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


Phase 1/Phase 2
N/A
N/A
Open (Enrolling)
Both
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-ABL1 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, 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, 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 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 Mantle Cell Lymphoma, Stage III Marginal Zone Lymphoma, Stage III Multiple Myeloma, Stage III Small Lymphocytic Lymphoma, 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 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 Small Lymphocytic Lymphoma

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Trial Information

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


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 on days -3 to 56 and mycophenolate mofetil PO once daily 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.


Inclusion Criteria:



- Patients having received a preceding allogeneic transplantation from either a
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; additionally, all other immunosuppressive therapy will be
discontinued before administration of pentostatin

- 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

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Safety of the combined use of pentostatin and DLI as defined by an acceptable rate of grade IV acute GVHD

Outcome Description:

Reported following the Fred Hutchinson Cancer Research Center (FHCRC) Guidelines for serious adverse event (SAE) reporting.

Outcome Time Frame:

Within 100 days after the last DLI

Safety Issue:

Yes

Principal Investigator

Brenda Sandmaier

Investigator Role:

Principal Investigator

Investigator Affiliation:

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Authority:

United States: Federal Government

Study ID:

1825.00

NCT ID:

NCT00096161

Start Date:

May 2003

Completion Date:

Related Keywords:

  • 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-ABL1 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
  • 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
  • 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 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 Mantle Cell Lymphoma
  • Stage III Marginal Zone Lymphoma
  • Stage III Multiple Myeloma
  • Stage III Small Lymphocytic Lymphoma
  • 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 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 Small Lymphocytic Lymphoma
  • Congenital Abnormalities
  • Primary Myelofibrosis
  • Blast Crisis
  • Burkitt Lymphoma
  • Neoplasms
  • Hodgkin Disease
  • Leukemia
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Leukemia, Lymphoid
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid
  • Leukemia, Myeloid, Accelerated Phase
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive
  • Leukemia, Myeloid, Chronic-Phase
  • Leukemia, Myelomonocytic, Chronic
  • Leukemia, Neutrophilic, Chronic
  • Lymphoma
  • Lymphoma, Follicular
  • Lymphoma, Large B-Cell, Diffuse
  • Lymphoma, Non-Hodgkin
  • Multiple Myeloma
  • Neoplasms, Plasma Cell
  • Myelodysplastic Syndromes
  • Preleukemia
  • Leukemia, Myelomonocytic, Acute
  • Myeloproliferative Disorders
  • Lymphoma, B-Cell
  • Lymphoma, Large-Cell, Immunoblastic
  • Hypereosinophilic Syndrome
  • Lymphoma, B-Cell, Marginal Zone
  • Lymphoma, Mantle-Cell
  • Leukemia, Myelomonocytic, Juvenile
  • Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative
  • Myelodysplastic-Myeloproliferative Diseases

Name

Location
LDS Hospital Salt Lake City, Utah  84143
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium Seattle, Washington  98109
VA Puget Sound Health Care System Seattle, Washington  98101
Huntsman Cancer Institute/University of Utah Salt Lake City, Utah  84112