Leukemia, LymphoidPhase 1FluBuATGNCT02916979
Myeloid-Derived Suppressor Cells and Checkpoint Immune Regulators' Expression in Allogeneic SCT Using FluBuATG
A Phase 1 study testing Fludarabine, Busulfan and Rabbit ATG in people with Leukemia, Lymphoid and Leukemia, Myeloid, run by Dartmouth-Hitchcock Medical Center at 1 site in United States.
Trial summary
This study is examining a chemotherapy regimen and immune suppressive medications in the setting of an allogeneic stem cell transplant. A pilot clinical trial to characterize the incidence, prevalence and function of myeloid-derived suppressor cells (MDSCs) and immune checkpoint regulators (V-domain Ig Suppressor of… Read more about this study
- Who is it for?
- Ages 18 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Leukemia, Lymphoid, Leukemia, Myeloid, Myelodysplastic Syndromes
- What is being tested?
- Fludarabine, Busulfan and Rabbit ATG
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- 6 Sep 2016to 11 Feb 2022
- 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 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Age less than or equal to 75 years
- The patient must be approved for transplant by the treating transplant physician. This includes completion of their pretransplant workup, as directed by standard Dartmouth-Hitchcock Medical Center (DHMC) Standard Operating Procedures (SOPs). DHMC SOP for Pretransplant Evaluation of allogeneic recipient.
- The patient must have a disease, listed below, with treatment responsiveness that the treating transplant physician believes will benefit from an allogeneic stem cell transplant. The diseases include:
- Acute leukemia AML (Acute Myeloid Leukemia), ALL (Acute Lymphoid Leukemia)
- Chronic leukemia CML (Chronic Myeloid Leukemia), CLL (Chronic Lymphoid Leukemia)
- Myelodysplasia
Show all 21Show fewer
- Myelofibrosis
- Lymphoma NHL (Non-Hodgkin's Lymphoma) and Hodgkin's disease
- Plasma cell disorder, including myeloma, Waldenstrom's Macroglobulinemia
- Donor availability- the patient must have an identified donor
- Sibling Availability of a 6 out of 6 identical donor
- Unrelated donor: Availability of a 6 out of 6 unrelated donor
- No human immunodeficiency virus (HIV) infection or active hepatitis B or C
- Easter Cooperative Oncology Group (ECOG) performance status 0, 1, or 2
- Diffusing capacity of the lungs for carbon monoxide DLCO more than or equal to 40 percent predicted
- Left ventricular ejection fraction more than or equal to 35 percent
- Serum bilirubin less than 2x upper limit of normal transaminases less than 3x normal at the time of transplant
- No active or uncontrollable infection
- In female, a negative pregnancy test if experiencing menstrual periods
- No major organ dysfunction precluding transplantation
- No evidence of an active malignancy that would limit the patient's survival to less than 2 years. If there is any question, the principal investigator can make a decision.
Who cannot join
- Psychiatric disorder or a mental deficiency of the patient that is sufficiently severe to make compliance with the treatment unlikely, and making informed consent impossible.
- Major anticipated illness or organ failure incompatible with survival from bone marrow transplant.
- History of refractory systemic infection
- Donor eligibility
- Human leukocyte antigen (HLA) 6 out of 6 matched related or unrelated donor.
- The donor must be healthy and must be willing to serve as a donor, based on standard guidelines
Show all 16Show fewer
- The donor must have no significant comorbidities that would put the donor at marked increased risk
- There is no age restriction for the donor
- Informed consent must be signed by donor, if sibling donor, or by third party if unrelated donor.
- Donor Exclusion Criteria
- The National Marrow Donor Program (NMDP) guidelines for exclusion criteria will be used. In addition, the following donors are NOT eligible:
- Syngeneic donor
- Pregnant or lactating donor
- Human immunodeficiency virus (HIV) or active HepB or C in the donor
- Donor unfit to receive Granulocyte-colony stimulating factor (GCSF) and undergo apheresis
- A donor with a psychiatric disorder or mental deficiency that makes compliance with the procedure unlikely and informed consent impossible
Trial locations and contacts
1 site in 1 country.
