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Acute Lymphoblastic LeukemiaPhase 1NCT02996773

Haploidentical BMT With Post-Transplant Cyclophosphamide and Bendamustine

A Phase 1 study testing Bendamustine and Cyclophosphamide in people with Acute Lymphoblastic Leukemia and Acute Myelogenous Leukemia, run by University of Arizona at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The purpose of this study is to evaluate the safety of progressively substituting day +3 and +4 post-transplant cyclophosphamide (PT-CY) with post-transplant bendamustine (PT-BEN) in myeloablative (MAC) haploidentical hematopoietic cell transplantation (HHCT) for patients with hematological malignancies. Read more about this study

Who is it for?
Ages 4 to 30 years
What is being tested?
Bendamustine and Cyclophosphamide
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
50 participants
Where
1 siteUnited States
Study dates
29 Nov 2016to 1 Aug 2025
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 4 to 30 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • Be willing and able to provide written consent/assent for the trial.
  • Diagnosed with one of the following high-risk malignancies, which require hematopoietic cell transplantation (HCT) but do not have an available Human Leukocyte Antigen (HLA)-matched related or unrelated donor or acceptable cord blood
  • High risk acute lymphoblastic leukemia (ALL) in 1st complete remission (CR1) or greater
  • High risk acute myelogenous leukemia (AML) in CR1 or greater
  • High risk undifferentiated acute leukemia
  • High risk myelodysplastic syndrome (MDS)
Show all 12Show fewer
  • Chronic Myelogenous Leukemia (CML) failing or intolerant to Tyrosine Kinase Inhibitors (TKIs) or in accelerated, blastic phase, or in second or subsequent chronic phase
  • Lymphoma, (Hodgkin and Non-Hodgkins Lymphoma including marginal zone, follicular lymphoma, chemotherapy-sensitive large-cell, mantle cell lymphoma, gray zone, and Burkitt's lymphoma in remission).
  • At least one haploidentical related donor is available for bone marrow harvest.
  • Molecular based HLA typing for the HLA-A, -B, -Cw, beta chain (-DRB1) and - DQ Beta 1 Locus (DQB1loci) to the resolution is needed to establish haploidentity.
  • A minimum match of 5/10 is required.
  • No availability of an 8/8 HLA-matched related or unrelated donor or clinical urgency for transplant (e.g., needed within 4-8 weeks) at which time an acceptable unrelated donor will not be available.

Who cannot join

  • Refractory acute leukemia (>5% blasts) or progressive disease
  • Untreated or progressive central nervous system leukemia
  • Refractory to chemotherapy lymphoma
  • Co-morbidities precluding patient's ability to tolerate BMT
  • Aspartate Aminotransferase (AST)/ Alanine Aminotransferase (ALT) > 5 x upper limit of normal (ULN)
  • Bilirubin > 2 x ULN
Show all 16Show fewer
  • Creatinine greater than >2 x ULN for age or creatinine clearance/glomerular filtration rate (GFR) <40 ml/min/1.73m2
  • Pulmonary function: Diffusing capacity of the lung for carbon monoxide (DLCO) < 40% of normal or O2 Sat <92%
  • Cardiac: left ventricular ejection fraction <35%
  • Active infection at time of hospital admission of Haplo BMT
  • Documented fungal infection or highly suspected and receiving treatment for presumed fungal infection within 3 months of BMT
  • HIV positive
  • Karnofsky score (adults) < 60% or Lansky score < 50% (pediatrics).
  • Positive pregnancy test for girls post menarche or women of childbearing age.
  • Severe psychiatric illness or mental deficiency making compliance to treatment unlikely and/or informed consent impossible.
  • Any reason, at the investigator's discretion, that the participation of the patient in this protocol would not be in patient's best interest, or where the patient would be unable to adhere to the study requirements.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • The University of Arizona Cancer Center

    Tucson, Arizona, 85724

Other trials in United States

About this study

Official title: A Phase I/Ib Study of Haploidentical Bone Marrow Transplant With Post-Transplant Cyclophosphamide and/or Bendamustine

The purpose of this study is to evaluate the safety of progressively substituting day +3 and +4 post-transplant cyclophosphamide (PT-CY) with post-transplant bendamustine (PT-BEN) in myeloablative (MAC) haploidentical hematopoietic cell transplantation (HHCT) for patients with hematological malignancies.

The goal of the Phase 1 component of the study is to evaluate the safety of progressively substituting post-transplant cyclophosphamide (PT-CY) given on Days +3 and +4 with bendamustine (PT-BEN). The Phase I component of the study has been completed.

