Vedolizumab with post-transplant cyclophosphamide and short-course tacrolimus to prevent graft-versus-host disease after reduced-intensity allogeneic stem cell transplant
Phase-2 Study of Vedolizumab Plus Post-Transplant Cyclophosphamide and Short Course Tacrolimus for Graft-versus-Host Disease Prevention After Reduced Intensity Conditioning Peripheral Blood Stem Cell Allogeneic Hematopoietic Cell Transplantation
PHASE2 · City of Hope Medical Center · NCT06815003
This trial tests whether adding vedolizumab to post-transplant cyclophosphamide and a short course of tacrolimus can prevent graft-versus-host disease in adults getting reduced-intensity allogeneic stem cell transplants for leukemias or related blood disorders.
Quick facts
| Phase | PHASE2 |
|---|---|
| Study type | Interventional |
| Enrollment | 35 (estimated) |
| Ages | 18 Years to 80 Years |
| Sex | All |
| Sponsor | City of Hope Medical Center (other) |
| Drugs / interventions | Chemotherapy, immunotherapy, radiation, vedolizumab, cyclophosphamide, fludarabine |
| Locations | 1 site (Duarte, California) |
| Trial ID | NCT06815003 on ClinicalTrials.gov |
What this trial studies
This Phase II trial adds vedolizumab to a standard post-transplant cyclophosphamide (PTCy) and short-course tacrolimus regimen for patients receiving mobilized peripheral blood stem cell allogeneic transplants after reduced-intensity conditioning from an 8/8 matched related or unrelated donor. The study begins with a safety lead-in to describe toxicity of the fixed vedolizumab dose combined with PTCy and tacrolimus, then expands to assess efficacy by measuring grade 2-4 acute GVHD-free survival at day +180. Secondary outcomes include overall and progression-free survival, relapse and non-relapse mortality, rates of acute and chronic GVHD including lower GI involvement, infections, neutrophil recovery, and cytokine release syndrome frequency and severity.
Who should consider this trial
Good fit: Adults aged 18–80 with AML, ALL, MDS, or related disorders in appropriate remission who are eligible for reduced-intensity allogeneic HCT from an 8/8 matched related or unrelated donor and meet performance/comorbidity criteria (e.g., Karnofsky ≥70%).
Not a fit: Patients with uncontrolled active disease, mismatched or haploidentical donors, myelofibrosis, poor performance status, or who are otherwise ineligible for reduced-intensity PBSC allogeneic transplant are unlikely to benefit from this protocol.
Why it matters
Potential benefit: If successful, this approach could reduce the incidence of acute GVHD after reduced-intensity allogeneic HCT and improve transplant outcomes and quality of life for recipients.
How similar studies have performed: Post-transplant cyclophosphamide is an established GVHD prophylaxis approach and vedolizumab has shown benefit treating lower GI GVHD, but using vedolizumab upfront as prophylaxis with PTCy is relatively novel with limited prior data.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: * Documented informed consent of the participant and/or legally authorized representative * Assent, when appropriate, will be obtained per institutional guidelines * Agreement to allow the use of archival tissue from diagnostic tumor biopsies * If unavailable, exceptions may be granted with study principal investigator (PI) approval * Age: ≥ 18 and ≤ 80 years old * Note: Patients \> 70 years of age must have Karnofsky performance status ≥ 80 and hematopoietic cell transplantation-comorbidity index (HCT-CI) ≤ 2 * Karnofsky performance status ≥ 70% * Patients with the following diagnosis, eligible to undergo allogeneic HCT from an 8/8 match related/unrelated donor (A, B, C, DR by high resolution typing) * Acute Leukemias (acute myeloid leukemia \[AML\] or acute lymphoblastic leukemia \[ALL\]) in complete remission with bone marrow (BM) blast of \< 5% * Myelodysplastic syndrome (blast \< 10%) * Myeloproliferative neoplasm (MPN) other than myelofibrosis (MF) needing HCT * Chronic myelomonocytic leukemia (CMML) * Hemoglobin ≥ 9g/dL (within 30 days prior to day 1 of protocol therapy) * NOTE: Red blood cell transfusions are not permitted within 14 days of hemoglobin assessment unless cytopenia is secondary to disease involvement * Total bilirubin ≤ 2.0 mg/dL (unless has Gilbert's disease) AND serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT) \< 5 times the upper limit of normal (ULN) (within 30 days prior to day 1 of protocol therapy) * Aspartate aminotransferase (AST) =\< 3.0 x ULN (within 30 days prior to day 1 of protocol therapy) * Alanine aminotransferase (ALT) =\< 3.0 x ULN (within 30 days prior to day 1 of protocol therapy) * Creatinine clearance of ≤ 1.5 mg/dL or ≥ 60 mL/min per 24 hour urine test or the Cockcroft-Gault formula (within 30 days prior to day 1 of protocol therapy) * Left ventricular ejection fraction (LVEF) ≥ 50% * Note: To be performed within 28 days prior to day 1 of protocol therapy * IF ABLE TO PERFORM PULMONARY FUNCTION TESTS: Forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC) and DLCO (diffusion capacity) ≥ 50% of predicted (corrected for hemoglobin) * Note To be performed within 28 days prior to day 1 of protocol therapy * IF UNABLE TO PERFORM PULMONARY FUNCTION TESTS: Oxygen (O2) saturation \> 92% on room air * Note To be performed within 28 days prior to day 1 of protocol therapy * Seronegative for HIV antigen/antibody (Ag/Ab) combo, hepatitis C virus (HCV), active hepatitis B virus (HBV) (surface antigen negative) (within 30 days prior to day 1 of protocol therapy) * HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial * Tuberculosis test (within 30 days prior to day 1 of protocol therapy) * Patients with positive tuberculosis (TB) test results will have infectious disease (ID) evaluation and post HCT therapy with isoniazid (INH) for 6 months with ID follow up. Vaccinated patients will need negative chest X-ray results * Meets other institutional and federal requirements for infectious disease titer requirements * Note Infectious disease testing to be performed within 28 days prior to day 1 of protocol therapy * Women of childbearing potential (WOCBP): Negative urine or serum pregnancy test (within 30 days prior to day 1 of protocol therapy) * If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required * Agreement by females and males of childbearing potential to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least 3 months after the last dose of protocol therapy * Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for \> 1 year (women only) Exclusion Criteria: * Prior allogeneic HCT * Chemotherapy, radiation therapy, biological therapy, immunotherapy within 14 days prior to day 1 of protocol therapy * Note: Conditioning regimen within 14 days prior to day 1 of protocol therapy is not considered as an exclusion criterion. Patients on maintenance chemotherapy with agents listed are not excluded * Other investigational drugs for GVHD prophylaxis * Herbal medications * History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent * Clinically significant uncontrolled illness * Active infection not responding to antibiotics * Other active malignancy. Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial * Females only: Pregnant or breastfeeding * Patients not expected to be available for follow-up in our institution for at least 100 days after the transplant * Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures * Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)
Where this trial is running
Duarte, California
- City of Hope Medical Center — Duarte, California, United States (RECRUITING)
Study contacts
- Principal investigator: Monzr M. Al Malki — City of Hope Medical Center
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
Conditions: Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia, Chronic Myelomonocytic Leukemia, Graft Versus Host Disease, Myelodysplastic Syndrome, Myeloproliferative Neoplasm