Pentostatin and Lymphocyte Infusion in Preventing Graft Rejection in Patients Who Have Undergone Donor Stem Cell Transplant

Condition(s): Accelerated Phase Chronic Myelogenous Leukemia Adult Acute Lymphoblastic Leukemia in Remission Adult Acute Myeloid Leukemia in Remission Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities Adult Acute Myeloid Leukemia With Del(5q) Adult Acute Myeloid Leukemia With Inv(16)(p13;q22) Adult Acute Myeloid Leukemia With t(15;17)(q22;q12) Adult Acute Myeloid Leukemia With t(16;16)(p13;q22) Adult Acute Myeloid Leukemia With T(8;21)(q22;q22) Atypical Chronic Myeloid Leukemia, BCR-ABL Negative Blastic Phase Chronic Myelogenous Leukemia Childhood Acute Lymphoblastic Leukemia in Remission Childhood Acute Myeloid Leukemia in Remission Childhood Chronic Myelogenous Leukemia Childhood Myelodysplastic Syndromes Chronic Eosinophilic Leukemia Chronic Myelomonocytic Leukemia Chronic Neutrophilic Leukemia Chronic Phase Chronic Myelogenous Leukemia De Novo Myelodysplastic Syndromes Disseminated Neuroblastoma Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue Juvenile Myelomonocytic Leukemia Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable Nodal Marginal Zone B-cell Lymphoma Noncontiguous Stage II Adult Burkitt Lymphoma Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma Noncontiguous Stage II Adult Diffuse Mixed Cell Lymphoma Noncontiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma Noncontiguous Stage II Adult Immunoblastic Large Cell Lymphoma Noncontiguous Stage II Adult Lymphoblastic Lymphoma Noncontiguous Stage II Grade 1 Follicular Lymphoma Noncontiguous Stage II Grade 2 Follicular Lymphoma Noncontiguous Stage II Grade 3 Follicular Lymphoma Noncontiguous Stage II Mantle Cell Lymphoma Noncontiguous Stage II Marginal Zone Lymphoma Noncontiguous Stage II Small Lymphocytic Lymphoma Poor Prognosis Metastatic Gestational Trophoblastic Tumor Previously Treated Childhood Rhabdomyosarcoma Previously Treated Myelodysplastic Syndromes Primary Myelofibrosis Secondary Acute Myeloid Leukemia Secondary Myelodysplastic Syndromes Splenic Marginal Zone Lymphoma Stage I Multiple Myeloma Stage II Multiple Myeloma Stage II Ovarian Epithelial Cancer Stage III Adult Burkitt Lymphoma Stage III Adult Diffuse Large Cell Lymphoma Stage III Adult Diffuse Mixed Cell Lymphoma Stage III Adult Diffuse Small Cleaved Cell Lymphoma Stage III Adult Hodgkin Lymphoma Stage III Adult Immunoblastic Large Cell Lymphoma Stage III Adult Lymphoblastic Lymphoma Stage III Chronic Lymphocytic Leukemia Stage III Grade 1 Follicular Lymphoma Stage III Grade 2 Follicular Lymphoma Stage III Grade 3 Follicular Lymphoma Stage III Malignant Testicular Germ Cell Tumor Stage III Mantle Cell Lymphoma Stage III Marginal Zone Lymphoma Stage III Multiple Myeloma Stage III Ovarian Epithelial Cancer Stage III Small Lymphocytic Lymphoma Stage IIIA Breast Cancer Stage IIIB Breast Cancer Stage IIIC Breast Cancer Stage IV Adult Burkitt Lymphoma Stage IV Adult Diffuse Large Cell Lymphoma Stage IV Adult Diffuse Mixed Cell Lymphoma Stage IV Adult Diffuse Small Cleaved Cell Lymphoma Stage IV Adult Hodgkin Lymphoma Stage IV Adult Immunoblastic Large Cell Lymphoma Stage IV Breast Cancer Stage IV Chronic Lymphocytic Leukemia Stage IV Grade 1 Follicular Lymphoma Stage IV Grade 2 Follicular Lymphoma Stage IV Grade 3 Follicular Lymphoma Stage IV Mantle Cell Lymphoma Stage IV Marginal Zone Lymphoma Stage IV Ovarian Epithelial Cancer Stage IV Small Lymphocytic Lymphoma Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative High Risk Metastatic Gestational Trophoblastic Tumor
NCTId: NCT00096161