Read more

The Phase Ib component of the study will continue to evaluate the safety and efficacy of subjects who receive PT-BEN on Days +3 and +4 at the maximum tolerated dose determined by Phase I. The Phase Ib component of the study has been completed.

Approximately, 18-36 subjects will be treated as part of Phase I and 15 as part of Phase Ib. Approximately 18 subjects will be used as controls, subjects that receive no PET-BEN, for direct comparison. Total, approximately 38-56 treatment and control patients and 38-56 donor subjects will be enrolled.

Read the detailed description

This study will follow the standard-of-care bone marrow transplant (BMT), with the only exception being to progressively substitute post-transplant cyclophosphamide (on Days +3 and +4 after BMT) with bendamustine. Six dose levels were planned for the Phase I component of the study, consisting of a combination of sequentially reduced doses of cyclophosphamide (PT-CY) and increased doses of bendamustine (PT-BEN) initially on Day +4 after BMT, followed by the same sequential reduction and increase on Day +3. An interim analysis was performed after cohort 3 was completed in Phase I and included a preliminary comparison between treatment and control groups. Phase Ib will evaluate patients treated with PT-CY on day +3 and PT-BEN on day +4.

Control patients will be patients that have declined to participate in the main trial but will receive haploidentical BMT with the current standard of two days of PT-CY (and no PT-BEN) and will be consented for the immune monitoring studies only.

Keywords
high-risk malignancies, Lymphoma, Haploidentical, Bone Marrow Transplant (BMT), Post-transplant, myeloablative (MAC), reduced intensity conditioning (RIC), haploidentical hematopoietic cell transplantation (HHCT), Leukemia
Medical subject headings
Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Myeloid, Acute, Myelodysplastic Syndromes, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Lymphoma, Non-Hodgkin, Hodgkin Disease, Lymphoma, Follicular, Lymphoma, B-Cell, Marginal Zone

What participants receive

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

  • BendamustineDrug

    Also called BEN

    After transplant, given intravenously on day +4 as part of Phase Ib.

  • CyclophosphamideDrug

    Also called CY

    After transplant, given intravenously on day +3 as part of Phase 1b.

Study groups in NCT02996773
Study groupRoleWhat they receive
Cyclophosphamide and BendamustineExperimentalExperimental: Cyclophosphamide and Bendamustine Control: Cyclophosphamide Interventions: * Drug: Bendamustine * Drug: Cyclophosphamide
Receives: Drug: Bendamustine; Drug: Cyclophosphamide

What is being measured

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

  1. Safety in regards to engraftment, incidence and grade of acute and chronic graft-versus-host-disease, graft failure, infections, relapse, and non-relapse mortality post-haploidentical bone marrow transplantation.

    Examine the effects of PT-BEN on immune reconstitution following human haploidentical BMT.

    Measured: Change from baseline to 3 years. Interim analysis will be performed after cohort 3 and cohort 6 in Phase 1, and include preliminary evaluation of treatment and control groups

Secondary outcomes (11)

  1. Incidence of regimen-related organ toxicities

    Measured: Change from baseline to 3 years. Interim analysis will be performed after cohort 3 and cohort 6 in Phase 1, and include preliminary evaluation of treatment and control groups]

  2. Incidence of acute GvHD

    Measured: Change from baseline to 3 years. Interim analysis will be performed after cohort 3 and cohort 6 in Phase 1, and include preliminary evaluation of treatment and control groups]

  3. Severity of acute GvHD

    Measured: Change from baseline to 3 years. Interim analysis will be performed after cohort 3 and cohort 6 in Phase 1, and include preliminary evaluation of treatment and control groups]

  4. Incidence of chronic GvHD

    Measured: Change from baseline to 3 years. Interim analysis will be performed after cohort 3 and cohort 6 in Phase 1, and include preliminary evaluation of treatment and control groups]

  5. Extent of chronic GvHD

    Measured: Change from baseline to 3 years. Interim analysis will be performed after cohort 3 and cohort 6 in Phase 1, and include preliminary evaluation of treatment and control groups]

  6. Incidence of graft failure

    Measured: Change from baseline to 3 years. Interim analysis will be performed after cohort 3 and cohort 6 in Phase 1, and include preliminary evaluation of treatment and control groups]

  7. Infection risk

    Immune reconstitution will be studied prospectively. Viral and fungal prophylaxis and treatment will be done according to our BMT programs guidelines

    Measured: Change from baseline to 3 years. Interim analysis will be performed after cohort 3 and cohort 6 in Phase 1, and include preliminary evaluation of treatment and control groups]

