Early Use of Tacrolimus in HLA-Mismatched Haploidentical Allogeneic Hematopoietic Transplantation With Post-Transplant Cyclophosphamide

NCT ID: NCT06828796

Last Updated: 2025-10-30

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

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

20 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-07-03

Study Completion Date

2028-06-30

Brief Summary

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To evalute the safety and efficacy in reducing Cytokine Release Syndrome after hematopoietic stem cell transplantation by introducing immunosuppression earlier in the transplant process

Detailed Description

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Conditions

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Hematologic Disease and Disorders Hematopoietic Cell Transplant

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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Tacrolimus + MMF + Post-Transplant Cyclophosphamide

Cyclophosphamide 50mg/kg/d Days +3 and +4 after transplant Tacrolimus Day -1 to Day +90 or Day +180 after transplant MMF 15mg/kg PO TID Day 0 to Day +35

Group Type EXPERIMENTAL

Tacrolimus

Intervention Type DRUG

Begins Day -1 and continues to Day +90 or Day +180 after transplant

Cyclophosphamide

Intervention Type DRUG

Given Days +3 and +4 after transplant

Mycofenolate mofetil

Intervention Type DRUG

Given Day 0 to Day +35 after transplant

Interventions

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Tacrolimus

Begins Day -1 and continues to Day +90 or Day +180 after transplant

Intervention Type DRUG

Cyclophosphamide

Given Days +3 and +4 after transplant

Intervention Type DRUG

Mycofenolate mofetil

Given Day 0 to Day +35 after transplant

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Availability of a 5/10-8/10 mismatched (HLA-A, B, DR) haploidentical related donor with a negative HLA cross-match in the host vs. graft direction and willing to provide peripheral blood stem cells
* Karnofsky status \>/= 70%
* Hematologic malignancy requiring allogeneic transplantation
* First allogeneic transplant only. Prior autologous transplant is allowed.

Exclusion Criteria

* Poor cardiac function: LVEF \<40%
* Poor pulmonary function: FEV1 and FVC \<50% predicted
* Poor liver function: bilirubin \>/= 3mg/dL (not due to hemolysis, Gilbert's or primary malignancy)
* Poor renal function: Creatinine \>/= 2mg/dL or creatinine clearance (calculated or measured creatinine clearance is permitted) \<40mL/min based on Traditional Cockcroft-Gault formula
* Women of childbearing potential who currently are pregnant or who are not practicing adequate contraception
* Patients who have any debilitating medical or psychiatric illness that would preclude their giving informed consent or their receiving optimal treatment and follow up
Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Northside Hospital, Inc.

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Melhem Solh, MD

Role: PRINCIPAL_INVESTIGATOR

The Blood and Marrow Transplant Group of Georgia

Locations

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Northside Hospital

Atlanta, Georgia, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Melh Solh, MD

Role: CONTACT

404-255-1930

Caitlin Guzowski, MBA, MHA, CCRC

Role: CONTACT

404-851-8523

Facility Contacts

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Caitlin Guzowski, MBA, MHA, CCRC

Role: primary

404-851-8523

References

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Solh MM, Dickhaus E, Solomon SR, Morris LE, Zhang X, Holland HK, Bashey A. Fevers post infusion of T-cell replete hla mismatched haploidentical hematopoietic stem cells with post-transplant cyclophosphamide: risk factors and impact on transplant outcomes. Bone Marrow Transplant. 2019 Nov;54(11):1756-1763. doi: 10.1038/s41409-019-0522-4. Epub 2019 Apr 5.

Reference Type RESULT
PMID: 30953027 (View on PubMed)

Tang J, Jensen RR, Bryan B, Hoda D, Hunter BD. Reduced Cytokine Release Syndrome and Improved Outcomes with Earlier Immunosuppressive Therapy in Haploidentical Stem Cell Transplantation. Transplant Cell Ther. 2024 Apr;30(4):438.e1-438.e11. doi: 10.1016/j.jtct.2024.01.076. Epub 2024 Jan 26.

