic chemotherapy and must not become pregnant or breastfeed during protocol therapy and for at least 3 months after protocol therapy; woman of childbearing potential must abstain from sexual activity or be willing to use 2 highly effective forms of contraception throughout protocol therapy and for at least an additional 3 months after the last dose of protocol-specified therapy; all females of childbearing potential must have a blood test or urine study within 2 weeks prior to registration to rule out pregnancy; a female of childbearing potential is any woman, regardless of whether they have undergone tubal ligation, who meets the following criteria: has not undergone a hysterectomy or bilateral oophorectomy; or has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
• Men who have a female partner of childbearing potential must be willing to use 2 highly effective forms of contraception throughout protocol therapy and for at least an additional 3 months after the last dose of protocol-specified therapy; men who have a pregnant partner must be willing to use a condom during sexual activity throughout protocol therapy and for 3 months after the last dose of protocol-specified therapy
• ECOG performance score 0-3
• Patient must have given written informed consent

You may not qualify if…

• Mature B ALL (Burkitt's-like leukemia) is excluded from enrollment in this trial; pre-study bone marrow biopsy and aspirate must be completed =< 1 week prior to registration
• Patient must not have a concurrent active malignancy for which they are receiving treatment
• Patient must not have intercurrent organ damage or medical problems that will jeopardize the outcome of therapy (i.e., psychiatric disorder, drug abuse, pregnancy)
• Patient must not have an antecedent hematologic disorder
• Patient must not have a history or presence of clinically relevant central nervous system (CNS) pathology such as epilepsy, seizure, paresis, aphasia, stroke, severe brain injuries, dementia; Parkinson's disease, cerebellar disease, organic brain syndrome, psychosis, or other significant CNS abnormalities
• Patient must not have an active uncontrolled infection

Where it is running

• 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 Regional Hospital — 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
• Kingman Regional Medical Center — Kingman, Arizona, United States
• Banner University Medical Center - Tucson — Tucson, Arizona, United States
• University of Arizona Cancer Center-North Campus — Tucson, Arizona, United States
• Mercy Hospital Fort Smith — Fort Smith, Arkansas, United States
• University of Arkansas for Medical Sciences — Little Rock, Arkansas, United States
• PCR Oncology — 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
• UC San Diego Moores Cancer Center — La Jolla, California, United States
• UC Irvine Health/Chao Family Comprehensive Cancer Center — Orange, California, United States
• Stanford Cancer Institute Palo Alto — Palo Alto, California, United States
• Rocky Mountain Cancer Centers-Aurora — Aurora, Colorado, United States
• The Medical Center of Aurora — Aurora, Colorado, United States
• University of Alabama at Birmingham Cancer Center — Birmingham, Alabama, United States

Full record on ClinicalTrials.gov

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