De-escalated Cyclophosphamide (PTCy) and Ruxolitinib for Graft-versus-Host Disease (GVHD) Prophylaxis

Sponsor

Medical College of Wisconsin (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05622318

Collaborator

(none)

Enrollment

Location

Arm

Anticipated Duration (Months)

1.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is an open-label phase 2 study designed to explore the efficacy and safety of low-dose PTCy-ruxolitinib GVHD prophylaxis in older adults undergoing allogeneic HCT with a matched sibling or unrelated donor with a peripheral blood stem cell graft.

Condition or Disease	Intervention/Treatment	Phase
Graft-versus-host Disease	Drug: Cyclophosphamide Drug: Tacrolimus Drug: Mycophenolate Mofetil Drug: Ruxolitinib	Phase 2

Detailed Description

Following reduced intensity conditioning and 8/8-matched peripheral blood transplant on Day 0, all patients will receive a GVHD prophylaxis post-transplant composed of the following: (i) cyclophosphamide administered at 25 mg/kg on Day +3 and +4, (ii) tacrolimus beginning on Day +5 and through Day +180 and administered with a trough target of 5-10 ng/ml through Day +90 and tapered thereafter; (iii) mycophenolate mofetil (MMF) administered at 15 mg/kg thrice daily beginning on Day +5 through Day +35; and (iv) ruxolitinib administered at 10 mg twice daily starting after engraftment (between Days +30 and +60) and continuing through one year post transplant.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

40 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Supportive Care

Official Title:

A Phase II Trial of De-escalated PTCy and Ruxolitinib for GVHD Prophylaxis in Patients Undergoing Reduced Intensity Conditioning Allogeneic HCT

Anticipated Study Start Date :

Apr 15, 2023

Anticipated Primary Completion Date :

Jul 15, 2025

Anticipated Study Completion Date :

Jul 15, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Graft-versus-host disease prophylaxis Following reduced intensity conditioning and 8/8-matched peripheral blood transplant on Day 0, all patients will receive a GVHD prophylaxis post-transplant composed of the following: (i) cyclophosphamide administered at 25 mg/kg on Day +3 and +4, (ii) tacrolimus beginning on Day +5 and through Day +180 and administered with a trough target of 5-10 ng/ml through Day +90 and tapered thereafter; (iii) mycophenolate mofetil (MMF) administered at 15 mg/kg thrice daily beginning on Day +5 through Day +35; and (iv) ruxolitinib administered at 10 mg twice daily starting after engraftment (between Days +30 and +60) and continuing through one year post transplant.	Drug: Cyclophosphamide 25 mg/kg by IV on Days +3 and +4. Other Names: Cytoxan Drug: Tacrolimus Target level 5-10 ng/mL (If the subject experiences nausea and vomiting that prevents the oral intake of tacrolimus anytime during treatment, tacrolimus is to be given by IV at the appropriate dose that was used to obtain the therapeutic level [IV:PO ratio = 1:4]). Administered Days +5 through +90. Taper after Day +90 and discontinue on Day +180. Other Names: Astagraf XL Envarsus XR Prograf Drug: Mycophenolate Mofetil 15 mg/kg tablet thrice daily Days +5 through +35 every eight hours. Other Names: CellCept Drug: Ruxolitinib 10 mg tablet twice daily after engraftment through Day +365. Taper after Day +365. Other Names: INC424 Jakafi

Arm

Intervention/Treatment

Experimental: Graft-versus-host disease prophylaxis

Drug: Cyclophosphamide

25 mg/kg by IV on Days +3 and +4.

Other Names:

Cytoxan

Drug: Tacrolimus

Target level 5-10 ng/mL (If the subject experiences nausea and vomiting that prevents the oral intake of tacrolimus anytime during treatment, tacrolimus is to be given by IV at the appropriate dose that was used to obtain the therapeutic level [IV:PO ratio = 1:4]). Administered Days +5 through +90. Taper after Day +90 and discontinue on Day +180.

Other Names:

Astagraf XL

Envarsus XR

Prograf

Drug: Mycophenolate Mofetil

15 mg/kg tablet thrice daily Days +5 through +35 every eight hours.

Other Names:

CellCept

Drug: Ruxolitinib

10 mg tablet twice daily after engraftment through Day +365. Taper after Day +365.

Other Names:

INC424

Jakafi

Outcome Measures

Primary Outcome Measures

The number of subjects who experience GVHD-free, relapse-free survival. [One year (365 Days) after hematopoietic cell transplantation (HCT)]
This measure is defined as being alive without having experiencing disease relapse, grade III/IV acute GVHD, or chronic GVHD requiring steroid treatment.

Secondary Outcome Measures

The number of subjects with acute GVHD at Day +100. [Day +100 after HCT]
The staging and grading of acute GVHD will be done according to Consensus GVHD grading criteria.
The number of subjects with acute GVHD at Day +180. [Day +180 after HCT]
The staging and grading of acute GVHD will be done according to Consensus GVHD grading criteria.
The number of subjects with chronic GVHD at one year. [One year after HCT]
Chronic GVHD will be graded as mild, moderate, or severe according to the NIH consensus criteria.
The number of subjects with non-relapse mortality at Day +100. [Day +100 after HCT]
This is defined as death before day +100 after transplant that was not preceded by recurrent or progressive malignancy.
The number of subjects with non-relapse mortality at one year. [One year after HCT]
This is defined as death before day +100 after transplant that was not preceded by recurrent or progressive malignancy.
Overall survival at one year. [One year after HCT]
This is defined as the number of subjects alive one year after HCT.

Eligibility Criteria

Criteria

Ages Eligible for Study:

60 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

History of hematologic malignancy.
Must be in remission:

Acute Leukemia, chronic leukemia, or myelodysplasia/myeloproliferative neoplasm (excluding primary myelofibrosis): No circulating blasts and <5% blasts in the bone marrow.
Hodgkin and non-Hodgkin lymphomas: Chemo-sensitive disease at time of transplant

Planned donor must be 8/8 human leukocyte antigen (HLA) -matched at HLA-A, -B, -DR, and -C.
Graft source of peripheral blood.
Planned reduced intensity conditioning therapy with fludarabine/melphalan, with total dose of melphalan of 100-140 mg/m^2 IV or fludarabine/busulfan with total dose of busulfan of 6.4 mg/kg IV.
Karnofsky Performance Scale of 60 or greater.
Male participants must agree to abstinence or to use of barrier contraception during the entire study period.
Female participants of childbearing potential will require a negative pregnancy test and should agree to practice two effective methods of contraception during the entire study period.
Ability to understand a written informed consent document, and the willingness to sign it.

Exclusion Criteria:

Prior allogeneic HCT or Chimeric antigen receptor (CAR) -T cell therapy.
Patients with liver dysfunction evidenced by bilirubin ≥2x upper limit normal (ULN), except for a history of Gilbert syndrome.
Patients with renal impairment defined by creatinine<2mg/dL.
Patients with cardiac dysfunction defined by a left ventricular ejection fraction ≤45%.
Patients with pulmonary dysfunction defined by a forced expiratory volume in the first second (FEV1) or diffusing capacity for carbon monoxide (DLCO) (corrected for hemoglobin) ≤50% of predicted.
Patients with a chronic or active infection requiring systemic treatment during and after transplant.
Presence of other active malignant disease diagnosed within 12 months, except for adequately treated non-melanoma skin cancer, adequately treated melanoma grade 2 or less, or cervical intraepithelial neoplasia. Active malignancy is malignancy receiving treatment.
Pregnant or lactating subjects.