Pre-administration of Rabbit Antithymocyte Globulin to Optimize Donor T-Cell Engraftment Following Reduced Intensity Allogeneic Peripheral Blood Progenitor Cell Transplantation From Matched-Related Donors
N/A
75 Years
Both
Myeloproliferative Disorders, Kidney Cancer, Leukemia, Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Diseases
Trial Information
Pre-administration of Rabbit Antithymocyte Globulin to Optimize Donor T-Cell Engraftment Following Reduced Intensity Allogeneic Peripheral Blood Progenitor Cell Transplantation From Matched-Related Donors
OBJECTIVES:
- To assess the percentage of patients with hematological malignancies or renal cell
carcinoma who achieve > 90% donor T-cell chimerism at 30 days after treatment with
reduced-intensity conditioning comprising low-dose anti-thymocyte globulin, low-dose
cyclophosphamide, busulfan, and fludarabine phosphate followed by allogeneic peripheral
blood progenitor cell transplantation from a matched related donor.
- To assess the incidence of severe (grade 3 or 4) acute graft-versus-host disease (GVHD)
and extensive chronic GVHD in these patients.
- To assess whether this regimen is associated with reduced transplant-related toxicity
and increased tolerability in these patients.
- To assess the overall safety of this conditioning regimen as measured by 6-month
transplant-related mortality in these patients.
- To determine the efficacy of this regimen in inducing durable remissions in these
patients.
OUTLINE:
- Reduced-intensity conditioning (RIC): Patients receive anti-thymocyte globulin IV over
4-6 hours on day -16 and over 6-8 hours on day -15, fludarabine phosphate IV over 30
minutes on days -7 to -3, busulfan IV over 3 hours on days -4 and -3, and
cyclophosphamide IV over 1-2 hours on day -2.
- Transplantation: Patients undergo allogeneic peripheral blood progenitor cell
transplantation on day 0.
- Graft-vs-host disease (GVHD) prophylaxis: Patients receive oral tacrolimus every 12
hours on days -1 to 90, followed by a taper until day 150. Patients also receive
methotrexate IV on days 1, 3, and 6.
Blood samples are collected periodically for pharmacokinetic studies of anti-thymocyte
globulin and PCR analysis for chimerism.
After completion of study therapy, patients are followed periodically for up to 3 years.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Histologically confirmed diagnosis of one of the following:
- Chronic myeloid leukemia (CML)
- Philadelphia chromosome (Ph)- and/or BCR-ABL-positive disease
- In chronic or accelerated phase
- Suboptimal response to imatinib mesylate (i.e., no hematologic complete
response by 3 months, no major cytogenetic response by 6 months, or no
complete cytogenetic response by 1 year)
- CML in blastic transformation allowed provided patient achieved complete
remission (CR) or second chronic phase after treatment with imatinib
mesylate or chemotherapy
- Chronic lymphocytic leukemia meeting one of the following criteria:
- Rai stage III or IV disease
- Rai stage I or II disease that failed standard therapy (i.e., disease is
progressing after ≥ 1 course of standard therapy)
- Non-Hodgkin lymphoma (NHL) meeting one of the following criteria:
- Indolent NHL
- Clinical stage III or IV disease or bulky stage II disease (i.e., ≥
one lymphoid mass > 5 cm in ≥ one dimension)
- Relapsed after primary therapy OR is refractory to therapy
- Aggressive NHL
- Is not considered curable with standard chemotherapy or autologous
stem cell transplantation (i.e., relapsed after autologous stem cell
transplantation)
- Chemotherapy-responsive disease
- Multiple myeloma
- Durie-Salmon stage II or III disease
- Durie Salmon stage I disease allowed provided β2 microglobulin level >
3 mg/dL
- Acute myeloid leukemia or acute lymphocytic leukemia
- In CR (defined as < 5% blasts in bone marrow and no circulating blasts) AND
has any of the following poor prognostic features:
- WBC > 100,000/mm^3 at presentation
- In second or greater remission
- Adverse-risk cytogenetics (i.e., Ph1-positive, 11q23 translocation,
-5, -7, complex translocations, or other recognized adverse-risk
cytogenetics)
- Renal cell carcinoma
- Stage IV disease
- Clear cell morphology
- Myelodysplastic syndromes
- Bone marrow blasts ≤ 10% on last bone marrow biopsy prior to
transplantation
- Myeloproliferative disease
- Anticipated life expectancy on conventional therapy < 10 years
- No uncomplicated essential thrombocythemia or primary polycythemia
- Hodgkin lymphoma
- Relapsed after ≥ 1 standard-dose chemotherapy regimen
- Not considered curable by autologous stem cell transplantation
- No clinical evidence of active CNS involvement
- Previously treated leptomeningeal disease allowed provided CSF cytology is
negative at the time of assessment for transplantation
- Available 6/6 allele match (i.e., HLA-A, B, DRβ1)matched related donor
PATIENT CHARACTERISTICS:
- ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%
- Bilirubin < 3 times normal (unless abnormality due to malignancy)
- AST and ALT < 3 times normal (unless abnormality due to malignancy)
- Creatinine ≤ 2.0 mg/dL
- LVEF ≥ 40% by MUGA or ECHO
- DLCO ≥ 40% of predicted
- FEV-1 ≥ 50% of predicted
- Not pregnant or nursing
- Fertile patients must use effective contraception
- Deemed to be an appropriate candidate for allogeneic SCT
- No evidence of myocardial infarction within the past 6 months
- No psychological or social condition that may interfere with study participation
- No serious uncontrolled localized or active systemic infection
- No second malignancy within the past 3 years except for completely excised
nonmelanotic skin cancer or in situ carcinoma of the cervix
- No chronic inflammatory disorder requiring the continued use of glucocorticoids or
other immunosuppressive medications
- No known HIV positivity
- No hypersensitivity to E. coli-derived proteins
Type of Study:
Interventional
Study Design:
Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Achievement of > 90% (Full) Donor Chimerism in the T-cell Lineage as Measured by PCR at Day 30 Post-transplantation
Outcome Description:
Chimerism analysis of peripheral blood mononuclear cells using PCR for STR/VNTR will be performed post transplant. On each occasion, the peripheral blood will be separated into the T-cell component (using e.g. CD3 selection) and the myeloid component (using e.g.CD14/15 selection) before assessment of chimerism.
