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

NCT03114865 | Active Not Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: J1713IRB00125679
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

Brief Summary

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 \[NHL\]).

Conditions

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

Keywords

bone marrow; bone marrow transplant; allogeneic; tacrolimus; cyclophosphamide; Blinatumomab

Outcome Measures

Primary Outcomes (1)

• Overall survival at two years post first treatment cycle

  Percentage of enrolled participants who receive BMT and Blinatumomab and are alive at two years post BMT.

  2 years

Secondary Outcomes (5)

• Non-Relapse Mortality

  2 years

• Progression-free survival

  2 years

• Disease-free Survival

  2 years

• Overall Survival

  2 years

• Minimal Residual Disease

  2 years

Study Arms (1)

Post-alloHSCT Maintenance

EXPERIMENTAL

Blinatumomab 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.

Drug: Blinatumomab 9ug; Drug: Blinatumomab 28 ug; Drug: Blinatumomab; Drug: Dexamethasone

Interventions

Blinatumomab 9ug DRUG

Cycle 1 - Days 1-7: 9 ug/day IV daily

Also known as: Blincyto

Post-alloHSCT Maintenance

Blinatumomab 28 ug DRUG

Cycle 1 - Days 8-28: 28 ug/day IV daily

Also known as: Blincyto

Post-alloHSCT Maintenance

Blinatumomab DRUG

Cycle 2 - Days 1-28: 28 ug/day IV daily

Also known as: Blincyto

Post-alloHSCT Maintenance

Dexamethasone DRUG

Day 1 of Cycle 1 and 2, prior to a step dose (such as cycle 1 day 8), or when restarting an infusion after an interruption of 4 hours or more: 20 mg IV

Post-alloHSCT Maintenance

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• A. Pre-B ALL patients in CR1 with high-risk features such as adverse cytogenetics including t(9;22) or 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 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 B. 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.

You may not qualify if:

• 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 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.
• 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

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• Amgen: collaborator

Study Sites (1)

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21287, United States

Location

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Lymphoma, B-Cell; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma

Interventions

blinatumomab; Dexamethasone

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, Non-Hodgkin; Lymphoma

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Ivana Gojo, MD

  Johns Hopkins University

  STUDY CHAIR

• Jonathan Webster, MD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 11, 2017
• First Posted: April 14, 2017
• Study Start: September 5, 2017
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): June 30, 2026
• Last Updated: May 22, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)