  8. Infection severity

    Immune reconstitution will be studied prospectively. Viral and fungal prophylaxis and treatment will be done according to our BMT programs guidelines

    Measured: Change from baseline to 3 years. Interim analysis will be performed after cohort 3 and cohort 6 in Phase 1, and include preliminary evaluation of treatment and control groups]

  9. Overall patient survival

    Measured: Change from baseline to 3 years. Interim analysis will be performed after cohort 3 and cohort 6 in Phase 1, and include preliminary evaluation of treatment and control groups]

  10. Immune reconstitution following haploidentical BMT

    T cell immune reconstitution (CD4, cluster of differentiation 8 (CD8), Treg, NK), B cell and myeloid cell reconstitution will be evaluated serially until 6 months post-BMT

    Measured: Change from baseline to 3 years. Interim analysis will be performed after cohort 3 and cohort 6 in Phase 1, and include preliminary evaluation of treatment and control groups]

  11. Incidence of bacterial, fungal and viral infections/reactivations

    Gather data on Incidence of bacterial, fungal and viral infections/reactivations

    Measured: Change from baseline to 3 years. Interim analysis will be performed after cohort 3 and cohort 6 in Phase 1, and include preliminary evaluation of treatment and control groups]

Timeline

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

  1. First posted19 Dec 2016 (estimated)
  2. Study start29 Nov 2016
  3. Primary completion1 Aug 2025
  4. Study completion1 Aug 2025

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
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
50 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02996773
Sponsor's protocol ID
1609876907
Status last verified
Nov 2025
First submitted
1 Dec 2016
Last updated
10 Nov 2025
Results posted
No
Data monitoring committee
Yes

Publications

  • Baker FL, Stokes J, Cracchiolo MJ, Davini D, Simpson RJ, Katsanis E. Impact of post-transplant cyclophosphamide with bendamustine on immune reconstitution in young patients undergoing T-cell replete haploidentical bone marrow transplantation: results from a phase Ia/Ib clinical trial. Front Immunol. 2025 Apr 9;16:1568862. doi: 10.3389/fimmu.2025.1568862. eCollection 2025.

    PubMed 40270968

  • Katsanis E, Stea B, Kovacs K, Truscott L, Husnain M, Khurana S, Roe DJ, Simpson RJ. Feasibility and Efficacy of Partially Replacing Post-Transplantation Cyclophosphamide with Bendamustine in Pediatric and Young Adult Patients Undergoing Haploidentical Bone Marrow Transplantation. Transplant Cell Ther. 2022 Jul;28(7):390.e1-390.e10. doi: 10.1016/j.jtct.2022.04.015. Epub 2022 Apr 20.

    PubMed 35460929

  • Katsanis E, Sapp LN, Reid SC, Reddivalla N, Stea B. T-Cell Replete Myeloablative Haploidentical Bone Marrow Transplantation Is an Effective Option for Pediatric and Young Adult Patients With High-Risk Hematologic Malignancies. Front Pediatr. 2020 Jun 9;8:282. doi: 10.3389/fped.2020.00282. eCollection 2020.

    PubMed 32582591

  • Katsanis E, Maher K, Roe DJ, Simpson RJ. Progressive substitution of posttransplant cyclophosphamide with bendamustine: A phase I study in haploidentical bone marrow transplantation. EJHaem. 2020 May 26;1(1):286-292. doi: 10.1002/jha2.20. eCollection 2020 Jul.

    PubMed 35847727

  • Katsanis E, Sapp LN, Varner N, Koza S, Stea B, Zeng Y. Haploidentical Bone Marrow Transplantation with Post-Transplant Cyclophosphamide/Bendamustine in Pediatric and Young Adult Patients with Hematologic Malignancies. Biol Blood Marrow Transplant. 2018 Oct;24(10):2034-2039. doi: 10.1016/j.bbmt.2018.06.007. Epub 2018 Jun 14.

    PubMed 29908231

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Bendamustine and Cyclophosphamide in people with Acute Lymphoblastic Leukemia and Acute Myelogenous Leukemia, run by University of Arizona 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 12 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 10 Nov 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?

Safety in regards to engraftment, incidence and grade of acute and chronic graft-versus-host-disease, graft failure, infections, relapse, and non-relapse mortality post-haploidentical bone marrow transplantation. (time frame: Change from baseline to 3 years. Interim analysis will be performed after cohort 3 and cohort 6 in Phase 1, and include preliminary evaluation of treatment and control groups). 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 NCT02996773, which also lists 5 linked publications.

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 10 Nov 2025.

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