AALL1331

Principal Investigator: Phillip Barnette
Keywords: Pediatric , Oncology , Relapsed Leukemia , Relapsed B-cell ALL Department: Pediatric Administration
IRB Number: 00079750 Co Investigator:  
Specialty: Oncology
Sub Specialties:
Recruitment Status: Recruiting

Contact Information

Jennifer Craig
jennifer.craig@imail.org
8016624715

Brief Summary

Primary Aims

1. 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).


2. 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

3. 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).


4. 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

5. 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.

6. 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.

7. 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)

8. To evaluate blinatumomab pharmacokinetics (PK) and explore exposure-response relationships for measures of safety and effectiveness.

Inclusion Criteria

DIAGNOSTIC REQUIREMENTS:

Patients must be equal to or greater than 1 year of age and less than 31 years of age.

Patients must be diagnosed with first relapse of B-ALL with or without extramedullary disease. Clarified with Amendment 2: Extramedullary sites are limited to the CNS and testicles.

There is 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.

For 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, or Maintenance chemotherapy. Added with Amendment 2: or intrathecal chemotherapy administered at the time of the required diagnostic lumbar puncture to establish baseline CNS status.

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 has not had a prior stem cell transplant or rescue.

Patient has not had prior treatment with blinatumomab.

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.

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:

Age

Maximum Serum

Creatinine (mg/dL)

Male

Female

1 to < 2 years

0.6

0.6

2 to < 6 years

0.8

0.8

6 to < 10 years

1

1

10 to < 13 years

1.2

1.2

13 to < 16 years

1.5

1.4

≥ 16 years

1.7

1.4

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.

REGULATORY REQUIREMENTS:

All patients and/or their parents or legal gaurdians must sign a written informed consent.

All institutional, FDA and NCI requirements for human studies must be met.

 

 

Exclusion Criteria

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 eligible

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 involvement.

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 potential.

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.)