A Phase II Study of Blinatumomab (NSC-765986) and POMP (Prednisone, Vincristine, Methotrexate, 6-Mercaptopurine) for Patients >/= 65 Years of Age with Newly Diagnosed Philadelphia Chromosome Negative (Ph-) Acute Lymphocytic Leukemia (ALL) and of Dasatinib (NSC-732517), Prednisone and Blinatumomab for Patients >/= 65 Years of Age with Newly Diagnosed Philadelphia-Chromosome Positive (Ph+) ALL, and Philadelphia-Chromosome-Like Signature (Ph-Like) ALL (Newly Diagnosed or Relapsed/Refractory) with Known or Presumed Activating Dastainib-Sensitive Mutations or Kinase Fusions (DSMKF)
Cohort 1 is permanently closed effective 9/15/17.
Investigators must complete the Blinatumomab Outpatient Administration Training Verification, accessible from the "Required S1318 Training Material" link on the SWOG S1318 protocol abstract page (below). This verification is required in order for sites to register patients to this study. This requirement generally takes 2-3 days to process through CTSU.
Other Study Materials
Eligibility Criteria Expand/Collapse
Pts must have a new morphologic dx of precursor B cell acute lymphoblastic leukemia (ALL) (non T cell); Pts with Burkitts (L3) are excluded. Pts w/Ph+ or Ph-Like ALL w/dasatinib-sensitive mutations or kinase fusions may have relapsed/refractory diagnoses; Pts must have a dx of Philadelphia chromosome negative ALL or Ph chromosome positive ALL by cytogenetics, FISH, or PCR; Newly diagnosed pts must have evidence of ALL in their marrow or peripheral blood with at least 20% lymphoblasts present in blood or bone marrow; Relapsed/refractory pts must have >/= 5% lymphoblasts in blood or bone marrow; Pts with only extramedullary disease in the absence of bone marrow or blood involvement are not eligible; If aspirate is dry tap, IHC testing (incl CD19) must be performed on bone marrow biopsy to determine lineage; Patient must not have a history or presence of clinically relevant CNS pathology such as epilepsy, seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinsonï¿½s disease, cerebellar disease, organic brain syndrome, psychosis, active ALL in the CNS confirmed by CSF analysis, or other significant CNS abnormalities; Pts must have a lumbar puncture to determine CNS involvement of ALL; Pts must not have received any prior chemo, RT, or other therapy for the txt of ALL (other than those noted below) and must not be receiving any immunosuppressive therapy. Pts may not have received any prior investigational therapy w/in 28 days prior to reg. Pts may have received the following w/in any time prior to reg: low dose chemo, TKI therapy, steroids, hydroxyurea, leukapheresis, intrathecal chemo or vincristine. Pts must not have received any monoclonal antibody therapy w/in 42 days of reg; Pts must be â‰¥ 65 years of age. For pts 65-69 years of age, pt must be deemed not suitable for standard intensive Induction chemo at the discretion of the local investigator, or must have refused standard intensive chemo; Pts must not be candidates for allogeneic hematopoietic stem cell transplant; Pts must have complete history and physical examination w/in 28 days; Pts must have a Zubrod Performance Status of 0-2; W/in 14 days prior to reg: a) Pts must have serum creatinine â‰¤ 1.5 mg/d, (b) Pts must have AST and ALT â‰¤ 3.0 x Institutional Upper Limit of Normal(IULN), (c) Pts must have alkaline phosphatase â‰¤ 2.5 x IULN, (d) Pts must not have CTCAE â‰¥ Gr 2 neuropathy (cranial, motor or sensory; Pts must not have systemic fungal, bacterial, viral or other infection that is not controlled (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other txt); Pts known to be positive for HIV (the human immunodeficiency virus) may be eligible, providing they meet the following additional criteria w/in 28 days prior to reg: ï¿½ No history of AIDS-defining conditions ï¿½ CD4 cells > 350 cells/mm3 ï¿½ If on antiretroviral agents, must not include zidovudine or stavudine ï¿½ Viral load â‰¤ 50 copies HIV mRNA/mm3 if on cART or â‰¤ 25,000 copies HIV mRNA/mm3 if not on cART. ï¿½ HAART regimens are acceptable providing they have only weak P450A4 interactions; Pts must not have any known autoimmune disease; Pts must not have testicular involvement. If clinical or ultrasound findings are equivocal, biopsy must be performed. All tests for establishing testicular involvement must be completed w/in 14 days prior to reg; Pts with evidence of extramedullary disease at dx will have CT scan or MRI of the chest, abdomen and pelvis to obtain baseline values w/in 28 days prior to reg; No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated Stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for five years.
Cohort1 Ph- Pts Only:
Pts must have the following tests w/in 28 days prior to reg to obtain baseline measurements: ï¿½ PT/PTT/INR/fibrinogen ï¿½ Neurologic assessment
Cohort 2 Ph+ Pts Only:
Pts must not have active pericardial effusion, ascites or pleural effusion of any Gr based on chest x-ray and echocardiogram w/in 28 days prior to reg. Exception: If the effusion is suspected to be related to the leukemia, the patient may have pericardial effusion â‰¤ Gr 2 or pleural effusion
â‰¤ GR 1; Pts must have ejection fraction â‰¥ 45% based on echocardiogram performed w/in 28 days prior to reg; Pts must have QTcF (by Fridericia calculation) < 480/msec based on EKG
performed w/in 28 days prior to reg. QTcF = QT/(RR)0.33 (QTcF = QT interval divided by the cube root of the RR [heart rate] in seconds); Pts must not be receiving any proton pump inhibitors at the time of reg.
Pretreatment cytogenetics must be performed on all pts. Collection of pretreatment specimens must be completed w/in 28 days prior to reg; If a patient is Ph-positive, PCR for both p190 and p210 must be sent; Cohort 1 (Ph-negative): Pts must have specimens submitted for blinatumomab immunogenicity assessment. Collection of pretreatment specimens must be completed w/in 28 days prior to reg to S1318; Cohort 2 (Ph-positive): Pts must agree to have specimens submitted for blinatumomab immunogenicity testing if subsequently moved to a blinatumomab containing txt regimen on protocol.
Publication Information Expand/Collapse
Results of SWOG 1318: A Phase 2 Trial of Blinatumomab Followed By Pomp (Prednisone, Vincristine, Methotrexate, 6-Mercaptopurine) Maintenance in Elderly Patients with Newly Diagnosed Philadelphia Chromosome Negative B-Cell Acute Lymphoblastic Leukemia