RECRUITING

Blinatumomab After TCR Alpha Beta/CD19 Depleted HCT

Conditions

B-cell Acute Lymphoblastic Leukemia B-cell Childhood Acute Lymphoblastic Leukemia B-Cell ALL, Childhood

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

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

Quick Facts

Study Start:2021-02-01

Study Completion:2029-12-31

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT04746209

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:Not specified to 25 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:CHILD, ADULT

Inclusion Criteria	Exclusion 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	* 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.

Inclusion Criteria

Exclusion 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

* 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.

Contacts and Locations

Study Contact

Meredith Beversdorf, RN

CONTACT

414-266-5891

mbeversdorf@chw.org

Emily Ruszkiewicz, BS

CONTACT

414-266-4092

eruszkiewicz@mcw.edu

Principal Investigator

Rachel Phelan, MD, MPH

PRINCIPAL_INVESTIGATOR

Medical College of Wisconsin

Study Locations (Sites)

Children's Hospital of Wisconsin

Milwaukee, Wisconsin, 53226

United States

Collaborators and Investigators

Sponsor: Medical College of Wisconsin

Rachel Phelan, MD, MPH, PRINCIPAL_INVESTIGATOR, Medical College of Wisconsin

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2021-02-01

Study Completion Date2029-12-31

Study Record Updates

Study Start Date2021-02-01

Study Completion Date2029-12-31

Terms related to this study

Additional Relevant MeSH Terms

B-cell Acute Lymphoblastic Leukemia
B-cell Childhood Acute Lymphoblastic Leukemia
B-Cell ALL, Childhood