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Bone Marrow Transplant ComplicationsPhase 1/2NCT05895201

High-Dose Post-Transplant Cyclophosphamide, Bortezomib, and Sitagliptin for the Prevention of GVHD

A Phase 1/2 study testing Sitagliptin, Bortezomib and Cyclophosphamide in people with Bone Marrow Transplant Complications and Acute Myeloid Leukemia, run by Indiana University at 1 site in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
Search all trials

Trial summary

This is an open label Phase I-II study to determine the safe doses of bortezomib, sitagliptin, and PTCy (Phase I) with expansion into a phase II trial to determine efficacy in improving survival. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Sitagliptin, Bortezomib and Cyclophosphamide
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
1 siteUnited States
Study dates
Nov 2023to Dec 2025
Phase
Phase 1/2
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

  • Patients with any of the following hematologic malignancies:
  • Acute myeloid leukemia (AML) in first remission (CR1) if they have with intermediate or high-risk cytogenetic and/or molecular features, or patients in second or subsequent complete remission (CR2, CR3, etc.). Complete remission is defined as presence of <5% blasts in the bone marrow Version 09/30/2022 25 with no morphological evidence of leukemia. Patients in CR with incomplete count recovery may be included.
  • Acute lymphoblastic leukemia (ALL) with any of the following in CR1 or subsequent complete remission (CR2, CR3, etc.). Complete remission is defined as presence of <5% blasts in the bone marrow with no morphological evidence of leukemia. Patients in CR with incomplete count recovery may be included.
  • Myelodysplastic disorder (MDS) with a revised International Prognostic System Score (IPSS-R)104 of greater than 3 at diagnosis. Patients must have <10% blasts in the bone marrow documented within 30 days of transplant.*
  • Therapy-related myelodysplastic disorder (t-MDS). Patients must have <10% blasts in the bone marrow documented within 30 days of transplant.*
  • Chronic myelomonocytic leukemia (CMML) type 1 or 2. Patients must have <10% blasts in the bone marrow documented within 30 days of transplant.* *Patients with MDS, t-MDS, and CMML will be included only in the phase I portion of the study.
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  • Patient age ≥ 18 years
  • Karnofsky Performance status ≥ 70%
  • Patients must also be suitable to receive a reduced-intensity (RIC) conditioning regimen at the discretion of the treating physician. While there are not universally accepted or validated cut-off criteria of age, performance status, or hematopoietic cell transplantation-comorbidity index (HCT-CI) for suitability for RIC, RIC transplants should be considered for patients 60 years and older, and for patients <60 years who are "less fit", e.g., KPS <90% and/or HCT-CI ≥ 3 due to lower non-relapse mortality associated with RIC.
  • Patients receiving allogeneic peripheral blood stem cell (PBSC) grafts from HLA-matched (5/6 and 6/6 matches) siblings or matched unrelated donors (7/8 or 8/8 matches at HLA-A, B, C, DRB1 by high resolution typing) are included. All grafts will be unmanipulated (i.e., no T cell depleted or CD34 selected grafts). In addition, donors should meet institutional criteria for donation of PBSC, as well as the screening and eligibility criteria of the National Marrow Donor Program (NMDP) for unrelated donors, and the requirements of the United States Food and Drug Administration for Human Cell, Tissue, or Cellular or Tissue-based Products (HCT/P) (21 CFR Part 1271).
  • Required baseline laboratory values within 16 days prior to admission:
  • Estimated creatinine clearance >60 ml/min/1.72 m2
  • Serum total bilirubin ≤ 2 x upper limit of normal value (except for Gilbert's disease)
  • AST and ALT ≤ 3 x upper limit of normal value
  • Alkaline phosphatase (ALP) ≤ 250 IU/l
  • Required baseline values within 60 days prior to admission:
  • Left ventricular ejection fraction (LVEF) >40% Version 09/30/2022 26
  • Adjusted carbon monoxide diffusing capacity (DLCO) >50%
  • No evidence of HIV infection (Patients with immune dysfunction are at a significantly higher risk of infection from intensive immunosuppressive therapies.)
  • Non-pregnant and non-nursing
  • Signed written informed consent
  • Patients must otherwise fulfill institutional criteria for eligibility to undergo reduced-intensity allogeneic stem cell transplantation.

Who cannot join

  • Pregnant or nursing females or women of reproductive capability who are unwilling to completely abstain from heterosexual sex or practice 2 effective methods of contraception from start of conditioning through a minimum of 90 days after the last dose of study drug.
  • Male subjects who refuse to practice effective barrier contraception from the start of conditioning through a minimum of 90 days after the last dose of study drug, or completely abstain from heterosexual intercourse.
  • Inability to provide informed consent.
  • Patient had myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities.
  • Patients with active central nervous system leukemia
  • Prior allogeneic HSCT or an autologous hematopoietic stem cell transplant in past 12 months
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  • Patients with diabetes mellitus requiring insulin secretagogues and/or insulin at time of enrollment.
  • Patients with a history of pancreatitis
  • Patients with symptomatic cholelithiasis
  • Known hypersensitivity to any of the components of the investigational treatment regimen.
  • Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
  • Diagnosed or treated for another malignancy within 3 years of enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma, an in-situ malignancy, or low-risk prostate cancer after curative therapy.
  • Participation in clinical trials with other investigational agents not included in this trial, within 14 days of the start of this trial and throughout the duration of this trial.
  • Prisoners

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Indiana University Melvin and Bren Simon Comprehensive Cancer Center

    Indianapolis, Indiana, 46202

Other trials in United States

About this study

Official title: Phase I/II Trial of High-Dose Post-Transplant Cyclophosphamide, Bortezomib, and Sitagliptin for the Prevention of Graft-versus-Host Disease Following Allogeneic Hematopoietic Stem Cell Transplantation

This is an open label Phase I-II study to determine the safe doses of bortezomib, sitagliptin, and PTCy (Phase I) with expansion into a phase II trial to determine efficacy in improving survival.