Official Title

Pentostatin and Donor Lymphocyte Infusion for Low Donor T-Cell Chimerism After Hematopoietic Cell Transplantation - A Multi-Center Trial

Summary

This clinical 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.

Detailed Description

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. Patients are assigned to 1 of 2 treatment groups.

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.

Eligibility

Eligibility Criteria

Gender Minimum Age Maximum Age Healthy Volunteers?
Both N/A N/A False

Inclusion Criteria:

- Patients having received a preceding allogeneic transplantation from either a human leukocyte antigen (HLA)-matched related or unrelated donor are eligible for this protocol

- Related donor: HLA genotypically identical at least at one haplotype and may be phenotypically or genotypically identical at the allele level at HLA A, B, C, DRB1, and DQB1

- Unrelated donor who are prospectively:

- Matched for HLA-A, B, C, DRB1 and DQB1 by high resolution typing; OR

- Only a single allele disparity will be allowed for HLA-A, B, or C as defined by high resolution typing

- Patients with less than 50% donor CD3 peripheral blood chimerism on two separate, consecutive evaluations (the two evaluations must be at least 14 days apart) OR patients with absolute decreases of donor CD3 peripheral blood chimerism of >= 20% if the second test shows < 50% donor CD3 cells (the two evaluations must be at least 14 days apart)

- Patients with evidence of disease are only eligible if the disease is stable (or persistent) in comparison to the status prior to transplantation

- Patients must be tapered off systemic steroids to a dosage of less than or equal to 0.25 mg/kg/day

- Patients must have persistent donor CD3 cells (>= 5% donor CD3 cells by a deoxyribonucleic acid [DNA]-based assay that compares the profile of amplified fragment length polymorphisms [ampFLP] [or fluorescent in situ hybridization (FISH) studies or variable number of tandem repeats (VNTR)])

- DONOR: Alternatively to a fresh unmodified leukapheresis product, previously collected cryopreserved peripheral blood stem cells (PBSC) after mobilization with G-CSF or cryopreserved unmodified leukapheresis product from the original donor can be used; if cryopreserved product is not available, the following criteria apply for the DLI product:

- DONOR: Original donor of hematopoietic cell transplantation

- DONOR: Donor must give consent to leukapheresis

- DONOR: Donor must have adequate veins for leukapheresis or agree to placement of central venous catheter (femoral or subclavian)

- DONOR: Donor must be medically fit to undergo the apheresis procedure (institutional guidelines for apheresis)

Exclusion Criteria:

- Current grade II to IV acute GVHD or extensive chronic GVHD

- Karnofsky score < 50%

- Lansky Play-Performance Score < 40

- Evidence of relapse or progression of disease after transplantation

- Prior recipient of cord blood

- DONOR: Donor who are not suitable for medical reasons to donate peripheral blood mononuclear cells (PBMC) by continuous centrifugation according to the criteria of the American Association of Blood Banks (AABB)

- DONOR: Pregnancy

- DONOR: Human immunodeficiency virus (HIV) or human T-lymphotrophic virus (HTLV) infection

- DONOR: Recent immunization may require a delay

Interventions & Outcomes

Study Interventions & Types

Drug Intervention(s)

cyclosporine - Given orally
cyclosporine - Given PO
mycophenolate mofetil - Given orally
mycophenolate mofetil - Given PO
pentostatin - Given IV

Biological Intervention(s)

therapeutic allogeneic lymphocytes - Given IV

Study Outcomes

Primary Outcome(s)

