Reduced-Intensity Allogeneic Hematopoietic Cell Transplantation as Second Transplantation for Patients With Disease Relapse or Myelodysplasia After Prior Autologous Transplantation
N/A
69 Years
Both
Leukemia, Lymphoma, Lymphoproliferative Disorder, Multiple Myeloma and Plasma Cell Neoplasm, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Neoplasms
Trial Information
Reduced-Intensity Allogeneic Hematopoietic Cell Transplantation as Second Transplantation for Patients With Disease Relapse or Myelodysplasia After Prior Autologous Transplantation
OBJECTIVES:
Primary
- To demonstrate the efficacy of performing reduced-intensity conditioning allogeneic
hematopoietic cell transplantation in patients with relapsed hematologic malignancies
or secondary myelodysplasia after completion of prior high-dose chemotherapy and
autologous hematopoietic stem cell transplantation.
- To compare the strategy of this regimen with the strategy used in CALGB-100002.
Secondary
- To describe the response rate at 6 and 12 months in patients treated with this regimen.
- To describe the time-to-progression in patients treated with this regimen.
- To determine the ability to use pharmacokinetic-directed busulfan to achieve AUC within
20% of target AUC in > 80% of patients.
- To determine percent of donor chimerism in T-cell, myeloid and B-cell populations
achieved with this regimen compared with CALGB-100002.
- To determine the risk of acute and chronic graft-versus-host disease and other
toxicities of this regimen in these patients.
- To describe the overall survival and disease-free survival of patients treated on this
regimen.
- To determine the rate of viral, bacterial, and fungal opportunistic infections
occurring in the first year after transplantation compared with CALGB-100002.
OUTLINE: This is a multicenter study.
- Preparative Regimen:
- Busulfan test dose: Patients receive busulfan IV over 45 minutes once during days
-14 and -9.
- Busulfan treatment dose: Patients receive fludarabine phosphate IV over 30 minutes
on days -7 to -3 and busulfan IV over 3 hours on days -6 to -3.
- Graft-vs-Host Disease (GVHD) Prophylaxis:
- HLA-identical donor: Patients receive antithymocyte globulin IV over 6-10 hours on
days -6 to -5; oral tacrolimus twice daily on days -2 to 90 followed by a taper*
as tolerated until day 150 or 180; and methotrexate IV on days 1, 3, and 6.
NOTE: * Tacrolimus may be tapered on days 60-90 if donor chimerism of CD3+ cells is < 50% at
day 60 or patient has progressive disease.
- Matched-unrelated donor: Patients receive antithymocyte globulin, tacrolimus, and
methotrexate as in HLA-identical donor regimen. Patients also receive oral
mycophenolate mofetil twice daily on days 0 to 60.
- Allogeneic Stem Cell Transplantation: Patients undergo allogeneic peripheral blood
stem cell transplantation on days 0 and 1. Patients then receive filgrastim
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.
Blood samples are collected at baseline and then periodically during study therapy for
pharmacokinetic studies.
After completion of study therapy, patients are followed up every 3 months for 2 years and
then every 6 months for up to 5½ years.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Histologically confirmed hematologic malignancies:
- Chronic lymphocytic leukemia (CLL) or prolymphocytic leukemia (PLL)
- Absolute lymphocytosis of > 5,000/μL
- Lymphocytes must appear morphologically mature with < 55% prolymphocytes
(CLL)
- Patients with > 55% prolymphocytes are considered as having PLL
- Lymphocyte phenotype with expression of CD20, CD19, and CD5 (CLL)
- Non-Hodgkin lymphoma
- Any WHO classification of histologic subtype
- Core biopsies acceptable for primary diagnosis and immunophenotyping
- Bone marrow biopsies as sole means of diagnosis not allowed for follicular
lymphoma
- Hodgkin lymphoma
- Any WHO classification of histologic subtype
- Core biopsies acceptable for primary diagnosis and immunophenotyping
- Bone marrow biopsy is required
- Multiple myeloma
- Patients must have active disease requiring treatment (Durie-Salmon stage
I-III)
- Acute myeloid leukemia
- Must have < 10% bone marrow blasts and no circulating blasts
- Myelodysplastic syndrome (MDS)
- MDS as define by WHO criteria
- Must have < 10% marrow blasts
- Relapsed or progressive disease or myelodysplasia ≥ 6 months after prior high-dose
chemotherapy with autologous hematopoietic cell support
- Prior syngeneic transplantation allowed
- Healthy donor meeting one of the following criteria:
- HLA-identical sibling (6/6)
- Serologic typing for class I (A, B) and molecular typing for class II
(DRB1) required
- 8/8 matched-unrelated donor
- Molecular identity at HLA A, B, C, and DRB1 by high-resolution typing
required
- No syngeneic donors
PATIENT CHARACTERISTICS:
- Creatinine clearance ≥ 40 mL/min
- Total bilirubin ≤ 2 mg/dL
- AST ≤ 3 times upper limit of normal
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- DLCO ≥ 40% with no symptomatic pulmonary disease
- LVEF ≥ 30% by MUGA or ECHO
- No uncontrolled diabetes mellitus or active serious infection
- No known hypersensitivity to E.coli-derived products