Read the detailed description

Determine the safe doses of bortezomib, sitagliptin, and PTCy for use in expansion into a phase II trial. This is effectively the maximum tolerated dose of the drugs tested in a 3+3 design in a limited phase I portion. Phase I requires a maximum of 18 patients.

Determine the efficacy of sitagliptin, bortezomib, and PTCy in improving the survival free of grade II-IV acute GVHD at day +100 from an expected 65% to 80% or more. This portion uses a Simon minimax two-stage design, testing the null hypothesis H0: p0 < 0.65 versus the alternative hypothesis H1: p1 ≥ 0.8, where p is the probability of being alive and without grade II-IV acute GVHD at day 100 after transplantation. Using a minimax optimal stage design with a one-sided type I error set to 0.05, and a type II error rate set to 0.2 (power 80%). In the first stage, 31 evaluable patients will be entered. If 20 or fewer are alive without acute grade II-IV GVHD (i.e., 11 or more develop acute grade II-IV GvHD) by day +100, the study will be stopped in favor of the null hypothesis. On the other hand, if more than 20 are alive without grade II-IV acute GVHD by day +100, and additional 24 patients will be enrolled for a total of 55 evaluable patients. In the final analysis, if more than 41 remain alive free of grade II-IV acute GVHD (i.e., only 14 or less have developed acute grade II-IV acute GVHD by day +100), the null hypothesis will be rejected, and will conclude that the combination used for prevention of moderate to severe GVHD is worthy of further study.

Keywords
Allogenic peripheral blood stem cell grafts, Phase I, Phase II
Medical subject headings
Leukemia, Myeloid, Acute, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Myelodysplastic Syndromes, Leukemia, Myelomonocytic, Chronic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • SitagliptinDrug

    600 or 400 (or MTD) mg PO every 12 hours on days -1 to +14 depending on dose level assignment.

  • BortezomibDrug

    1.3 or 1.0 mg/m2 (or MTD) IV push 6 hours after graft infusion completion (day 0), and 72 hours thereafter depending on dose level assignment.

  • CyclophosphamideDrug

    50 mg/kg IV over 1 hour on days +3 and +4

Study groups in NCT05895201
Study groupRoleWhat they receive
Sitagliptin + Bortezomib + CyclophosphamideExperimentalNot described
Receives: Drug: Sitagliptin; Drug: Bortezomib; Drug: Cyclophosphamide

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Maximum tolerated dose

    Measured: in the first 30 days post-transplant

  2. proportion of patients developing grades 3-4 non-hematological toxicity defining DLT assessed by CTCAE version 5.0

    Measured: in the first 30 days post-transplant

  3. Proportion of patients alive and free of grade II-IV acute GVHD (graft-versus-host disease)

    Measured: Baseline to day +100

  4. Cumulative incidence of grade II-IV acute GVHD

    Measured: through study completion (i.e. up to 5 years)

Secondary outcomes (13)

  1. Frequency of Non-Hematological toxicity as assessed by CTCAE version 5.0

    Measured: baseline to day +30

  2. Cumulative incidences of all grades of acute GvHD

    Measured: baseline to day +100

  3. Chronic graft-versus-host disease

    Measured: through study completion (i.e. up to 5 years)

  4. Time to engraftment of neutrophils

    Measured: the time from day 0 to the date of the first of three consecutive days after transplantation during which the absolute neutrophils count (NEUTROPHILS + BANDS) is at least 0.5 x109/l.

  5. Time to engraftment of platelets

    Measured: the time to engraftment of platelets is defined as the time from day 0 to the first of seven consecutive days after transplantation during which the platelet count is at least 20 x109/l without transfusion support.

  6. Cumulative Incidence engraftment of neutrophils and platelets

    Measured: day 0 to the first of seven consecutive days after transplantation during which the platelet count is ≥ 20 x109/l and ANC is ≥ 0.5 x109/l without transfusion.

  7. cumulative incidence of non-relapse mortality

    Measured: through study completion (i.e. up to 5 years)

  8. cumulative incidence of relapse

    Measured: through study completion (i.e. up to 5 years)

  9. Graft-versus-host free, and relapse-free survival (GRFS)

    Measured: Baseline to day+365

  10. chronic GvHD immunosuppression-free survival

    Measured: Baseline through day+365

  11. Grade III-IV acute GvHD-free survival

    Measured: baseline through day +180

  12. Progression-free Survival in all enrolled subjects

    Measured: Baseline through day+365

  13. Overall Survival in all enrolled subjects

    Measured: Baseline through day+365

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Jun 2023
  2. Study startNov 2023 (estimated)
  3. Primary completionDec 2025 (estimated)
  4. Study completionDec 2025 (estimated)

Why it stopped: PI has left IU with no plan to initiate study at IU

Resources

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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Sequential
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05895201
Sponsor's protocol ID
CTO-IUSCCC-0778
Status last verified
Oct 2023
First submitted
19 May 2023
Last updated
29 Apr 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Sitagliptin, Bortezomib and Cyclophosphamide in people with Bone Marrow Transplant Complications and Acute Myeloid Leukemia, run by Indiana University 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 22 inclusion and 14 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: withdrawn, as of the sponsor's last update on 29 Apr 2024. 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 combined 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.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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 was withdrawn before enrolling participants, so there are no results.

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?

Maximum tolerated dose (time frame: in the first 30 days post-transplant). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05895201.

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 29 Apr 2024.

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