Haploidentical BMT With Post-Transplant Cyclophosphamide and Bendamustine

NCT ID: NCT02996773

Last Updated: 2025-11-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

50 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-11-29

Study Completion Date

2025-08-01

Brief Summary

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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.

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.

Detailed Description

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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.

Conditions

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Acute Lymphoblastic Leukemia Acute Myelogenous Leukemia Myelodysplastic Syndromes Chronic Myelogenous Leukemia Lymphoma,Non-Hodgkin Lymphoma, Hodgkin Lymphoma, Follicular Marginal Zone Lymphoma Large Cell Lymphoma Mantle-Cell Lymphoma Gray Zone Lymphoma Burkitt Lymphoma High Risk Undifferentiated Acute Leukemia

Keywords

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high-risk malignancies Lymphoma Haploidentical Bone Marrow Transplant (BMT) Post-transplant myeloablative (MAC) reduced intensity conditioning (RIC) haploidentical hematopoietic cell transplantation (HHCT) Leukemia

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Cyclophosphamide and Bendamustine

Experimental: Cyclophosphamide and Bendamustine Control: Cyclophosphamide

Interventions:

* Drug: Bendamustine
* Drug: Cyclophosphamide

Group Type EXPERIMENTAL

Bendamustine

Intervention Type DRUG

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

Cyclophosphamide

Intervention Type DRUG

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

Interventions

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Bendamustine

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

Intervention Type DRUG

Cyclophosphamide

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

Intervention Type DRUG

Other Intervention Names

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BEN CY

Eligibility Criteria

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Inclusion Criteria

* 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)
* 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.

Exclusion Criteria

* 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
* 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.
Minimum Eligible Age

4 Years

Maximum Eligible Age

30 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Arizona

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Emmanuel Katsanis, MD

Role: PRINCIPAL_INVESTIGATOR

The University of Arizona Cancer Center

Locations

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The University of Arizona Cancer Center

Tucson, Arizona, United States

Site Status

Countries

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United States

References

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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.

Reference Type RESULT
PMID: 40270968 (View on PubMed)

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.

Reference Type RESULT
PMID: 35460929 (View on PubMed)

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.

Reference Type RESULT
PMID: 32582591 (View on PubMed)

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.

Reference Type RESULT
PMID: 35847727 (View on PubMed)

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.

Reference Type RESULT
PMID: 29908231 (View on PubMed)

Other Identifiers

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1609876907

Identifier Type: -

Identifier Source: org_study_id