Timeframe: From the time of enrollment maintained to day 56 after the last DLI
Measure: Efficacy of the combined use of pentostatin and DLI defined as an increase of at least 10 percentage points in donor T-cell chimerism
Description: 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 we 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.
Safety Issue? No

Timeframe: Within 100 days after the last DLI
Measure: Safety of the combined use of pentostatin and DLI as defined by an acceptable rate of grade IV acute GVHD
Description: Reported following the Fred Hutchinson Cancer Research Center (FHCRC) Guidelines for serious adverse event (SAE) reporting.
Safety Issue? Yes

Secondary Outcome(s)

Measure: Disease response of the combined use of pentostatin and DLI
Timeframe: Up to 12 years
Safety Issue? No

Measure: Incidence of chronic GVHD infection
Timeframe: 1 year
Description: Reported following the FHCRC Guidelines for SAE reporting.
Safety Issue? No

Measure: Incidence of chronic GVHD infection
Timeframe: Day 84
Description: Reported following the FHCRC Guidelines for SAE reporting.
Safety Issue? No

Measure: Incidence of grade II-IV acute GVHD infection
Timeframe: 1 year
Description: Reported following the FHCRC Guidelines for SAE reporting. Accrual to a regimen will stop at any time there is reasonable evidence that the rate of grade IV acute GVHD exceeds 0.15.
Safety Issue? No

Measure: Incidence of grade II-IV acute GVHD infection
Timeframe: Day 84
Description: Reported following the FHCRC Guidelines for SAE reporting. Accrual to a regimen will stop at any time there is reasonable evidence that the rate of grade IV acute GVHD exceeds 0.15.
Safety Issue? No

Measure: Relapse/progression
Timeframe: Up to 12 years
Safety Issue? No

Measure: Survival
Timeframe: Up to 12 years
Safety Issue? No

Facility Locations

Research Study Facility Map

Map of facility locations for this research study.

Facility is recruiting
Facility is not yet recruiting
Unknown status

Clinical Research Study Facility Locations

Recruiting

University of Torino
Torino, 10126 Italy

VA Puget Sound Health Care System
Seattle, Washington 98101 United States

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington 98109 United States

Completed

LDS Hospital
Salt Lake City, Utah 84143 United States

Huntsman Cancer Institute/University of Utah
Salt Lake City, Utah 84112 United States