United States1 site
Dartmouth-Hitchcock Medical Center
Lebanon, New Hampshire, 03756
About this study
Official title: A Pilot Trial Examining Myeloid-Derived Suppressor Cells and Checkpoint Immune Regulators' Expression in Allogeneic Stem Cell Transplant Recipients Using Myeloablative Busulfan and Fludarabine
This study is examining a chemotherapy regimen and immune suppressive medications in the setting of an allogeneic stem cell transplant. A pilot clinical trial to characterize the incidence, prevalence and function of myeloid-derived suppressor cells (MDSCs) and immune checkpoint regulators (V-domain Ig Suppressor of T-cell Activation [VISTA], cytotoxic T-lymphocyte- associated protein 4 [CTLA-4], programmed death-ligand 1 [PD-L1]) during early immune recovery following an allogeneic stem cell transplant. The site will use a myeloablative regimen of fludarabine with busulfan, adopted from CALGB 100801, to define clinical endpoints, including engraftment, 100 day survival and one year survival (Objective #1). The site will characterize the incidence, prevalence and function of MDSCs and immune checkpoint regulators in patients' blood and bone marrow following transplantation (Objective #2). The site will correlate these laboratory results with clinical outcomes and the incidence of graft-versus-host disease (GVHD). As an exploratory aim, in those patients experiencing GVHD and requiring treatment, the site will define the MDSCs frequency and checkpoint regulator expression and correlate these results with the patient's response to GVHD therapy.
- Conditions
- Leukemia, Lymphoid, Leukemia, Myeloid, Myelodysplastic Syndromes, Myelofibrosis, Lymphoma, Malignant, Multiple Myeloma
- Being tested
- Fludarabine, Busulfan, Rabbit ATG, Methotrexate
- Medical subject headings
- Leukemia, Lymphoid, Leukemia, Myeloid, Myelodysplastic Syndromes, Primary Myelofibrosis, Lymphoma, Multiple Myeloma, Waldenstrom Macroglobulinemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FludarabineDrug
Fludarabine: 30 mg/m2 daily for 5 days
BusulfanDrug
Busulfan: 100 mg/m2 daily for 4 days
Rabbit ATGBiological
Rabbit ATG:
Related donors: 1.5 mg/kg daily x 2 days (on days -6 and -5) Unrelated donors: 1.5 mg/kg on day - 6 2 mg/kg on day -5 2.5 mg/kg on day -4
MethotrexateDrug
Methotrexate:
Related donors: 5 mg/m2 on days 1, 3 and 6 Unrelated donors: 5 mg/m2 on days 1, 3, 6 and 11
| Study group | Role | What they receive |
|---|---|---|
| Conditioning Regimen | Other | Fludarabine, Busulfan, Rabbit ATG, Methotrexate Receives: Drug: Fludarabine; Drug: Busulfan; Biological: Rabbit ATG; Drug: Methotrexate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of patients who are surviving at 100-Days post-transplant
100-Day survival of patients
Measured: 100 Days
Secondary outcomes (8)
Time to marrow engraftment
Time to marrow engraftment (defined as absolute neutrophil count > 500/mm3 and platelets > 20,000/mcl for three consecutive days (count first day as engraftment)
Measured: 100 Days
Assessing all subjects' response to treatment at 100 days post-transplant
Response to treatment at 100 days using standard international response criteria, based on CIBMTR definitions.
Measured: 100 Days
Assessing all subjects' response to treatment at 1 year post-transplant
Response to treatment at one year using standard international response criteria, based on CIBMTR definitions.
