B-Cell Acute Lymphoblastic LeukaemiaPhase 1NCT03751709
Blinatumomab Plus HLA-Mismatched Cellular Therapy for Relapsed/Refractory CD19+ ALL
A Phase 1 study testing Blinatumomab and Haplo-Mismatched Cell Therapy (HMCT) in people with B-Cell Acute Lymphoblastic Leukaemia and ALL, Adult, run by Cedars-Sinai Medical Center at 1 site in United States.
Trial summary
Single center Phase 1 dose escalation trial of the combination of standard-of-care blinatumomab plus Haplo-Mismatched Cellular Therapy (HMCT). HMCT refers to the infusion of donor peripheral blood mononuclear cells collected via pheresis from a haploidentical family member - the procedure is analogous to giving a… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- B-Cell Acute Lymphoblastic Leukaemia, ALL, Adult, B-ALL
- What is being tested?
- Blinatumomab and Haplo-Mismatched Cell Therapy (HMCT)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 1 siteUnited States
- Study dates
- 14 Feb 2020to 12 Nov 2024
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Relapsed/Refractory CD19+ Acute Lymphoblastic Leukemia. Patients with minimal residual disease detected by NGS > 10e-6 or multiparameter flow cytometry > 10e-5 in blood or bone marrow are eligible.
- Patients must belong to one of the following 'high risk' categories: (i) at least 2nd relapse or refractory to at least one salvage therapy (ii) relapse after autologous stem cell transplantation, (iii) any relapse in a patient with no immediate allogeneic transplant option (such as advanced age, comorbidity, lack of identified donor, or patient refusal) (iv) Patients with Ph+ ALL will be allowed on the trial at the discretion of the treating physician if they are no longer candidates for further TKI based therapy. Prior therapy with a minimum of 2 prior 2nd/3rd generation TKI is required. (TKI therapy is not allowed while on trial).
- Patients with prior blinatumomab treatment are eligible if last treatment was at least 3 months prior to C1D1, patient's blasts are confirmed to express CD19, and patient did not develop Grade 4 toxicities with prior blinatumomab therapy.
- Age ≥ 18 years.
- Patient has at least one medically fit first- or second-degree family member who is a potential haploidentical donor. In addition, the prospective donor is willing to voluntarily donate peripheral blood cells, and sign consent forms. For minors, consent will be obtained from parent/guardian (assent from the minor is required).
- Patients must have adequate organ function as defined below (note there are no marrow function criteria, cytopenias will not result in exclusion):
Show all 13Show fewer
- Serum creatinine ≤ 2.0 x the upper limits of institutional normal (ULN)
- Total bilirubin ≤ 1.5x the upper limits of institutional normal, unless elevated bilirubin is attributed to liver involvement of leukemia or Gilbert's disease.
- AST/ALT ≤ 2.5 x the upper limits of institutional normal (≤ 5 x ULN for patients with suspected liver involvement of leukemia).
- ECOG performance status of 0, 1, or 2, and estimated survival of at least 3 months.
- Patients must be able to understand and agree to sign an IRB-approved informed consent form.
- The effects of treatment on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control or complete abstinence) prior to study entry, for the duration of study, and for two months after study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
- Written informed consent obtained from subject and ability for subject to comply with the requirements of the study.
Who cannot join
- Prior allogeneic stem cell transplant
- Prior treatment with fludarabine or cladribine within the last six months prior to C1D1, or treatment with antithymocyte globulin (ATG) or alemtuzumab within the last 1 year.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Pregnant and/or lactating.
- Who have had non-biopsy surgery in the last 10 days.
- Who have active CNS disease. Patients with previously treated leptomeningeal disease without evidence of remaining leukemia cells by spinal fluid will be eligible. Intrathecal chemo may be given for prophylaxis for patients who previously had CNS involvement but have now cleared the CSF, at the discretion of the treating physician. Recommend to avoid IT chemotherapy for a few days before or after HMCT infusion.
Show all 13Show fewer
- History or presence of clinically relevant CNS pathology such as epilepsy, childhood or adult seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis (patients with minor prior stroke who are cognitively intact and capable of performing all ADLs are permitted).
- Patients with known active autoimmune disorder.
- Known infection with HIV virus.
- Patients concurrently taking the following drugs are excluded: mycophenolate, cyclosporine, prednisone > 20mg/day, or immunosuppressive agents (low dose maintenance chemotherapy - POMP, hydroxyurea, low dose prednisone - is allowed until 24 hours prior to starting blinatumomab).
