Non-Myeloablative Allogeneic Hematopoietic Cell Transplantation For Patients With Disease Relapse Or Myelodysplasia After Prior Autologous Transplantation
N/A
69 Years
Both
Leukemia, Lymphoma, Multiple Myeloma, Plasma Cell Neoplasm, Myelodysplastic Syndromes, Myeloproliferative Neoplasms
Trial Information
Non-Myeloablative Allogeneic Hematopoietic Cell Transplantation For Patients With Disease Relapse Or Myelodysplasia After Prior Autologous Transplantation
OBJECTIVES:
- Determine the feasibility of non-myeloablative allogeneic hematopoietic stem cell
transplantation by demonstrating that the risk of treatment-related mortality during
the first 6 months is an acceptable rate of less than 40% in patients with relapsed
hematologic malignancies after prior high-dose chemotherapy and autologous stem cell
transplantation.
- Determine the response rates (disease-specific partial and complete response) in
patients treated with this regimen.
- Determine the 6-month and 12-month probabilities of response in patients treated with
this regimen.
- Determine the distribution of time-to-progression in patients responding to this
regimen.
- Determine the percent donor chimerism in patients treated with this regimen.
- Determine the risk of acute and chronic graft-vs-host disease in patients treated with
this regimen.
- Determine the toxic effects of this regimen in these patients.
- Determine the disease-free and overall survival of patients treated with this regimen.
OUTLINE: This is an open-label study.
- Preparative Regimen: Patients receive fludarabine IV over 30 minutes on days -7 to -3
and busulfan IV over 2 hours every 6 hours (for a total of 8 doses) on days -4 and -3.
- Graft vs Host Disease (GVHD) Prophylaxis: Patients who have an HLA-identical donor
receive oral (or IV if unable to tolerate oral administration) tacrolimus twice daily
on days -1 to 90 followed by a taper^* until day 150 and methotrexate IV on days 1, 3,
and 6. Patients with a matched related or matched unrelated donor receive oral (or IV
if unable to tolerate oral administration) tacrolimus twice daily on days -1 to 180
followed by a taper^* as tolerated; methotrexate IV on days 1, 3, 6, and 11; oral
mycophenolate mofetil twice daily on days -2 to 60 followed by a taper; and rabbit
anti-thymocyte globulin IV over 4-6 hours on days -4 to -1 (for a total of 4 doses).
NOTE: *Tacrolimus may be tapered on days 60-90 if donor chimerism of CD3+ cells is less than
50% at day 60 or patient has progressive disease
- Allogeneic Stem Cell Transplantation: Patients undergo allogeneic bone marrow or
peripheral blood stem cell transplantation on days 0 and 1. Patients then receive
filgrastim (G-CSF) subcutaneously daily beginning on day 7 and continuing until blood
counts recover.
- Donor Lymphocyte Infusion (DLI): After day 180 (or day 210 for patients without an
HLA-identical donor), patients with stable or progressive disease and no active GVHD
may receive up to 3 DLIs every 8 weeks.
Patients are followed within 2-3 months, every 3 months for 2 years, and then every 6 months
for 3 years.
PROJECTED ACCRUAL: A total of 20-80 patients will be accrued for this study within 10-40
months.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Histologically confirmed hematologic malignancy, including one of the following:
- Chronic lymphocytic leukemia (CLL)
- Absolute lymphocytosis greater than 5,000/mm^3
- Lymphocytes must appear morphologically mature with less than 55%
prolymphocytes
- Lymphocyte phenotype with expression of CD19 and CD5
- Prolymphocytic leukemia (PLL)
- Morphologically confirmed
- Absolute lymphocytosis greater than 5,000/mm^3
- More than 55% prolymphocytes
- Non-Hodgkin's lymphoma or Hodgkin's lymphoma
- Any WHO histologic subtype allowed except mantle cell lymphoma
- Core biopsies allowed if they contain adequate tissue for primary diagnosis
and immunophenotyping
- No bone marrow biopsy as the sole diagnostic means for follicular lymphoma
- Multiple myeloma
- Active disease requiring treatment
- Durie-Salmon stage I, II, or III
- Acute myeloid leukemia
- Documented control (i.e., less than 10% bone marrow blasts and no
circulating blasts)
- Myelodysplastic syndromes
- Documented disease by WHO criteria
- Must have evidence of relapse/progression at least 6 months after prior high-dose
chemotherapy with autologous hematopoietic stem cell support
- Absence of CD23 expression for CLL or PLL allowed provided there is no morphologic
evidence of mantle cell lymphoma
- Availability of any of the following donor types:
- HLA-identical sibling (6/6)