Measured: 365 Days
Assessing all subjects' survival at 1 year post-transplant
One year survival
Measured: 365 Days
Assessing the mortality rate of patients in the first 100 days post-transplant
Treatment-related mortality in the first 100 days
Measured: 100 Days
Assessing the number of treatment-related adverse events
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Measured: 365 Days
Collecting the incidents of GvHD experienced by patients post-transplant
Incidence of acute and chronic GVHD
Measured: 365 Days
Assessing the donor-chimerism at 30, 60 and 90 days post-transplant
Donor-recipient chimerism following transplant at Days 30, 60 and 90.
Measured: 30, 60, and 90 Days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Sep 2016 (estimated)
- Study start6 Sep 2016
- Primary completion7 Jun 2019
- Study completion11 Feb 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Leukemia, LymphoidStudies of the same condition, open and under way.
- More trials run by Dartmouth-Hitchcock Medical CenterThe sponsor's other registered studies.
- 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
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dartmouth-Hitchcock Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Kenneth Meehan, Dartmouth-Hitchcock Medical Center
- Investigators
- Kenneth Meehan, MD, Principal investigator, Dartmouth-Hitchcock Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02916979
- Sponsor's protocol ID
- D16127
- Acronym
- FluBuATG
- Status last verified
- Oct 2023
- First submitted
- 15 Aug 2016
- Last updated
- 18 Oct 2023
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Trial Examining Myeloid-Derived Suppressor Cells and Checkpoint Immune Regulators' Expression in Allogeneic Stem Cell Transplant Recipients Using Myeloablative Busulfan and Fludarabine
- ClinicalTrials.gov ID
- NCT02916979
- Acronym / sponsor ID
- FluBuATG / D16127
- Conditions
- Leukemia, Lymphoid, Leukemia, Myeloid, Myelodysplastic Syndromes, Myelofibrosis, Lymphoma, Malignant, Multiple Myeloma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Dartmouth-Hitchcock Medical CenterUniversity, hospital or other
- Study start
- 6 Sep 2016 (actual)
- Primary completion
- 7 Jun 2019 (actual)
- Study completion
- 11 Feb 2022 (actual)
- First posted
- 28 Sep 2016 (estimated)
- 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.
This study is examining a chemotherapy regimen and immune suppressive medications in the setting of an allogeneic stem cell transplant. A pilot clinical trial to characterize the incidence, prevalence and function of myeloid-derived suppressor cells (MDSCs) and immune checkpoint regulators (V-domain Ig Suppressor of T-cell Activation [VISTA], cytotoxic T-lymphocyte- associated protein 4 [CTLA-4], programmed death-ligand 1 [PD-L1]) during early immune recovery following an allogeneic stem cell transplant. The site will use a myeloablative regimen of fludarabine with busulfan, adopted from CALGB 100801, to define clinical endpoints, including engraftment, 100 day survival and one year survival (Objective #1). The site will characterize the incidence, prevalence and function of MDSCs and immune checkpoint regulators in patients' blood and bone marrow following transplantation (Objective #2). The site will correlate these laboratory results with clinical outcomes and the incidence of graft-versus-host disease (GVHD). As an exploratory aim, in those patients experiencing GVHD and requiring treatment, the site will define the MDSCs frequency and checkpoint regulator expression and correlate these results with the patient's response to GVHD therapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Conditioning Regimen | Other | Drug: Fludarabine, Drug: Busulfan, Biological: Rabbit ATG, Drug: MethotrexateFludarabine, Busulfan, Rabbit ATG, Methotrexate |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- Age less than or equal to 75 years
- The patient must be approved for transplant by the treating transplant physician. This includes completion of their pretransplant workup, as directed by standard Dartmouth-Hitchcock Medical Center (DHMC) Standard Operating Procedures (SOPs). DHMC SOP for Pretransplant Evaluation of allogeneic recipient.