Reference Type RESULT
PMID: 38281591 (View on PubMed)

Abboud R, Wan F, Mariotti J, Arango M, Castagna L, Romee R, Hamadani M, Chhabra S. Cytokine release syndrome after haploidentical hematopoietic cell transplantation: an international multicenter analysis. Bone Marrow Transplant. 2021 Nov;56(11):2763-2770. doi: 10.1038/s41409-021-01403-w. Epub 2021 Jul 14.

Reference Type RESULT
PMID: 34262142 (View on PubMed)

Abboud R, Keller J, Slade M, DiPersio JF, Westervelt P, Rettig MP, Meier S, Fehniger TA, Abboud CN, Uy GL, Vij R, Trinkaus KM, Schroeder MA, Romee R. Severe Cytokine-Release Syndrome after T Cell-Replete Peripheral Blood Haploidentical Donor Transplantation Is Associated with Poor Survival and Anti-IL-6 Therapy Is Safe and Well Tolerated. Biol Blood Marrow Transplant. 2016 Oct;22(10):1851-1860. doi: 10.1016/j.bbmt.2016.06.010. Epub 2016 Jun 16.

Reference Type RESULT
PMID: 27318038 (View on PubMed)

Ruggeri A, Labopin M, Battipaglia G, Chiusolo P, Tischer J, Diez-Martin JL, Bruno B, Castagna L, Moiseev IS, Vitek A, Rovira M, Ciceri F, Bacigalupo A, Nagler A, Mohty M. Timing of Post-Transplantation Cyclophosphamide Administration in Haploidentical Transplantation: A Comparative Study on Behalf of the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation. Biol Blood Marrow Transplant. 2020 Oct;26(10):1915-1922. doi: 10.1016/j.bbmt.2020.06.026. Epub 2020 Jul 6.

Reference Type RESULT
PMID: 32645444 (View on PubMed)

Chiusolo P, Bug G, Olivieri A, Brune M, Mordini N, Alessandrino PE, Dominietto A, Raiola AM, Di Grazia C, Gualandi F, Van Lint MT, Ferrara F, Finizio O, Angelucci E, Bacigalupo A. A Modified Post-Transplant Cyclophosphamide Regimen, for Unmanipulated Haploidentical Marrow Transplantation, in Acute Myeloid Leukemia: A Multicenter Study. Biol Blood Marrow Transplant. 2018 Jun;24(6):1243-1249. doi: 10.1016/j.bbmt.2018.01.031. Epub 2018 Feb 5.

Reference Type RESULT
PMID: 29421292 (View on PubMed)

Bashey A, Zhang X, Sizemore CA, Manion K, Brown S, Holland HK, Morris LE, Solomon SR. T-cell-replete HLA-haploidentical hematopoietic transplantation for hematologic malignancies using post-transplantation cyclophosphamide results in outcomes equivalent to those of contemporaneous HLA-matched related and unrelated donor transplantation. J Clin Oncol. 2013 Apr 1;31(10):1310-6. doi: 10.1200/JCO.2012.44.3523. Epub 2013 Feb 19.

Reference Type RESULT
PMID: 23423745 (View on PubMed)

Mayumi H, Umesue M, Nomoto K. Cyclophosphamide-induced immunological tolerance: an overview. Immunobiology. 1996 Jul;195(2):129-39. doi: 10.1016/S0171-2985(96)80033-7.

Reference Type RESULT
PMID: 8877390 (View on PubMed)

Jones RJ, Barber JP, Vala MS, Collector MI, Kaufmann SH, Ludeman SM, Colvin OM, Hilton J. Assessment of aldehyde dehydrogenase in viable cells. Blood. 1995 May 15;85(10):2742-6.

Reference Type RESULT
PMID: 7742535 (View on PubMed)

Fuchs EJ. Haploidentical transplantation for hematologic malignancies: where do we stand? Hematology Am Soc Hematol Educ Program. 2012;2012:230-6. doi: 10.1182/asheducation-2012.1.230.

Reference Type RESULT
PMID: 23233586 (View on PubMed)

Other Identifiers

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NSH 1420

Identifier Type: -

Identifier Source: org_study_id

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