Related Keywords & Studies

Conditions and Diseases with Related Research Studies

  1. Accelerated Phase Chronic Myelogenous Leukemia
  2. Adult Acute Lymphoblastic Leukemia in Remission
  3. Adult Acute Myeloid Leukemia in Remission
  4. Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities
  5. Adult Acute Myeloid Leukemia With Del(5q)
  6. Adult Acute Myeloid Leukemia With Inv(16)(p13;q22)
  7. Adult Acute Myeloid Leukemia With t(15;17)(q22;q12)
  8. Adult Acute Myeloid Leukemia With t(16;16)(p13;q22)
  9. Adult Acute Myeloid Leukemia With T(8;21)(q22;q22)
  10. Atypical Chronic Myeloid Leukemia, BCR-ABL Negative
  11. Blastic Phase Chronic Myelogenous Leukemia
  12. Childhood Acute Lymphoblastic Leukemia in Remission
  13. Childhood Acute Myeloid Leukemia in Remission
  14. Childhood Chronic Myelogenous Leukemia
  15. Childhood Myelodysplastic Syndromes
  16. Chronic Eosinophilic Leukemia
  17. Chronic Myelomonocytic Leukemia
  18. Chronic Neutrophilic Leukemia
  19. Chronic Phase Chronic Myelogenous Leukemia
  20. De Novo Myelodysplastic Syndromes
  21. Disseminated Neuroblastoma
  22. Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
  23. Juvenile Myelomonocytic Leukemia
  24. Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable
  25. Nodal Marginal Zone B-cell Lymphoma
  26. Noncontiguous Stage II Adult Burkitt Lymphoma
  27. Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma
  28. Noncontiguous Stage II Adult Diffuse Mixed Cell Lymphoma
  29. Noncontiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma
  30. Noncontiguous Stage II Adult Immunoblastic Large Cell Lymphoma
  31. Noncontiguous Stage II Adult Lymphoblastic Lymphoma
  32. Noncontiguous Stage II Grade 1 Follicular Lymphoma
  33. Noncontiguous Stage II Grade 2 Follicular Lymphoma
  34. Noncontiguous Stage II Grade 3 Follicular Lymphoma
  35. Noncontiguous Stage II Mantle Cell Lymphoma
  36. Noncontiguous Stage II Marginal Zone Lymphoma
  37. Noncontiguous Stage II Small Lymphocytic Lymphoma
  38. Poor Prognosis Metastatic Gestational Trophoblastic Tumor
  39. Previously Treated Childhood Rhabdomyosarcoma
  40. Previously Treated Myelodysplastic Syndromes
  41. Primary Myelofibrosis
  42. Secondary Acute Myeloid Leukemia
  43. Secondary Myelodysplastic Syndromes
  44. Splenic Marginal Zone Lymphoma
  45. Stage I Multiple Myeloma
  46. Stage II Multiple Myeloma
  47. Stage II Ovarian Epithelial Cancer
  48. Stage III Adult Burkitt Lymphoma
  49. Stage III Adult Diffuse Large Cell Lymphoma
  50. Stage III Adult Diffuse Mixed Cell Lymphoma
  51. Stage III Adult Diffuse Small Cleaved Cell Lymphoma
  52. Stage III Adult Hodgkin Lymphoma
  53. Stage III Adult Immunoblastic Large Cell Lymphoma
  54. Stage III Adult Lymphoblastic Lymphoma
  55. Stage III Chronic Lymphocytic Leukemia
  56. Stage III Grade 1 Follicular Lymphoma
  57. Stage III Grade 2 Follicular Lymphoma
  58. Stage III Grade 3 Follicular Lymphoma
  59. Stage III Malignant Testicular Germ Cell Tumor
  60. Stage III Mantle Cell Lymphoma
  61. Stage III Marginal Zone Lymphoma
  62. Stage III Multiple Myeloma
  63. Stage III Ovarian Epithelial Cancer
  64. Stage III Small Lymphocytic Lymphoma
  65. Stage IIIA Breast Cancer
  66. Stage IIIB Breast Cancer
  67. Stage IIIC Breast Cancer
  68. Stage IV Adult Burkitt Lymphoma
  69. Stage IV Adult Diffuse Large Cell Lymphoma
  70. Stage IV Adult Diffuse Mixed Cell Lymphoma
  71. Stage IV Adult Diffuse Small Cleaved Cell Lymphoma
  72. Stage IV Adult Hodgkin Lymphoma
  73. Stage IV Adult Immunoblastic Large Cell Lymphoma
  74. Stage IV Breast Cancer
  75. Stage IV Chronic Lymphocytic Leukemia
  76. Stage IV Grade 1 Follicular Lymphoma
  77. Stage IV Grade 2 Follicular Lymphoma
  78. Stage IV Grade 3 Follicular Lymphoma
  79. Stage IV Mantle Cell Lymphoma
  80. Stage IV Marginal Zone Lymphoma
  81. Stage IV Ovarian Epithelial Cancer
  82. Stage IV Small Lymphocytic Lymphoma
  83. Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative
  84. High Risk Metastatic Gestational Trophoblastic Tumor