- No HIV infection
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- At least 4 weeks should elapse between prior standard cytotoxic chemotherapy,
radiation therapy, or surgery and the planned start of the preparative regimen on day
-7
Type of Study:
Interventional
Study Design:
Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Event-free survival (EFS)
Safety Issue:
No
Principal Investigator
Asad Bashey, MD, PhD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Blood and Marrow Transplant Group of Georgia
Authority:
United States: Federal Government
Study ID:
CDR0000667954
NCT ID:
NCT01118013
Start Date:
December 2010
Completion Date:
Related Keywords:
- Leukemia
- Lymphoma
- Lymphoproliferative Disorder
- Multiple Myeloma and Plasma Cell Neoplasm
- Myelodysplastic Syndromes
- Myelodysplastic/Myeloproliferative Neoplasms
- adult acute myeloid leukemia with 11q23 (MLL) abnormalities
- 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)
- juvenile myelomonocytic leukemia
- prolymphocytic leukemia
- recurrent adult acute myeloid leukemia
- recurrent adult T-cell leukemia/lymphoma
- recurrent childhood acute myeloid leukemia
- refractory chronic lymphocytic leukemia
- recurrent adult Hodgkin lymphoma
- recurrent adult Burkitt lymphoma
- recurrent adult diffuse large cell lymphoma
- recurrent adult diffuse mixed cell lymphoma
- recurrent adult diffuse small cleaved cell lymphoma
- recurrent adult grade III lymphomatoid granulomatosis
- recurrent adult immunoblastic large cell lymphoma
- recurrent adult lymphoblastic lymphoma
- recurrent childhood grade III lymphomatoid granulomatosis
- recurrent childhood large cell lymphoma
- recurrent childhood lymphoblastic lymphoma
- recurrent childhood small noncleaved cell lymphoma
- recurrent cutaneous T-cell non-Hodgkin lymphoma
- recurrent mycosis fungoides/Sezary syndrome
- recurrent grade 1 follicular lymphoma
- recurrent grade 2 follicular lymphoma
- recurrent grade 3 follicular lymphoma
- recurrent mantle cell lymphoma
- recurrent marginal zone lymphoma
- recurrent small lymphocytic lymphoma
- recurrent/refractory childhood Hodgkin lymphoma
- childhood diffuse large cell lymphoma
- childhood grade III lymphomatoid granulomatosis
- childhood immunoblastic large cell lymphoma
- childhood nasal type extranodal NK/T-cell lymphoma
- post-transplant lymphoproliferative disorder
- stage I multiple myeloma
- stage II multiple myeloma
- stage III multiple myeloma
- refractory multiple myeloma
- de novo myelodysplastic syndromes
- previously treated myelodysplastic syndromes
- secondary myelodysplastic syndromes
- childhood myelodysplastic syndromes
- recurrent childhood anaplastic large cell lymphoma
- adult acute myelomonocytic leukemia (M4)
- childhood acute myelomonocytic leukemia (M4)
- adult acute minimally differentiated myeloid leukemia (M0)
- childhood acute minimally differentiated myeloid leukemia (M0)
- adult acute myeloblastic leukemia without maturation (M1)
- childhood acute myeloblastic leukemia without maturation (M1)
- adult acute myeloblastic leukemia with maturation (M2)
- childhood acute myeloblastic leukemia with maturation (M2)
- adult acute promyelocytic leukemia (M3)
- childhood acute promyelocytic leukemia (M3)
- adult acute monoblastic leukemia (M5a)
- adult acute monocytic leukemia (M5b)
- childhood acute monoblastic leukemia (M5a)
- childhood acute monocytic leukemia (M5b)
- adult erythroleukemia (M6a)
- adult pure erythroid leukemia (M6b)
- childhood acute erythroleukemia (M6)
- adult acute megakaryoblastic leukemia (M7)
- childhood acute megakaryocytic leukemia (M7)
- childhood Burkitt lymphoma
- atypical chronic myeloid leukemia, BCR-ABL1 negative
- chronic myelomonocytic leukemia
- cutaneous B-cell non-Hodgkin lymphoma
- extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
- nodal marginal zone B-cell lymphoma
- splenic marginal zone lymphoma
- myelodysplastic/myeloproliferative neoplasm, unclassifiable
- Neoplasms
- Leukemia
- Lymphoma
- Lymphoproliferative Disorders
- Multiple Myeloma
- Neoplasms, Plasma Cell
- Plasmacytoma
- Myelodysplastic Syndromes
- Preleukemia
- Myeloproliferative Disorders
- Lymphoma, Large-Cell, Immunoblastic
- Myelodysplastic-Myeloproliferative Diseases
Name | Location |
|---|---|
| CCOP - Christiana Care Health Services | Wilmington, Delaware 19899 |
| Florida Hospital Cancer Institute at Florida Hospital Orlando | Orlando, Florida 32803-1273 |
| Wake Forest University Comprehensive Cancer Center | Winston-Salem, North Carolina 27157-1096 |
| Greenebaum Cancer Center at University of Maryland Medical Center | Baltimore, Maryland 21201 |
| New York Weill Cornell Cancer Center at Cornell University | New York, New York 10021 |
| Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis | St. Louis, Missouri 63110 |
| Cancer Institute of New Jersey at Cooper - Voorhees | Voorhees, New Jersey 08043 |
| Tunnell Cancer Center at Beebe Medical Center | Lewes, Delaware 19958 |
| Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center | Columbus, Ohio 43210-1240 |
| Union Hospital of Cecil County | Elkton MD, Maryland 21921 |
