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Blinatumomab in Treating Patients with Pre B-Cell Acute Lymphoblastic Leukemia (ALL) and B-Cell Non-Hodgkin Lymphoma (NHL) Undergoing Stem Cell Transplant

Trial Status: Active

This phase Ib / II trial studies the side effects and how well blinatumomab works in treating patients with pre B-cell acute lymphoblastic leukemia and B-cell non-Hodgkin lymphoma (NHL) who undergo stem cell transplant. Blinatumomab is an antibody. Antibodies are made of proteins that the immune system uses to fight off foreign proteins such as the ones found in infectious organisms. Researchers have designed blinatumomab to engage body’s immune system to attack cells expressing CD19, a protein, which is commonly expressed on leukemia and lymphoma cells in patients with pre-B ALL or NHL. Immunotherapy with monoclonal antibodies, such as blinatumomab, may induce changes in the body's immune system and may interfere with the ability of cancer cells to grow and spread.

Inclusion Criteria

  • Pre-B ALL, low and high grade NHL who underwent an allogeneic (allo)HSCT using post transplant cyclophosphamide (CY) graft versus host disease (GVHD) prophylaxis (post transplant [Pt]-Cy alone or combination with MMF/tacrolimus or sirolimus) as follows: * Pre-B ALL patients in complete first remission (CR1) with high-risk features such as adverse cytogenetics including t(9;22) or Philadelphia (Ph)-like ALL, t(4;11) or other MLL (KMT2A) rearrangements, t(v;14q23)/IgH, complex karyotype (>= 5 chromosomal abnormalities), hypodiploidy (< 44 chromosomes), low hypodiploidy (30-39 chromosomes)/near triploidy (60-68 chromosomes), intrachromosomal amplification of chromosome 21 (iAMP21), high white blood count (WBC) count at presentation (>= 30,000), lack of achievement of complete remission after standard induction chemotherapy (but achieved CR1 following salvage or consolidation), or persistence of detectable disease after induction and consolidation (intensification) or pre-transplant as documented on any of routine clinical tests (morphology, flow cytometry, cytogenetics or molecular studies) OR all pre-B ALL patients in second and higher complete remission (CR). * Low and high grade NHL following a nonmyeloablative (reduced-intensity conditioning) transplant irrespective of pre-transplant disease status.
  • Patients should be at least 60 but not more than 180 days from transplant with documented count recovery (absolute neutrophil count [ANC] > 1 x 10^9/L, and non-transfused platelets > 30 x 10^9/L) and no evidence of disease progression.
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
  • Ability to give informed consent.
  • In agreement to use an effective barrier method of birth control (hormonal or barrier method of birth control; abstinence) to avoid pregnancy during the study and for a minimum of 30 days after study treatment, for all male and female patients who are fertile.
  • Patients may have received any number of prior regimens to achieve remission. Patients previously treated with blinatumomab will be eligible as long as they did not experience unacceptable toxicities with prior blinatumomab administration. If patient was refractory (no response) to blinatumomab in the past, patient will be eligible if there was no evidence of CD19 loss on leukemia cells.