Other Related Condition Keywords

  1. Congenital Abnormalities
  2. Blast Crisis
  3. Breast Neoplasms
  4. Burkitt Lymphoma
  5. Neoplasms
  6. Hodgkin Disease
  7. Leukemia
  8. Leukemia, Lymphocytic, Chronic, B-Cell
  9. Leukemia, Lymphoid
  10. Precursor Cell Lymphoblastic Leukemia-Lymphoma
  11. Leukemia, Myeloid, Acute
  12. Leukemia, Myeloid
  13. Leukemia, Myeloid, Accelerated Phase
  14. Leukemia, Myelogenous, Chronic, BCR-ABL Positive
  15. Leukemia, Myeloid, Chronic-Phase
  16. Leukemia, Myelomonocytic, Chronic
  17. Leukemia, Neutrophilic, Chronic
  18. Lymphoma
  19. Lymphoma, Follicular
  20. Lymphoma, Large B-Cell, Diffuse
  21. Lymphoma, Non-Hodgkin
  22. Multiple Myeloma
  23. Neoplasms, Plasma Cell
  24. Myelodysplastic Syndromes
  25. Preleukemia
  26. Leukemia, Myelomonocytic, Acute
  27. Myeloproliferative Disorders
  28. Neuroblastoma
  29. Rhabdomyosarcoma
  30. Testicular Neoplasms
  31. Trophoblastic Neoplasms
  32. Lymphoma, B-Cell
  33. Lymphoma, Large-Cell, Immunoblastic
  34. Neoplasms, Germ Cell and Embryonal
  35. Hypereosinophilic Syndrome
  36. Rhabdomyosarcoma, Embryonal
  37. Lymphoma, B-Cell, Marginal Zone
  38. Lymphoma, Mantle-Cell
  39. Leukemia, Myelomonocytic, Juvenile
  40. Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative
  41. Neoplasms, Glandular and Epithelial
  42. Ovarian Neoplasms
  43. Gestational Trophoblastic Neoplasms
  44. Myelodysplastic-Myeloproliferative Diseases

Related Intervention Keywords

Related Accelerated Phase Chronic Myelogenous Leukemia Research

  1. A Pilot Study to Evaluate the Co-Infusion of Ex Vivo Expanded Cord Blood Cells With an Unmanipulated Cord Blood Unit in Patients Undergoing Cord Blood Transplant for Hematologic Malignancies
  2. Computer-Guided Glucose Management Systems in Treating Patients With Hyperglycemia Who Have Undergone Blood and Bone Marrow Transplant
  3. Cyclophosphamide for Prevention of Graft-Versus-Host Disease After Allogeneic Peripheral Blood Stem Cell Transplantation in Patients With Hematological Malignancies
  4. Donor Atorvastatin Treatment for Preventing Severe Acute Graft-Versus-Host Disease in Patients Undergoing Myeloablative Peripheral Blood Stem Cell Transplantation
  5. Donor Lymphocyte Infusion in Treating Patients With Persistent, Relapsed, or Progressing Cancer After Donor Hematopoietic Cell Transplant
  6. Donor T Cells After Donor Stem Cell Transplant in Treating Patients With Hematologic Malignancies
  7. Donor Umbilical Cord Blood Transplant With or Without Ex-Vivo Expanded Cord Blood Progenitor Cells in Treating Patients With Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Chronic Myelogenous Leukemia, or Myelodysplastic Syndromes
  8. Fludarabine and Total-Body Irradiation Followed By Donor Stem Cell Transplant and Cyclosporine and Mycophenolate Mofetil in Treating HIV-Positive Patients With or Without Cancer
  9. Fludarabine Phosphate, Melphalan, and Low-Dose Total-Body Irradiation Followed by Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Hematologic Malignancies
  10. Graft-Versus-Host Disease Prophylaxis in Treating Patients With Hematologic Malignancies Undergoing Unrelated Donor Peripheral Blood Stem Cell Transplant
  11. High-Dose Busulfan and High-Dose Cyclophosphamide Followed By Donor Bone Marrow Transplant in Treating Patients With Leukemia, Myelodysplastic Syndrome, Multiple Myeloma, or Recurrent Hodgkin or Non-Hodgkin Lymphoma