- Patients known to have active hepatitis B or C (Hepatitis B positive patients are allowed if they are on appropriate antiviral agents such as lamivudine).
- Subject likely to not be available to complete all protocol-required study visits or procedures, including follow-up visits, and/or to comply with all required study procedures to the best of the subject and Investigator's knowledge.
- History or evidence of any other clinically significant disorder, condition or disease (with the exception of those outlined above) that, in the opinion of the Investigator or Amgen physician, if consulted, would pose a risk to subject safety or interfere with the study evaluation, procedures or completion.
Trial locations and contacts
1 site in 1 country.
United States1 site
Cedars-Sinai Medical Center
Los Angeles, California, 90048
About this study
Official title: IIT2017-05-MERIN-BLINHMCT: Blinatumomab Plus HLA-Mismatched Cellular Therapy (HMCT) for Relapsed/Refractory CD19+ ALL
Single center Phase 1 dose escalation trial of the combination of standard-of-care blinatumomab plus Haplo-Mismatched Cellular Therapy (HMCT). HMCT refers to the infusion of donor peripheral blood mononuclear cells collected via pheresis from a haploidentical family member - the procedure is analogous to giving a donor lymphocyte infusion outside of the setting of an allogeneic stem cell transplant; also known as 'microtransplantation'. The HMCT is an unselected mix of lymphocytes and leukocytes, but the product dose escalation will be done based on the T cell content.
Ten recipients are planned. Each subject will be administered one infusion of HMCT during the first cycle of blinatumomab and two infusions during cycle two of blinatumomab; the CD3+ cell dose of the HMCT infusion is governed by dose escalation / de-escalation following a Bayesian method.
Read the detailed description
This single center, phase 1 study will examine the safety, side effects, and effectiveness of combining the investigational use of Haplo-Mismatched Cellular Therapy (HMCT) in combination with blinatumomab. Investigators plan to give HMCT starting on day 15, after the initial CRS caused by blinatumomab has resolved. The investigational treatment will start with 1% of the typical HMCT dose (10e6 CD3+ cells/kg) and will employ a modified dose escalation design as an additional safety measure. The primary end points will be DLT of the combination of blinatumomab and HMCT.
- Conditions
- B-Cell Acute Lymphoblastic Leukaemia, ALL, Adult, B-ALL
- Being tested
- Blinatumomab, Haplo-Mismatched Cell Therapy (HMCT)
- Keywords
- Haplo-Mismatched Cellular Therapy, Acute Lymphoblastic Leukemia, ALL, B-ALL, donor lymphocyte, DLI, blinatumomab, bispecific, microtransplantation, microtransplant
- Medical subject headings
- Burkitt Lymphoma, Precursor Cell Lymphoblastic Leukemia-Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BlinatumomabDrug
Also called Blincyto
Blinatumomab per package insert - via continuous infusion days 1-28 of Cycle 1 and Cycle 2, every 42 days.
Haplo-Mismatched Cell Therapy (HMCT)Other
Also called HMCT; 'primary DLI; 'microtransplantation'
HMCT infusion Cycle 1, Day 15 and Cycle 2, Day 8 \& Day 15
| Study group | Role | What they receive |
|---|---|---|
| Subjects | Experimental | Blinatumomab+Haplo-Mismatched Cell Therapy (HMCT) Receives: Drug: Blinatumomab; Other: Haplo-Mismatched Cell Therapy (HMCT) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of DLTs
Number of Dose Limiting Toxicities experienced by patients undergoing HLA mismatched cellular therapy (HMCT) of allogenic CD3+ cells in combination with blinatumomab.
