Clinical Trials /

A Study of Blinatumomab in Patients With Pre B-cell ALL and B-cell NHL as Post-allo-HSCT Remission Maintenance

NCT03114865

Description:

The investigators primary objective is to 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]).

Related Conditions:
  • B-Cell Acute Lymphoblastic Leukemia
  • Non-Hodgkin Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study of Blinatumomab in Patients With Pre B-cell ALL and B-cell NHL as Post-allo-HSCT Remission Maintenance
  • Official Title: A Pilot Study of Blinatumomab in Patients With Pre B-cell Acute Lymphoblastic Leukemia (ALL) and B-cell Non-Hodgkin Lymphoma (NHL) as Post-allogeneic Stem Cell Transplant (Allo-HSCT) Remission Maintenance

Clinical Trial IDs

  • ORG STUDY ID: J1713
  • SECONDARY ID: IRB00125679
  • NCT ID: NCT03114865

Conditions

  • Acute Lymphoblastic Leukemia
  • B-cell Non Hodgkin Lymphoma
  • Pre B-Cell Acute Lymphoblastic Leukaemia

Interventions

DrugSynonymsArms
BlinatumomabBlincytoPost-alloHSCT Maintenance
BlinatumomabBlincytoPost-alloHSCT Maintenance
BlinatumomabBlincytoPost-alloHSCT Maintenance
DexamethasonePost-alloHSCT Maintenance

Purpose

The investigators primary objective is to 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]).

Trial Arms

NameTypeDescriptionInterventions
Post-alloHSCT MaintenanceExperimentalBlinatumomab will be administered as a continuous intravenous (IV) infusion over four weeks followed by a two-week treatment free interval. It is recommended that patients are hospitalized at least during the first three days of the first cycle and the first two days of the second cycles.
  • Blinatumomab
  • Blinatumomab
  • Blinatumomab
  • Dexamethasone

Eligibility Criteria

        Inclusion Criteria:

          -  Pre-B ALL, low and high grade NHL who underwent an alloHSCT using posttransplant CY
             GVHD prophylaxis (Pt-Cy alone or combination with MMF/tacrolimus or sirolimus) as
             follows:

               -  Pre-B ALL patients in CR1 with high-risk features such as adverse cytogenetics
                  including t(9;22), t(4;11) or other MLL rearrangements, t(8;14), complex
                  karyotype (≥5 chromosomal abnormalities), hypodiploidy (<44 chromosomes), low
                  hypodiploidy (30-39 chromosomes)/near triploidy (60-68 chromosomes), high 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 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 (ANC >1 x109/L, and non-transfused platelets >30x109/L) and
             no evidence of disease progression

          -  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

          -  Age ≥18 years

          -  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 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 within a week 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 active acute GVHD (grade 2-4) and active moderate or severe chronic GVHD
             with GVHD therapy initiation or escalation within 28 days. Patients who required
             steroids for the treatment of GVHD will need to be off steroids for at least 2 weeks
             before enrollment. (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 2 weeks prior to study enrollment.

          -  Inadequate end organ function defined as AST, ALT, and alkaline phosphatase > 3X ULN,
             bilirubin >=1.5X ULN, or creatinine >=2 mg/dL

          -  Patients with Ph-positive ALL who are eligible for post-transplant 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 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 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)
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall survival at two years post first treatment cycle
Time Frame:2 years
Safety Issue:
Description:Percentage of enrolled participants who receive BMT and Blinatumomab and are alive at two years post BMT.

Secondary Outcome Measures

Measure:Non-Relapse Mortality
Time Frame:2 years
Safety Issue:
Description:Percentage of participants who experience non-relapse mortality after 2 years.
Measure:Progression-free survival
Time Frame:2 years
Safety Issue:
Description:Percentage of participants who experience progression-free survival after 2 years.
Measure:Disease-free Survival
Time Frame:2 years
Safety Issue:
Description:Percentage of participants who experience disease-free survival after 2 years.
Measure:Overall Survival
Time Frame:2 years
Safety Issue:
Description:Percentage of participants who experience overall survival after 2 years.
Measure:Minimal Residual Disease
Time Frame:2 years
Safety Issue:
Description:Percentage of participants who convert from MRD to no MRD after treatment.

Details

Phase:Early Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Trial Keywords

  • bone marrow
  • bone marrow transplant
  • allogeneic
  • tacrolimus
  • cyclophosphamide
  • Blinatumomab

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