This phase II trial studies pentostatin and donor lymphocyte infusion in preventing graft rejection in patients who have undergone donor stem cell transplant. Giving pentostatin and an infusion of the donor's T cells (donor lymphocyte infusion) after a donor stem cell transplant may stop the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving pentostatin before donor lymphocyte infusion may stop this from happening.
PRIMARY OBJECTIVES: I. To assess the safety and efficacy of the combined use of pentostatin and donor lymphocyte infusion (DLI) in patients with low or falling donor T-cell chimerism to prevent graft rejection after transplantation both from matched related donors (MRDs) or unrelated donors (URDs). SECONDARY OBJECTIVES: I. To determine the incidence of graft-versus-host disease (GvHD) infections and disease response, if persistent disease is present. OUTLINE: This is a dose-escalation study of donor lymphocyte infusion. GROUP I: Patients receive pentostatin intravenously (IV) over 20-30 minutes on day -2 and DLI over 15-30 minutes on day 0. Treatment may repeat once beginning with an escalated or same cluster of differentiation (CD)3-dose at least 4 weeks if persistent donor T-cells are documented, no GvHD has developed, and the chimerism status worsens or, if chimerism status is unchanged after at least 8 weeks with two subsequent tests of chimerism 4 weeks apart. GROUP II (initiated if patients in group I do not achieve sustained engraftment and improved chimerism): Patients receive treatment as in group I. Patients also receive cyclosporine orally (PO) twice daily (BID) on days -3 to 56 and mycophenolate mofetil PO once daily (QD) on days 0 to 27. Treatment continues in the absence of GvHD. After completion of study treatment, patients are followed up every 6 months for 2 years and then annually thereafter.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
36
Given PO
Given PO
Given IV
Given IV
Huntsman Cancer Institute/University of Utah
Salt Lake City, Utah, United States
LDS Hospital
Salt Lake City, Utah, United States
VA Puget Sound Health Care System
Seattle, Washington, United States
Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, United States
University of Torino
Torino, Italy
Percentage Patients With an Increase of at Least 10 Percentage Points in Donor T-cell Chimerism
A regimen will be considered successful if 20 patients are enrolled, at least 13 demonstrate improved chimerism. If fewer than 5 patients have shown improvement in chimerism then it can be at least 75% confident that the true rate of improvement is less than 0.53. Enrollment to the regimen will stop and the next regimen will be opened. Enrollment to a regimen may also be stopped at any time it becomes impossible to achieve 5 of 10 or 13 of 20 successful improvements. "Chimerism" in hematopoietic cell transplant derives from this idea of a "mixed" entity, referring to someone who has received a transplant of genetically different tissue. A test for chimerism after a hematopoietic cell transplant involves identifying the genetic profiles of the recipient and of the donor and then evaluating the extent of mixture in the recipient's blood cells or marrow cells.
Time frame: From the time of enrollment maintained to day 56 after the last DLI, up to Day 112
Incidence of Grade IV Acute GVHD
Clinical Stage of acute GVHD according to Organ System Skin: 1. \- Maculopapular rash \<25% of body surface 2. \- Maculopapular rash 25-50% of body surface 3. \- Maculopapular rash \>50% body surface area or generalized erythroderma 4. \- Generalized erythroderma with bullous formation and desquamation Liver: 1. \- Bilirubin 2-3 mg/dl 2. \- Bilirubin 3.1-6 mg/dl 3. \- Bilirubin 6.1-15 mg/dl 4. \- Bilirubin \>15 mg/dl Gut: 1. \- \>500-1000 mL diarrhea per day or (nausea, anorexia or vomiting with biopsy (EGD) confirmation of upper GI GVHD 2. \- \>1000 -1500 mL diarrhea per day 3. \- \>1500 mL diarrhea per day 4. \- \>1500 mL diarrhea per day plus severe abdominal pain with or without ileus Overall Clinical Grading of Severity of acute GVHD Grade IV: 0-4 Skin, 2-4 Liver, and/or 2-4 GI
Time frame: Within 100 days after the last DLI
Incidence of GVHD
Percentage patients with acute or chronic GVHD. The diagnosis of chronic GVHD requires at least one manifestation that is distinctive for chronic GVHD as opposed to acute GVHD. In all cases, infection and others causes must be ruled out in the differential diagnosis of chronic GVHD.
Time frame: 1 year after DLI
Incidence of Infections
Time frame: 100 days after DLI
Incidence of Relapse/Progression
CML Acquisition of a new cytogenetic abnormality and/or development of accelerated phase or blast crisis. Criteria for accelerated phase: unexplained fever \>38.3° C, new clonal cytogenetic abnormalities in addition to a single Ph-positive chromosome, BM blasts and promyelocytes \>20%. AML, ALL, CMML \>30% BM blasts w/ deteriorating performance status, or worsening of anemia, neutropenia, or thrombocytopenia. CLL Progressive disease: ≥1 of: physical exam/imaging studies (nodes, liver, and/or spleen) ≥50% increase or new, circulating lymphocytes by morphology and/or flow cytometry ≥50% increase, and lymph node biopsy w/ Richter's transformation. NHL \>25% increase in the sum of the products of the perpendicular diameters of marker lesions, or the appearance of new lesions. MM ≥100% increase of the serum myeloma protein from its lowest level, or reappearance of myeloma peaks that had disappeared w/ tx; or definite increase in the size/number of plasmacytomas or lytic bone lesions.
Time frame: 1 year after DLI
Survival
Percentage patients surviving.
Time frame: 1 year after DLI
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