Exclusion Criteria

  • Lack of engraftment (less than 85% donor deoxyribonucleic acid [DNA] in bone marrow or peripheral blood after allogeneic HSCT).
  • Active or untreated disease in central nervous system or testes.
  • Patient has received chemotherapy or radiotherapy (with the exception of intrathecal chemotherapy) within 2 weeks of starting blinatumomab. Patient could receive intrathecal prophylactic chemotherapy up to 24 hours prior to starting blinatumomab.
  • Patients with active uncontrolled infection or uncontrolled intercurrent illness including, but not limited to symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Patients with prior history of severe (grade 3 or 4) acute GVHD or active severe chronic GVHD even if resolved will not be eligible. Patients with history of active acute GVHD (grade 2) and active moderate chronic GVHD who required steroids for the treatment of GVHD will need to be off steroids for at least 4 weeks prior to treatment start. (Topical steroids or physiologic adrenal replacement steroid doses are allowed).
  • Patients requiring calcineurin inhibitors (i.e. tacrolimus or sirolimus) or other systemic immunosuppressants (cyclosporine (CNI); methotrexate or similar) for GVHD prophylaxis or treatment within 4 weeks prior to treatment start.
  • Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase > 5 X upper limit of normal (ULN).
  • Bilirubin >= 1.5 X ULN.
  • Creatinine >= 2 mg/dL.
  • Patients with Ph-positive ALL who are eligible for post-transplant tyrosine kinase inhibitor (TKI) maintenance based on a demonstrated sensitivity to TKIs pre-transplant (patients with known intolerance or resistance to TKI will be eligible).
  • Evidence of progressive disease post-transplant.
  • Women who are pregnant or lactating.
  • Known hypersensitivity to blinatumomab.
  • Patients with a concurrent active malignancy for which they are receiving treatment.
  • Concurrent use of any other investigational drugs.
  • Patient who 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, psychosis, or other significant CNS abnormalities. A history of treated CNS leukemia or lymphoma will be allowed if recent imaging and cerebrospinal fluid (CSF) studies confirm the absence of active CNS disease at the time of study entry.
  • Weight < 45 kg.
  • Patients receiving other post-transplant maintenance therapies.
  • Infection with human immunodeficiency virus (HIV) or chronic infection with hepatitis B virus or hepatitis C virus (HCV).

Georgia

Atlanta
Northside Hospital
Status: APPROVED
Contact: Scott R. Solomon
Phone: 404-255-1930

Maryland

Baltimore
Johns Hopkins University / Sidney Kimmel Cancer Center
Status: ACTIVE
Contact: Jonathan Allen Webster
Phone: 410-614-9106

PRIMARY OBJECTIVES:

I. Determine the safety and toxicity of incorporating blinatumomab into the post-allogeneic hematopoietic stem cell transplant (HSCT) maintenance setting for patients with CD19+-B-cell malignancies (acute lymphoblastic leukemia [ALL], non-Hodgkin’s lymphoma [NHL]). (Phase IB)

II. Determine if incorporating blinatumomab into the post-allogeneic (allo)HSCT maintenance setting for patients with B-cell (CD19+) malignancies (ALL, NHL) who were transplanted using posttransplant cyclophosphamide (Cy) platform (cyclophosphamide only on day +3 and +4 or cyclophosphamide on day +3 and +4, mycophenolate mofetil [MMF] day 1-35, tacrolimus or sirolimus from day +5) improves disease-free survival (DFS) in an expanded cohort of patients, separately for ALL and NHL cohorts. (Phase II)

SECONDARY OBJECTIVES:

I. Determine the safety and toxicity of incorporating blinatumomab into the post-allogeneic hematopoietic stem cell transplant (HSCT) maintenance setting for patients with CD19+-B-cell malignancies (acute lymphoblastic leukemia [ALL], non-Hodgkin’s lymphoma [NHL]). (Phase II)

II. To report non-relapse mortality (NRM). (Phase IB/II)

III. To report the progression-free survival (PFS), disease-free survival (DFS), and overall survival (OS) after transplant for all patients and according to disease type (B-precursor ALL versus NHL). (Phase IB/II)

IV. To report on minimal residual disease (MRD) status as measured by flow cytometry and/or molecular markers. The proportion of patients who convert from MRD to no MRD status after treatment will be reported. (Phase IB/II)

EXPLORATORY OBJECTIVE:

I. To examine the T cell subsets in the peripheral blood (PB) and bone marrow (BM) using multicolor flow cytometry and T cell repertoire sequencing before and after treatment with blinatumomab. (Phase IB/II)

OUTLINE:

Patients receive blinatumomab intravenously (IV) continuously on days 1-28. Patients with detectable leukemia or lymphoma before or after their stem cell transplant are eligible for a second cycle of blinatumomab IV continuously for 28 days, which begins no sooner than 42 days and no later than 70 days from day 1 of the first cycle.

After completion of study treatment, patients are followed up periodically for 2 years.

Trial Phase Phase I/II

Trial Type Treatment

Lead Organization
Johns Hopkins University / Sidney Kimmel Cancer Center

Principal Investigator
Jonathan Allen Webster

  • Primary ID J1713
  • Secondary IDs NCI-2019-00402, IRB00125679, CRMS-65830
  • Clinicaltrials.gov ID NCT03114865