Risk-Stratified Randomized Phase III Testing of Blinatumomab (IND# 117467, NSC#765986) in First Relapse of Childhood B-Lymphoblastic Leukemia (B-ALL)
Clinical Trial Information
Trial Contact: El-Shami, Jessica
Trial Phone: 321.841.3837
IRB No: AALL1331
Principal Investigator: Vincent F. Giusti, MD
Sub Investigators: AguilarBonilla, Ana MD; Eslin, Don MD; Kelly, Susan MD; Levy, Alejandro MD; Pope, Michele ARNP; Smith, Amy MD; Story, Allison ARNP; Sullivan, Kelly ARNP; Sutphin, Robert MD; Wieber, Laura ARNP
Phase: Drug: Phase III
Age Group: Pediatric
Secondary Protocol No: AALL1331
Applicable Disease Sites: First Relapse B-ALL
Therapies Involved: Intrathecal Medication; Chemotherapy ; Radiaition
ClinicalTrials.gov ID: NCT02101853
Primary Aims To compare disease free survival (DFS) of HR and IR relapse B-ALL patients who are randomized following Induction Block 1 chemotherapy to receive either two intensive chemotherapy blocks or two 5-week blocks of blinatumomab (HR/IR Randomization). To compare DFS of LR relapse B-ALL patients who are randomized following Block 1 chemotherapy to receive either chemotherapy alone or chemotherapy plus blinatumomab (LR Randomization). Secondary Aims To compare overall survival (OS) of HR and IR relapse B-ALL patients who are randomized following Induction Block 1 chemotherapy to receive either two intensive chemotherapy blocks or two 5 week blocks of blinatumomab (HR/IR Randomization). To compare OS of LR relapse B-ALL patients who are randomized following Block 1 chemotherapy to receive either chemotherapy alone or chemotherapy plus blinatumomab (LR Randomization Exploratory Aims To compare the rates of MRD ≥ 0.01% at the end of Block 2 and Block 3 for HR and IR relapse B-ALL patients in HR/IR randomization. To estimate, for treatment failure (TF) patients not previously receiving blinatumomab, the hematologic complete remission rate (CR), rate of MRD < 0.01%, and proportion able to proceed to hematopoietic stem cell transplant (HSCT) in CR after treatment with blinatumomab. To assess the feasibility and safety of rapid taper of immune suppression for the subset of HSCT patients with MRD ≥ 0.01% pre- and/or post-HSCT with no acute graft versus host disease (aGVHD). To evaluate blinatumomab pharmacokinetics (PK) and explore exposure-response relationships for measures of safety and effectiveness.
Patients ≥1 year and < 31 years of age at the time of relapse will be eligible.
First relapse of B-ALL, allowable sites of disease include
isolated bone marrow, combined bone marrow and CNS
and/or testicular, and isolated CNS and/or testicular.
Extramedullary sites are limited to the CNS and testicles.
Please refer to Section 3.3 for definitions of relapse and
criteria for risk classification.
Review- concomitant therapy restrictions for patients during
No waiting period for patients who relapse while receiving
standard Maintenance therapy
Patients who relapse on frontline therapy in phases other than
Maintenance must have fully recovered from the acute toxic
effects of all prior chemotherapy, immunotherapy, or
radiotherapy prior to entering this study.
Cytotoxic therapy: At least 14 days since the completion of
cytotoxic therapy with the exception of hydroxyurea, which is
permitted up to 24 hours prior to the start of protocol therapy, .
Biologic (anti-neoplastic) agent: At least 7 days since the
completion of therapy with a biologic agent. For agents that
have known adverse events occurring beyond 7 days after
administration, this period must be extended beyond the time
during which adverse events are known to occur.
Stem cell transplant or rescue: Patient 18.104.22.168 Stem cell
transplant or rescue: Patient has not had a prior stem cell
transplant or rescue.
Patient has not had prior treatment with blinatumomab.
With the exception of intrathecal chemotherapy (methotrexate
strongly preferred) administered at the time of the required
diagnostic lumbar puncture to establish baseline CNS status,
patient has not received prior relapse-directed therapy (i.e.,
this protocol is intended as the INITIAL treatment of first
Patients must have a performance status corresponding to
ECOG scores of 0, 1, or 2. Use Karnofsky for patients > 16
years of age and Lansky for patients ≤ 16 years of age.
Organ Function Requirements
Adequate Renal Function Defined As:
- Creatinine clearance or radioisotope GFR ≥ 70 mL/min/1.73 m2 or
- A serum creatinine based on age/gender as follows:
Maximum Serum Creatinine (mg/dL)
1 to < 2 years
2 to < 6 years
6 to < 10 years
10 to < 13 years
13 to < 16 years
≥ 16 years
Adequate liver function defined as a direct bilirubin < 3.0 mg/dL.
Adequate Cardiac Function Defined As:
Shortening fraction of ≥ 27% by echocardiogram, or
Ejection fraction of ≥ 50% by radionuclide angiogram.
Patients with Philadelphia chromosome positive/BCR-ABL1+
ALL are not eligible
Patients with Burkitt Leukemia/Lymphoma or mature B-cell
leukemia are not eligible
Patients with T-Lymphoblastic Leukemia (T-
ALL)/Lymphoblastic Lymphoma (T- LL) are not eligible
Patients with B-Lymphoblastic Lymphoma (B-LL) are not
Patients with known optic nerve and/or retinal involvement
are not eligible. Patients who are presenting with visual
disturbances should have an ophthalmologic exam and, if
indicated, an MRI to determine optic nerve or retinal
Patients known to have one of the following concomitant
genetic syndromes: Down syndrome, Bloom syndrome,
ataxia-telangiectasia, Fanconi anemia, Kostmann
syndrome, Shwachman syndrome or any other known
bone marrow failure syndrome.
Patients with known HIV infection.
Patients with known allergy to mitoxantrone, cytarabine, or
both etoposide and etoposide phosphate (Etopophos).
Lactating females who plan to breastfeed.
Patients who are pregnant since fetal toxicities and teratogenic
effects have been noted for several of the study drugs. A
pregnancy test is required for female patients of childbearing
Sexually active patients of reproductive potential who have not
agreed to use an effective contraceptive method for the
duration of their study participation.
Patients with pre-existing significant central nervous system
pathology that would preclude treatment with blinatumomab,
including: history of severe brain injury, dementia, cerebellar
disease, organic brain syndrome, psychosis,
coordination /movement disorder, or autoimmune disease
with CNS involvement are not 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 uncontrolled seizure disorder are not eligible.
(Patients with seizure disorders that do not require
antiepileptic drugs, or are well controlled with stable doses
of antiepileptic drugs remain eligible.)