Measured: up to 6 months
Secondary outcomes (5)
Number of participants experiencing complete response (CR) from time of transplant to one day following the second treatment
Bone marrow aspiration and local peripheral blood counts will be used to measure response. CR is defined as the following:
- Less than or equal to 5% blasts in the bone marrow
- No evidence of disease, AND
- Full recovery of peripheral blood counts: platelets > 100,000/ul, and ANC > 1000/ul
Measured: up to 3 months
Number of participants experiencing complete response with partial recovery of peripheral blood counts (CRh) from time of transplant to one day following the second treatment
Bone marrow aspiration and local peripheral blood counts will be used to measure response. CRh is defined as the following:
- Less than or equal to 5% blasts in the bone marrow
- No evidence of disease, AND
- Full recovery of peripheral blood counts: platelets > 50,000/ul, and ANC > 500/ul
Measured: up to 3 months
Number of participants experiencing complete response with incomplete count recovery (CRi) from time of transplant to one day following the second treatment
Bone marrow aspiration and local peripheral blood counts will be used to measure response. CRi is defined as the following:
- Less than or equal to 5% blasts in the bone marrow
- No evidence of disease, AND
- Full recovery of peripheral blood counts: platelets > 100,000/ul, and ANC > 1000/ul
Measured: up to 3 months
Response blast-free hypoplastic or aplastic bone marrow from time of transplant to one day following the second treatment
Bone marrow aspiration and local peripheral blood counts will be used to measure response. Blast-free hypoplastic or aplastic bone marrow response is defined as the following:
- Less than or equal to 5% blasts in the bone marrow
- No evidence of disease, AND
- Full recovery of peripheral blood counts: platelets > 50,000/ul, and ANC > 500/ul
Measured: up to 3 months
Disease burden measured as the minimal residual disease (MRD) response from time of transplant to one day following the second treatment
MRD remission is defined as the occurrence of an MRD level below 10^-4 measured by quantitative reverse transcription polymerase chain reaction (PCR) or flow cytometry.
Complete response defined as: no detectable leukemic cells by PCR or flow cytometry.
Measured: up to 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Nov 2018
- Study start14 Feb 2020
- Primary completion27 Mar 2023
- Study completion12 Nov 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for B-Cell Acute Lymphoblastic LeukaemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cedars-Sinai Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Amgen
- Responsible party
- Principal investigator, Noah Merin, Cedars-Sinai Medical Center
- Investigators
- Noah Merin, MD PhD, Principal investigator, Cedars-Sinai Medical Center Samuel Oschin Comprehensive Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03751709
- Sponsor's protocol ID
- IIT2017-05-MERIN-BLINHMCT
- Status last verified
- Feb 2025
- First submitted
- 19 Nov 2018
- Last updated
- 5 Feb 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- IIT2017-05-MERIN-BLINHMCT: Blinatumomab Plus HLA-Mismatched Cellular Therapy (HMCT) for Relapsed/Refractory CD19+ ALL
- ClinicalTrials.gov ID
- NCT03751709
- Acronym / sponsor ID
- IIT2017-05-MERIN-BLINHMCT
- Conditions
- B-Cell Acute Lymphoblastic Leukaemia, ALL, Adult, B-ALL
- Keywords
- Haplo-Mismatched Cellular Therapy, Acute Lymphoblastic Leukemia, ALL, B-ALL, donor lymphocyte, DLI, blinatumomab, bispecific
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22 participants (actual)
- Lead sponsor
- Cedars-Sinai Medical CenterUniversity, hospital or other
- Collaborators
- Amgen
- Study start
- 14 Feb 2020 (actual)
- Primary completion
- 27 Mar 2023 (actual)
- Study completion
- 12 Nov 2024 (actual)
- First posted
- 23 Nov 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Single center Phase 1 dose escalation trial of the combination of standard-of-care blinatumomab plus Haplo-Mismatched Cellular Therapy (HMCT). HMCT refers to the infusion of donor peripheral blood mononuclear cells collected via pheresis from a haploidentical family member - the procedure is analogous to giving a donor lymphocyte infusion outside of the setting of an allogeneic stem cell transplant; also known as 'microtransplantation'. The HMCT is an unselected mix of lymphocytes and leukocytes, but the product dose escalation will be done based on the T cell content.
Ten recipients are planned. Each subject will be administered one infusion of HMCT during the first cycle of blinatumomab and two infusions during cycle two of blinatumomab; the CD3+ cell dose of the HMCT infusion is governed by dose escalation / de-escalation following a Bayesian method.
Detailed description
This single center, phase 1 study will examine the safety, side effects, and effectiveness of combining the investigational use of Haplo-Mismatched Cellular Therapy (HMCT) in combination with blinatumomab. Investigators plan to give HMCT starting on day 15, after the initial CRS caused by blinatumomab has resolved. The investigational treatment will start with 1% of the typical HMCT dose (10e6 CD3+ cells/kg) and will employ a modified dose escalation design as an additional safety measure. The primary end points will be DLT of the combination of blinatumomab and HMCT.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Subjects | Experimental | Drug: Blinatumomab, Other: Haplo-Mismatched Cell Therapy (HMCT)Blinatumomab+Haplo-Mismatched Cell Therapy (HMCT) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Relapsed/Refractory CD19+ Acute Lymphoblastic Leukemia. Patients with minimal residual disease detected by NGS > 10e-6 or multiparameter flow cytometry > 10e-5 in blood or bone marrow are eligible.