Outcome Time Frame:
Day 30
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: Food and Drug Administration
Study ID:
CDR0000618483
NCT ID:
NCT00787761
Start Date:
April 2007
Completion Date:
May 2012
Related Keywords:
- Myeloproliferative Disorders
- Kidney Cancer
- Leukemia
- Lymphoma
- Multiple Myeloma and Plasma Cell Neoplasm
- Myelodysplastic Syndromes
- Myelodysplastic/Myeloproliferative Diseases
- accelerated phase CML
- blastic phase CML
- Philadelphia chromosome positive CML
- stage I CLL
- stage II CLL
- stage III CLL
- stage IV CLL
- stage I multiple myeloma
- stage II multiple myeloma
- stage III multiple myeloma
- adult AML with 11q23 (MLL) abnormalities
- adult CML in remission
- adult ALL in remission
- stage IV renal cell cancer
- de novo MDS
- previously treated MDS
- secondary MDS
- atypical CML, BCR-ABL negative
- chronic myelomonocytic leukemia
- MDS/myeloproliferative neoplasm, unclassifiable
- primary myelofibrosis
- chronic neutrophilic leukemia
- recurrent adult Hodgkin lymphoma
- clear cell renal cell carcinoma
- adult AML with inv(16)(p13;q22)
- adult AML with t(15;17)(q22;q12)
- adult AML with t(16;16)(p13;q22)
- adult AML with t(8;21)(q22;q22)
- adult nasal type extranodal NK/T-cell lymphoma
- AML/transient myeloproliferative disorder
- Burkitt lymphoma
- chronic phase CML
- extranodal marginal zone B-cell lymphoma of mucosa tissue
- nodal marginal zone B-cell lymphoma
- stage III adult Burkitt lymphoma
- stage IV adult Burkitt lymphoma
- recurrent adult Burkitt lymphoma
- stage III adult diffuse large cell lymphoma
- stage III adult diffuse mixed cell lymphoma
- recurrent adult diffuse large cell lymphoma
- stage IV adult diffuse large cell lymphoma
- stage IV adult diffuse mixed cell lymphoma
- recurrent adult diffuse mixed cell lymphoma
- stage III adult immunoblastic large cell lymphoma
- stage IV adult immunoblastic large cell lymphoma
- stage III adult lymphoblastic lymphoma
- stage IV adult lymphoblastic lymphoma
- recurrent adult immunoblastic large cell lymphoma
- recurrent adult lymphoblastic lymphoma
- recurrent grade 3 follicular lymphoma
- stage III grade 3 follicular lymphoma
- stage IV grade 3 follicular lymphoma
- recurrent mantle cell lymphoma
- stage III mantle cell lymphoma
- stage IV mantle cell lymphoma
- contiguous st II adult diffuse small cleaved cell lymphoma
- noncontiguous st II diffuse small cleaved cell lymphoma
- recurrent adult diffuse small cleaved cell lymphoma
- stage III adult diffuse small cleaved cell lymphoma
- stage IV adult diffuse small cleaved cell lymphoma
- contiguous stage II grade 1 follicular lymphoma
- contiguous stage II grade 2 follicular lymphoma
- noncontiguous stage II grade 1 follicular lymphoma
- noncontiguous stage II grade 2 follicular lymphoma
- recurrent grade 1 follicular lymphoma
- recurrent grade 2 follicular lymphoma
- stage III grade 1 follicular lymphoma
- stage III grade 2 follicular lymphoma
- stage IV grade 1 follicular lymphoma
- stage IV grade 2 follicular lymphoma
- contiguous stage II marginal zone lymphoma
- noncontiguous stage II marginal zone lymphoma
- recurrent marginal zone lymphoma
- stage III marginal zone lymphoma
- stage IV marginal zone lymphoma
- contiguous stage II small lymphocytic lymphoma
- noncontiguous stage II small lymphocytic lymphoma
- recurrent small lymphocytic lymphoma
- stage III small lymphocytic lymphoma
- stage IV small lymphocytic lymphoma
- recurrent adult grade III lymphomatoid granulomatosis
- relapsing chronic myelogenous leukemia
- refractory chronic lymphocytic leukemia
- splenic marginal zone lymphoma
- Waldenstrom macroglobulinemia
- recurrent adult T-cell leukemia/lymphoma
- stage III adult T-cell leukemia/lymphoma
- stage IV adult T-cell leukemia/lymphoma
- anaplastic large cell lymphoma
- angioimmunoblastic T-cell lymphoma
- Neoplasms
- Carcinoma, Renal Cell
- Kidney Neoplasms
- Leukemia
- Lymphoma
- Lymphoma, Non-Hodgkin
- Multiple Myeloma
- Neoplasms, Plasma Cell
- Plasmacytoma
- Myelodysplastic Syndromes
- Preleukemia
- Myeloproliferative Disorders
- Lymphoma, Large-Cell, Immunoblastic
- Myelodysplastic-Myeloproliferative Diseases
Name | Location |
|---|---|
| Blood and Marrow Transplant Group of Georgia | Atlanta, Georgia 30342-1601 |