- 9/10 matched related donor by high-resolution molecular typing at HLA A, B, C,
DRB1, and DQB1 loci
- Only a single mismatch at one class I or II allele allowed
- 10/10 matched unrelated donor by high-resolution molecular typing at HLA A, B,
C, DRB1, and DQB1 loci
- No syngeneic donors
PATIENT CHARACTERISTICS:
Age
- Under 70
Performance status
- Not specified
Life expectancy
- Not specified
Hematopoietic
- See Disease Characteristics
Hepatic
- Bilirubin no greater than 3 times upper limit of normal (ULN)
- AST no greater than 3 times ULN
Renal
- Creatinine clearance at least 40 mL/min
Cardiovascular
- LVEF at least 30% by MUGA
Pulmonary
- DLCO greater than 40%
- No symptomatic pulmonary disease
Other
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- HIV negative
- No uncontrolled diabetes mellitus
- No active serious infection
- No known hypersensitivity to E. coli-derived products
PRIOR CONCURRENT THERAPY:
Biologic therapy
- See Disease Characteristics
Chemotherapy
- See Disease Characteristics
- More than 4 weeks since prior chemotherapy
Endocrine therapy
- Not specified
Radiotherapy
- More than 4 weeks since prior radiotherapy
Surgery
- More than 4 weeks since prior surgery
Type of Study:
Interventional
Study Design:
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Treatment-related mortality
Outcome Time Frame:
6 months post transplant
Safety Issue:
Yes
Principal Investigator
Asad Bashey, MD, PhD
Investigator Role:
Study Chair
Investigator Affiliation:
University of California, San Diego
Authority:
United States: Federal Government
Study ID:
CDR0000269301
NCT ID:
NCT00053196
Start Date:
December 2002
Completion Date:
August 2010
Related Keywords:
- Leukemia
- Lymphoma
- Multiple Myeloma
- Plasma Cell Neoplasm
- Myelodysplastic Syndromes
- Myeloproliferative Neoplasms
- refractory chronic lymphocytic leukemia
- prolymphocytic leukemia
- recurrent adult Hodgkin lymphoma
- stage I multiple myeloma
- stage II multiple myeloma
- stage III multiple myeloma
- refractory multiple myeloma
- previously treated myelodysplastic syndromes
- recurrent adult diffuse large cell lymphoma
- recurrent adult diffuse mixed cell lymphoma
- recurrent adult diffuse small cleaved cell lymphoma
- recurrent adult Burkitt lymphoma
- recurrent adult immunoblastic large cell lymphoma
- recurrent grade 1 follicular lymphoma
- recurrent grade 2 follicular lymphoma
- recurrent grade 3 follicular lymphoma
- secondary myelodysplastic syndromes
- de novo myelodysplastic syndromes
- recurrent adult acute myeloid leukemia
- recurrent childhood acute myeloid leukemia
- recurrent childhood large cell lymphoma
- recurrent childhood lymphoblastic lymphoma
- recurrent childhood small noncleaved cell lymphoma
- recurrent/refractory childhood Hodgkin lymphoma
- atypical chronic myeloid leukemia, BCR-ABL negative
- myelodysplastic/myeloproliferative neoplasm, unclassifiable
- recurrent marginal zone lymphoma
- recurrent small lymphocytic lymphoma
- extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
- nodal marginal zone B-cell lymphoma
- splenic marginal zone lymphoma
- adult acute myeloid leukemia with t(8;21)(q22;q22)
- adult acute myeloid leukemia with t(16;16)(p13;q22)
- adult acute myeloid leukemia with inv(16)(p13;q22)
- adult acute myeloid leukemia with 11q23 (MLL) abnormalities
- adult acute myeloid leukemia with t(15;17)(q22;q12)
- childhood myelodysplastic syndromes
- Neoplasms
- Leukemia
- Lymphoma
- Multiple Myeloma
- Neoplasms, Plasma Cell
- Plasmacytoma
- Myelodysplastic Syndromes
- Preleukemia
- Myeloproliferative Disorders
Name | Location |
|---|---|
| Roswell Park Cancer Institute | Buffalo, New York 14263 |
| CCOP - Christiana Care Health Services | Wilmington, Delaware 19899 |
| Siteman Cancer Center at Barnes-Jewish Hospital | Saint Louis, Missouri 63110 |
| Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University | Columbus, Ohio 43210-1240 |
| Rebecca and John Moores UCSD Cancer Center | La Jolla, California 92093-0658 |
| Wake Forest University Comprehensive Cancer Center | Winston-Salem, North Carolina 27157-1096 |
| Massey Cancer Center at Virginia Commonwealth University | Richmond, Virginia 23298-0037 |
| Cancer Institute of New Jersey at the Cooper University Hospital - Voorhees | Camden, New Jersey 08103 |
| Beebe Medical Center | Lewes, Delaware 19958 |
| St. Francis Hospital | Wilmington, Delaware 19805 |
| Union Hospital Cancer Center at Union Hospital | Elkton MD, Maryland 21921 |
| Western Pennsylvania Cancer Institute at Western Pennsylvania Hospital | Pittsburgh, Pennsylvania 15224-1791 |
