Haploidentical BMT With Post-Transplant Cyclophosphamide and Bendamustine

NCT02996773 | Completed Phase 1 DMC

• 1 other identifier: 1609876907
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

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

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

Outcome Measures

Primary Outcomes (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.

  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)

• Incidence of regimen-related organ toxicities

  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]

• Incidence of acute GvHD

  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]

• Severity of acute GvHD

  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]

• Incidence of chronic GvHD

  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]

• Extent of chronic GvHD

  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]

Study Arms (1)

Cyclophosphamide and Bendamustine

EXPERIMENTAL

Experimental: Cyclophosphamide and Bendamustine Control: Cyclophosphamide Interventions: * Drug: Bendamustine * Drug: Cyclophosphamide

Drug: Bendamustine; Drug: Cyclophosphamide

Interventions

Bendamustine DRUG

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

Also known as: BEN

Cyclophosphamide and Bendamustine

Cyclophosphamide DRUG

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

Also known as: CY

Cyclophosphamide and Bendamustine

Eligibility Criteria

• Age: 4 Years - 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Arizona: lead

Study Sites (1)

The University of Arizona Cancer Center

Tucson, Arizona, 85724, United States

Location

Related Publications (5)

• 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.

  PMID: 40270968 RESULT

• 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.

  PMID: 35460929 RESULT

• 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.

  PMID: 32582591 RESULT

• 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.

  PMID: 35847727 RESULT

• 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.

  PMID: 29908231 RESULT

MeSH Terms

Conditions

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; Dendritic Cell Sarcoma, Interdigitating; Lymphoma, Mantle-Cell; Burkitt Lymphoma; Lymphoma; Mycobacterium avium-intracellulare Infection; Leukemia

Interventions

Bendamustine Hydrochloride; Cyclophosphamide

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Myeloid; Bone Marrow Diseases; Myeloproliferative Disorders; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lymphoma, B-Cell; Histiocytic Disorders, Malignant; Histiocytosis; Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Mycobacterium Infections, Nontuberculous; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses

Intervention Hierarchy (Ancestors)

Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Phosphoramide Mustards; Phosphoramides; Organophosphorus Compounds

Study Officials

• Emmanuel Katsanis, MD

  The University of Arizona Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 1, 2016
• First Posted: December 19, 2016
• Study Start: November 29, 2016
• Primary Completion: August 1, 2025
• Study Completion: August 1, 2025
• Last Updated: November 10, 2025

Record last verified: 2025-11

Locations

US (1)