Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Blinatumomab After TCR Alpha Beta/CD19 Depleted HCT

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04746209
Recruitment Status : Recruiting
First Posted : February 9, 2021
Last Update Posted : September 17, 2021
Sponsor:
Collaborators:
Amgen
University of Wisconsin, Madison
Information provided by (Responsible Party):
Rachel Phelan, Medical College of Wisconsin

Brief Summary:
This trial will assess the feasibility of alpha/beta T-cell and B-cell depleted allogeneic hematopoietic cell transplantation (HCT) followed by blinatumomab therapy for high-risk B cell acute lymphoblastic leukemia (ALL) as a means of reducing rates of subsequent relapse and improving survival, while also minimizing treatment-related morbidity/ mortality and late effects. The conditioning regimens will be dependent on the patient's minimal residual disease (MRD) status prior to HCT using high throughput sequencing.

Condition or disease Intervention/treatment Phase
B-cell Acute Lymphoblastic Leukemia B-cell Childhood Acute Lymphoblastic Leukemia B-Cell ALL, Childhood Device: Alpha/Beta T-cell and B-cell depleted HCT Drug: Blinatumomab Phase 2

Detailed Description:
This trial evaluates the ability of a biologically active therapy in blinatumomab, an anti-CD19/CD3 bispecific T-cell engager, to further reduce the risk of leukemia relapse following HCT to improve post-HCT outcomes. The investigators will also utilize an alpha-beta T-cell and B-cell depleted graft to reduce the risk of GVHD along with a reduced intensity conditioning regimen without the use of TBI in patients who are minimal residual disease (MRD) negative using high throughput sequencing (HTS) prior to HCT. For those patients who remain HTS-MRD positive, a myeloablative conditioning regimen will be utilized, also followed by blinatumomab. This multi-institutional pilot study will be limited to 25 (estimated 10-15 per stratum) evaluable children, adolescents and young adults with B-ALL, that have experienced a relapse or have high-risk disease.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 25 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Alpha/Beta T-cell and B-cell Depleted Allogeneic Transplantation (IDE 13641) Followed by Blinatumomab Therapy for High-Risk B-Acute Lymphoblastic Leukemia: A Pilot Study
Actual Study Start Date : February 1, 2021
Estimated Primary Completion Date : February 28, 2024
Estimated Study Completion Date : December 31, 2029


Arm Intervention/treatment
Experimental: Alpha/beta T-cell and B-cell Depleted, Myeloablative HCT
Patients who are MRD Negative by Flow cytometry but are MRD Positive by High Throughput Sequencing, will receive a myeloablative conditioning regimen which includes total body irradiation (TBI) followed by an alpha/beta T-cell and B-cell depleted transplant. They will also receive a 28 day continuous infusion of blinatumomab starting on Day 100 post-transplant in the absence of significant ongoing GVHD.
Device: Alpha/Beta T-cell and B-cell depleted HCT
Device: Alpha/Beta T-cell and B-cell depletion

Drug: Blinatumomab
28 day continuous infusion given on Day 100 post-HCT if no significant ongoing GVHD
Other Name: Blincyto

Experimental: Alpha/beta T-cell and B-cell Depleted, Reduced Intensity HCT
Patients who are MRD Negative by Flow cytometry and are MRD Negative by High Throughput Sequencing, will receive a reduced intensity conditioning regimen followed by an alpha/beta T-cell and B-cell depleted transplant. They will also receive a 28 day continuous infusion of blinatumomab starting on Day 100 post-transplant in the absence of significant ongoing GVHD.
Device: Alpha/Beta T-cell and B-cell depleted HCT
Device: Alpha/Beta T-cell and B-cell depletion

Drug: Blinatumomab
28 day continuous infusion given on Day 100 post-HCT if no significant ongoing GVHD
Other Name: Blincyto




Primary Outcome Measures :
  1. Percentage of patients who are able to receive the blinatumomab infusion [Feasibility] [ Time Frame: Day +100 post-HCT ]
    Percentage of patients who are able to receive the blinatumomab infusion at day +100 post-HCT and complete a minimum of 14/28 planned days


Secondary Outcome Measures :
  1. Cumulative incidence of treatment-related adverse events [Tolerability] [ Time Frame: Day of HCT to Day +180 post-HCT ]
    As defined by cumulative incidence of treatment-related adverse events of blinatumomab post-HCT