- Patients must belong to one of the following 'high risk' categories: (i) at least 2nd relapse or refractory to at least one salvage therapy (ii) relapse after autologous stem cell transplantation, (iii) any relapse in a patient with no immediate allogeneic transplant option (such as advanced age, comorbidity, lack of identified donor, or patient refusal) (iv) Patients with Ph+ ALL will be allowed on the trial at the discretion of the treating physician if they are no longer candidates for further TKI based therapy. Prior therapy with a minimum of 2 prior 2nd/3rd generation TKI is required. (TKI therapy is not allowed while on trial).
- Patients with prior blinatumomab treatment are eligible if last treatment was at least 3 months prior to C1D1, patient's blasts are confirmed to express CD19, and patient did not develop Grade 4 toxicities with prior blinatumomab therapy.
- Age ≥ 18 years.
- Patient has at least one medically fit first- or second-degree family member who is a potential haploidentical donor. In addition, the prospective donor is willing to voluntarily donate peripheral blood cells, and sign consent forms. For minors, consent will be obtained from parent/guardian (assent from the minor is required).
Key exclusion criteria (13 listed)
- Prior allogeneic stem cell transplant
- Prior treatment with fludarabine or cladribine within the last six months prior to C1D1, or treatment with antithymocyte globulin (ATG) or alemtuzumab within the last 1 year.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Pregnant and/or lactating.
- Who have had non-biopsy surgery in the last 10 days.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BlinatumomabAlso: BlincytoBlinatumomab per package insert - via continuous infusion days 1-28 of Cycle 1 and Cycle 2, every 42 days. | Drug | Subjects |
| Haplo-Mismatched Cell Therapy (HMCT)Also: HMCT; 'primary DLI; 'microtransplantation'HMCT infusion Cycle 1, Day 15 and Cycle 2, Day 8 \& Day 15 | Other | Subjects |
Primary outcome
Incidence of DLTs
Time frame: up to 6 months
Number of Dose Limiting Toxicities experienced by patients undergoing HLA mismatched cellular therapy (HMCT) of allogenic CD3+ cells in combination with blinatumomab.
5 secondary outcomes
Number of participants experiencing complete response (CR) from time of transplant to one day following the second treatment
Time frame: up to 3 months
Number of participants experiencing complete response with partial recovery of peripheral blood counts (CRh) from time of transplant to one day following the second treatment
Time frame: up to 3 months
Number of participants experiencing complete response with incomplete count recovery (CRi) from time of transplant to one day following the second treatment
Time frame: up to 3 months
Response blast-free hypoplastic or aplastic bone marrow from time of transplant to one day following the second treatment
Time frame: up to 3 months
Disease burden measured as the minimal residual disease (MRD) response from time of transplant to one day following the second treatment
Time frame: up to 3 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Feb 2025.
Related trials for B-Cell Acute Lymphoblastic Leukaemia
RecruitingPhase 1
Anti-CRLF2-R/TSLPR Chimeric Antigen Receptor T Cells (TSLPR-CART) in Participants With Recurrent or Refractory CRLF2-R/TSLPR-Overexpressing B-Cell Acute Lymphoblastic Leukemia (B-ALL)
B-All, Acute Lymphoblastic Leukemia
RecruitingObservational study
Collecting Blood Samples From Patients With and Without Cancer to Evaluate Tests for Early Cancer Detection
Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia
RecruitingObservational study
A Multi-site Study to Evaluate the Persistence of Protective Immunity to Routine Childhood Vaccinations in Participants With B-ALL/Ly Who Have Received Blinatumomab
B-Cell ALL, B-Cell Acute Lymphoblastic Leukaemia
RecruitingObservational study
Tissue, Blood, and Body Fluid Sample Collection From Patients With Hematologic Cancer
Chronic Myeloproliferative Disorders, Leukemia
Recruiting
A Multicenter Study to Evaluate Next-Generation Sequencing (NGS) Testing and Monitoring of B-Cell Recovery to Guide Management Following Chimeric Antigen Receptor T-cell (CART) Induced Remission in Children and Young Adults With B Lineage Acute Lymph...
B-All, Acute Lymphoblastic Leukemia
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Noah Merin, MD PhD principal investigator
Cedars-Sinai Medical Center Samuel Oschin Comprehensive Cancer Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Blinatumomab and Haplo-Mismatched Cell Therapy (HMCT) in people with B-Cell Acute Lymphoblastic Leukaemia and ALL, Adult, run by Cedars-Sinai Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of DLTs (time frame: up to 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Feb 2025.