- The patient must have a disease, listed below, with treatment responsiveness that the treating transplant physician believes will benefit from an allogeneic stem cell transplant. The diseases include:
- Donor availability- the patient must have an identified donor
- No human immunodeficiency virus (HIV) infection or active hepatitis B or C
Key exclusion criteria (16 listed)
- Psychiatric disorder or a mental deficiency of the patient that is sufficiently severe to make compliance with the treatment unlikely, and making informed consent impossible.
- Major anticipated illness or organ failure incompatible with survival from bone marrow transplant.
- History of refractory systemic infection
- Donor eligibility
- Human leukocyte antigen (HLA) 6 out of 6 matched related or unrelated donor.
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 |
|---|---|---|
| FludarabineFludarabine: 30 mg/m2 daily for 5 days | Drug | Conditioning Regimen |
| BusulfanBusulfan: 100 mg/m2 daily for 4 days | Drug | Conditioning Regimen |
| Rabbit ATGRabbit ATG: Related donors: 1.5 mg/kg daily x 2 days (on days -6 and -5) Unrelated donors: 1.5 mg/kg on day - 6 2 mg/kg on day -5 2.5 mg/kg on day -4 | Biological | Conditioning Regimen |
| MethotrexateMethotrexate: Related donors: 5 mg/m2 on days 1, 3 and 6 Unrelated donors: 5 mg/m2 on days 1, 3, 6 and 11 | Drug | Conditioning Regimen |
Primary outcome
Number of patients who are surviving at 100-Days post-transplant
Time frame: 100 Days
100-Day survival of patients
8 secondary outcomes
Time to marrow engraftment
Time frame: 100 Days
Assessing all subjects' response to treatment at 100 days post-transplant
Time frame: 100 Days
Assessing all subjects' response to treatment at 1 year post-transplant
Time frame: 365 Days
Assessing all subjects' survival at 1 year post-transplant
Time frame: 365 Days
Assessing the mortality rate of patients in the first 100 days post-transplant
Time frame: 100 Days
Assessing the number of treatment-related adverse events
Time frame: 365 Days
Collecting the incidents of GvHD experienced by patients post-transplant
Time frame: 365 Days
Assessing the donor-chimerism at 30, 60 and 90 days post-transplant
Time frame: 30, 60, and 90 Days
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 18 Oct 2023.
- Individual participant dataSharing planned: No
Related trials for Leukemia, Lymphoid
RecruitingPhase 2/3
A Clinical Trial of MK-1045 in People With B-cell Acute Lymphoblastic Leukemia (MK-1045-005)
B-cell Acute Lymphoblastic Leukemia
RecruitingPhase 1
225Ac-DOTA-Anti-CD38 Daratumumab Monoclonal Antibody With Fludarabine, Melphalan and Total Marrow and Lymphoid Irradiation as Conditioning Treatment for Donor Stem Cell Transplant in Patients With High-Risk Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia and Myelodysplastic Syndrome
Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia
Recruiting
More Than Just X-Rays - Imaging of Chemotherapy-induced Morphological and Functional Cardiovascular and Lung Changes After Childhood ALL and Other Cancers - a Monocentric Late Effects Study (MaximALL)
Acute Lymphatic Leukemia, Lymphoma
RecruitingPhase 2
Sonrotoclax, Rituximab, and Zanubrutinib in Treating Participants With Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, and Mantle Cell Lymphoma
Chronic Lymphocytic Leukemia, Mantle Cell Lymphoma
RecruitingPhase 1/2
Phase I/II Trial: Engineered Donor Graft (Orca Q) for Pediatric Hematopoietic Cell Transplant (HCT)
Acute Myeloid Leukemia, Acute Lymphoid 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.
Kenneth Meehan, MD principal investigator
Dartmouth-Hitchcock Medical Center
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 Fludarabine, Busulfan and Rabbit ATG in people with Leukemia, Lymphoid and Leukemia, Myeloid, run by Dartmouth-Hitchcock 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 21 inclusion and 16 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 18 Oct 2023. 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?
Number of patients who are surviving at 100-Days post-transplant (time frame: 100 Days). 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 18 Oct 2023.