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

NCT06828796 | Recruiting Phase 2 FDA Drug

• 1 other identifier: NSH 1420
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Hematologic Disease and Disorders; Hematopoietic Cell Transplant

Outcome Measures

Primary Outcomes (1)

• Efficacy in preventing CRS post transplant

  Evaluate the incidence of CRS during the first 5 days following stem cell transplant by recording signs and symptoms based on CTCAE v5.0.

  30 days

Secondary Outcomes (3)

• Severity of CRS after stem cell transplant

  30 days

• Safety of administering early immunosuppression

  6 months

• Safety of administering early immunosuppression

  1 year

Study Arms (1)

Tacrolimus + MMF + Post-Transplant Cyclophosphamide

EXPERIMENTAL

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

Drug: Tacrolimus; Drug: Cyclophosphamide; Drug: Mycofenolate mofetil

Interventions

Tacrolimus DRUG

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

Tacrolimus + MMF + Post-Transplant Cyclophosphamide

Cyclophosphamide DRUG

Given Days +3 and +4 after transplant

Tacrolimus + MMF + Post-Transplant Cyclophosphamide

Mycofenolate mofetil DRUG

Given Day 0 to Day +35 after transplant

Tacrolimus + MMF + Post-Transplant Cyclophosphamide

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Northside Hospital, Inc.: lead

Study Sites (1)

Northside Hospital

Atlanta, Georgia, 30342, United States

RECRUITING

Related Publications (10)

• 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.

  PMID: 30953027 RESULT

• 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.

  PMID: 38281591 RESULT

• 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.

  PMID: 34262142 RESULT

• 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.

  PMID: 27318038 RESULT

• 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.

  PMID: 32645444 RESULT

• 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.

  PMID: 29421292 RESULT

• 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.

  PMID: 23423745 RESULT

• 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.

  PMID: 8877390 RESULT

• 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.

  PMID: 7742535 RESULT

• 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.

  PMID: 23233586 RESULT

MeSH Terms

Conditions

Hematologic Diseases; Disease

Interventions

Tacrolimus; Cyclophosphamide

Condition Hierarchy (Ancestors)

Hemic and Lymphatic Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Phosphoramides; Organophosphorus Compounds

Study Officials

• Melhem Solh, MD

  The Blood and Marrow Transplant Group of Georgia

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Melh Solh, MD

CONTACT

404-255-1930; msolh@bmtga.com

Caitlin Guzowski, MBA, MHA, CCRC

CONTACT

404-851-8523; caitlin.guzowski@northside.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 6, 2025
• First Posted: February 14, 2025
• Study Start: July 3, 2025
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): June 30, 2028
• Last Updated: April 16, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR

Locations

US (1)