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.
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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
SUPPORTIVE_CARE
Masking
NONE
Enrollment
38
Given IV
Given IV
Given IV
Undergo PBSC HCT
Correlative studies
Given IV
Given IV or PO
Undergo PBSC HCT
Ancillary studies
Given IV
Undergo TBI
City of Hope Medical Center
Duarte, California, United States
Graft-Versus-Host Disease-Free, Relapse-Free Survival (GRFS) at 1 Year
Estimates will be calculated using the Kaplan-Meier method, Greenwood formula will be used to calculate standard error (SE), and log-log transformation method will be used to construct 95% confidence intervals. Graft versus host disease (GVHD, acute and chronic), disease status and vital status will be monitored per clinical standard operating procedure. For this endpoint failure is defined as the first occurrence of grade 3 or 4 acute GVHD, or moderate/severe chronic GVHD, or disease relapse (for patients in complete remission at the start of conditioning) or disease progression (for patients with active disease at the start of conditioning) or death (from any cause). Patients not experiencing any of these will be censored at his/her date of last contact.
Time frame: From stem cell infusion to grade 3-4 acute graft versus host disease (GVHD), moderate-severe chronic GVHD, relapse, progression or death (from any cause), whichever occurs first, assessed for up to 1 year.
Acute Graft Versus Host Disease (aGVHD) of Grades 2-4 According to the Consensus Grading
Acute graft versus host disease is graded according to the 1994 Keystone Consensus Grading. aGVHD grade was evaluated from day 0 through 100 days post-transplant. The first day of acute GVHD onset at grades 2-4 was used to calculate the cumulative incidence. Relapse/death prior to onset was considered competing events.
Time frame: Up to 100 days post-stem cell infusion
Overall Survival (OS) at 1 Year
Estimates was calculated using the Kaplan-Meier method, Greenwood formula was used to calculate SE, and log-log transformation method was used to construct 95% confidence intervals. Each patient's vital status was monitored per clinical standard operating procedure. For this endpoint failure is defined as death (from any cause). Patients not experiencing a death event was censored at his/her date of last contact.
Time frame: From start of transplant to death, or last follow up, whichever occurs first, assessed for up to 1 year.
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