Trials / Completed
CompletedNCT03128359
High Dose Cyclophosphamide, Tacrolimus, and Mycophenolate Mofetil in Preventing Graft Versus Host Disease in Patients With Hematological Malignancies Undergoing Myeloablative or Reduced Intensity Donor Stem Cell Transplant
A Pilot Study of Post-transplant High Dose Cyclophosphamide (PTCY) as Part of Graft-Versus-Host Disease (GVHD) Prophylaxis in T-Cell Replete HLA-Mismatched Unrelated Donor (MMUD) Ablative and Reduced Intensity Hematopoietic Cell Transplantation (HCT) for Hematological Malignancies
- Status
- Completed
- Phase
- Phase 2
- Study type
- Interventional
- Enrollment
- 38 (actual)
- Sponsor
- City of Hope Medical Center · Academic / Other
- Sex
- All
- Age
- 5 Years – 75 Years
- Healthy volunteers
- Not accepted
Summary
This pilot phase II trial studies how well high dose cyclophosphamide, tacrolimus, and mycophenolate mofetil work in preventing graft versus host disease in patients with hematological malignancies undergoing myeloablative or reduced intensity donor stem cell transplant. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells (called graft versus host disease). Giving high dose cyclophosphamide, tacrolimus, and mycophenolate mofetil after the transplant may stop this from happening.
Detailed description
PRIMARY OBJECTIVES: I. To estimate the graft versus host disease (GVHD)-free relapse/progression-free survival (GRFS) at one-year post hematopoietic cell transplantation (HCT) and to evaluate the clinical activity of post-transplant high dose cyclophosphamide (PTCy). SECONDARY OBJECTIVES: I. To summarize toxicities/complications/infections including type, frequency, severity, attribution, time course and duration through 100 days post-transplant. II. To estimate the cumulative incidence (CI) of acute and chronic GVHD. III. To characterize the time course of neutrophil and platelet recovery/engraftment. IV. To estimate overall survival (OS), progression-free survival (PFS), CI of relapse/progression and non-relapse mortality (NRM) at 100 days, 1 year and 2 years. V. To describe quality of life at 100 days, 6 months, 1 and 2 years. VI. To characterize immune cell reconstitution and T cell repertoire post high dose cyclophosphamide in mismatched donor HCT. VII. To characterize quality of life. OUTLINE: CONDITIONING REGIMEN: Patients are assigned to 1 of 3 conditioning regimens at the discretion of the attending physician and principal investigator. REGIMEN A (REDUCED INTENSITY CONDITIONING): Patients receive fludarabine phosphate intravenously (IV) over 60 minutes on days -7 to -3 and melphalan hydrochloride IV over 20 minutes on day -2. REGIMEN B (MYELOABLATIVE CONDITIONING \[MAC\]): Patients receive fludarabine phosphate IV over 1-3 hours and busulfan IV over 3 hour on days -5 to -2. REGIMEN C (MAC): Patients receive fludarabine phosphate IV over 60 minutes on days -7 to -5 and total body irradiation (TBI) twice daily (BID) on days -4 to -1. TRANSPLANT: Patients undergo peripheral blood stem cell (PBSC) hematopoietic cell transplantation (HCT) on day 0. GVHD PROPHYLAXIS: Patients receive cyclophosphamide IV over 1-2 hours on days 3-4, mycophenolate mofetil IV or orally (PO) thrice daily (TID) beginning on day 5 and stopping on day 35 if no severe GVHD is present, and tacrolimus IV continuously on days 5-180 with a taper beginning on day 90 in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up twice weekly for 100 days, twice monthly for 6 months, monthly until no evidence of GVHD, and then yearly for up to 2 years.
Conditions
- Acute Leukemia
- Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
- Chronic Myelogenous Leukemia, BCR-ABL1 Positive
- Diffuse Large B-Cell Lymphoma
- Follicular Lymphoma
- Graft Versus Host Disease
- Hodgkin Lymphoma
- Mantle Cell Lymphoma
- Marginal Zone Lymphoma
- Myelodysplastic Syndrome
- Myeloproliferative Neoplasm
- Recurrent Acute Myeloid Leukemia With Myelodysplasia-Related Changes
- Recurrent Plasma Cell Myeloma
- Refractory Plasma Cell Myeloma
- Secondary Myelodysplastic Syndrome
Interventions
| Type | Name | Description |
|---|---|---|
| DRUG | Busulfan | Given IV |
| DRUG | Cyclophosphamide | Given IV |
| DRUG | Fludarabine Phosphate | Given IV |
| PROCEDURE | Hematopoietic Cell Transplantation | Undergo PBSC HCT |
| OTHER | Laboratory Biomarker Analysis | Correlative studies |
| DRUG | Melphalan Hydrochloride | Given IV |
| DRUG | Mycophenolate Mofetil | Given IV or PO |
| PROCEDURE | Peripheral Blood Stem Cell Transplantation | Undergo PBSC HCT |
| OTHER | Quality-of-Life Assessment | Ancillary studies |
| DRUG | Tacrolimus | Given IV |
| RADIATION | Total-Body Irradiation | Undergo TBI |
Timeline
- Start date
- 2017-05-30
- Primary completion
- 2020-08-01
- Completion
- 2021-09-15
- First posted
- 2017-04-25
- Last updated
- 2024-01-09
- Results posted
- 2023-06-09
Locations
1 site across 1 country: United States
Regulatory
- FDA-regulated drug study
Source: ClinicalTrials.gov record NCT03128359. Inclusion in this directory is not an endorsement.