  2. Overall Survival [ Time Frame: Day of HCT to 1 year post-HCT ]
    Defined as the time interval from the date of transplant to death or last follow up

  3. Disease Free Survival [ Time Frame: Day of HCT to 1 year post-HCT ]
    Defined as the time interval from the date of transplant to death or last follow up or disease relapse

  4. Engraftment [ Time Frame: Day +100 and +1 year post-HCT ]
    Defined as the number of patients who achieve ANC > 500/uL for 3 consecutive days

  5. Primary Graft Failure [ Time Frame: Day +28 and + 1 year post-HCT ]
    is defined as failure to achieve ANC > 500/uL by Day +28

  6. Secondary Graft Failure [ Time Frame: Day +28 and +1 year post-HCT ]
    Patients who initially achieve neutrophil engraftment followed by a decline in ANC < 500/uL that is unresponsive to growth factor therapy

  7. Treatment Related Mortality [ Time Frame: Day of HCT to Day +100 and 1 year post-HCT ]
    Defined as death occurring in a patient from causes other than disease relapse or progression

  8. Acute & Chronic GVHD [ Time Frame: Day +100, +180 and 1 year post-HCT ]
    Incidences of Grades 2-4 and Grades 3-4 acute GVHD

  9. Patient Reported Outcomes [ Time Frame: Baseline, Day +100, +180, +1 year post-HCT ]
    PROMIS Pediatric/Parent Proxy Profile 25 (either pediatric self-report if age 8-17 or parent proxy if age 5-8, or both if feasible) or PROMIS-29 Profile if age 18 or older

  10. Length of Stay [ Time Frame: Number of days between the day of transplantation, Day 0, and Day +180 post-HCT ]
    Define by the total number of days a patient spends in the hospital

  11. Persistence of Minimal Residual Disease (MRD) Negativity [ Time Frame: Days +28, +100, +180 and +1 year post-HCT ]
    Number of patients remaining MRD negative by flow cytometry and/or high throughput sequencing

  12. Relapse [ Time Frame: Day of HCT to day +180 and 1 year post-HCT ]
    Cumulative incidence of relapse in all patients


Other Outcome Measures:
  1. Analysis of immune cell phenotyping [ Time Frame: Days +19, +91, +135 and +180 post-HCT ]
    Reconstitution of T, B, and NK cell subsets in the peripheral blood will be analyzed by immune cell phenotyping using flow cytometry.

  2. Functional assessment of lymphocyte subsets [ Time Frame: Days +19, +91, +135 and +180 post-HCT ]
    To assess lymphocyte function, peripheral blood mononuclear cells will be co-cultured with stimulator cells in the presence or absence of blinatumomab.

  3. Serum cytokine analysis [ Time Frame: Days +19, +91, +135 and +180 post-HCT ]
    Plasma cytokines will be measured to examine pro and anti-inflammatory cytokines, chemokines and growth factors produced by donor cells during immune reconstitution and GVHD. The plasma cytokines Eotaxin, Eotaxin-3, GM-CSF, IFN-γ, IL-10, IL-12p70, IL-12/IL-23p40, IL-13, IL-15, IL-16, IL-17A, IL-1α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IP-10, MCP-1, MCP-4, MDC, MIP-1α, MIP-1β, TARC, TNF-α, TNF-β, VEGF-A, and IL-8 will be measured using a multiplex cytokine analyzer where 10 antibodies specific for the above cytokines are attached to a single well providing cytokine capture and immune specificity.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   up to 25 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of B-ALL with no evidence of minimal residual disease in the bone marrow by multi-parameter flow cytometry (FC-MRD negative, <0.01%) and meet at least one of the following:

    1. In remission after first relapse or greater (≥ CR2)
    2. Very-high risk biology ALL that is proceeding to HCT in first remission (e.g. Induction failure, Severe-hypodiploidy, Ph-like ALL)
    3. First remission with persistent disease identified as end of consolidation (EOC) MRD > 0.01%.
  • Patients must have an available unrelated or haploidentical donor
  • Age ≤ 25 years at time of study enrollment
  • Karnofsky Performance Status ≥ 60% for patients 16 years and older and Lansky Play Score ≥ 60 for patients under 16 years of age
  • Have acceptable organ function as defined within 14 days of study registration: Renal: creatinine clearance or radioisotope GFR ≥ 60 mL/min/1.73m2 Hepatic: ALT < 5 x upper limit of normal (ULN) and total bilirubin ≤ 3 mg/dL Cardiac: left ventricular ejection fraction ≥ 40% by ECHO/MUGA Pulmonary: No evidence of dyspnea at rest. No supplemental oxygen requirement. If measured, carbon monoxide diffusion capacity (DLCO) > 50%. Central Nervous System: Based on clinical exam, no concern for/evidence of active CNS infection. Patients with fully treated prior CNS infections are eligible. Patients with seizure disorders may be enrolled if seizures are well-controlled on anticonvulsant therapy.
  • Patients who have experienced their relapse after HCT are eligible, provided they have no evidence of acute or chronic Graft-versus-Host Disease (GVHD) and are off all transplant immune suppression therapy for at least 7-days (e.g. steroids, cyclosporine, tacrolimus). Steroid therapy for non-GVHD and/or non-leukemia therapy is acceptable.
  • Immunotherapy: At least 42 days after the completion of any type of immunotherapy aside from blinatumomab (e.g. tumor vaccines or CAR T-cell therapy).
  • XRT: Cranial or craniospinal XRT is prohibited during protocol therapy. ≥ 90 days must have elapsed if prior TBI, cranial or craniospinal XRT
  • Sexually active females of child bearing potential must agree to use adequate contraception (diaphragm, birth control pills, injections, intrauterine device [IUD], surgical sterilization, subcutaneous implants, or abstinence, etc.) for the duration of treatment and for 2 months after the completion of blinatumomab therapy. Sexually active men must agree to use barrier contraceptive for the duration of treatment and for 2 months after the completion of blinatumomab therapy.
  • Voluntary written consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.
  • All patients enrolled in this study must have been enrolled in the Blinatumomab Bridging Therapy (BBT) Trial

Exclusion Criteria:

  • Active extramedullary disease or presence of chloromatous disease.
  • Receiving concomitant chemotherapy, radiation therapy; immunotherapy or other anti-cancer therapy for treatment of disease other than is specified in the protocol.
  • Systemic fungal, bacterial, viral, or other infection not controlled (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment). Patients with possible fungal infections must have had at least 2 weeks of appropriate anti-fungal antibiotics and be asymptomatic.
  • Pregnant or lactating. The agents used in this study are known to be teratogenic to a fetus and there is no information on the excretion of agents into breast milk. All females of childbearing potential must have a blood test or urine study within 7 days prior to registration to rule out pregnancy.
  • Known allergy to any chemotherapies or targeted agents included in this protocol.
  • Participating in a concomitant Phase 1 or 2 study involving treatment of disease.
  • Active malignancy other than B-ALL.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04746209


Contacts
Layout table for location contacts
Contact: Meredith Beversdorf, RN 414-266-5891 mbeversdorf@chw.org
Contact: Emily Ruszkiewicz, BS 414-266-4092 eruszkiewicz@mcw.edu

Locations
Layout table for location information
United States, Wisconsin
Children's Hospital of Wisconsin Recruiting
Milwaukee, Wisconsin, United States, 53226
Contact: Meredith Beversdorf, RN    414-266-5891    mbeversdorf@chw.org   
Contact: Emily Ruszkiewicz, BS    414-266-4092    eruszkiewicz@mcw.edu   
Principal Investigator: Rachel Phelan, MD, MPH         
Sub-Investigator: Julie-An Talano, MD         
Sponsors and Collaborators
Medical College of Wisconsin
Amgen
University of Wisconsin, Madison
Investigators
Layout table for investigator information
Principal Investigator: Rachel Phelan, MD, MPH Medical College of Wisconsin
Layout table for additonal information
Responsible Party: Rachel Phelan, Associate Professor, Department of Pediatrics, Division of Hematology/Oncology/BMT, Medical College of Wisconsin
ClinicalTrials.gov Identifier: NCT04746209    
Other Study ID Numbers: Blina Part 2
First Posted: February 9, 2021    Key Record Dates
Last Update Posted: September 17, 2021
Last Verified: September 2021

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: Yes
Additional relevant MeSH terms:
Layout table for MeSH terms
Leukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Blinatumomab
Antineoplastic Agents