Donor Stem Cell Transplant in Treating Patients With High-Risk Hematologic Cancer
|ClinicalTrials.gov Identifier: NCT00818961|
Recruitment Status : Terminated (terminated early due to meeting end point with fewer patients than anticipated)
First Posted : January 8, 2009
Results First Posted : December 18, 2013
Last Update Posted : December 18, 2013
RATIONALE: Giving low doses of chemotherapy before a donor stem cell transplant helps stop the growth of cancer cells. It may also 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 a monoclonal antibody, such as alemtuzumab, before transplant and tacrolimus and methotrexate after transplant may stop this from happening.
PURPOSE: This phase II trial is studying the side effects of donor stem cell transplant and to see how well it works in treating patients with high-risk hematologic cancer.
|Condition or disease||Intervention/treatment||Phase|
|Leukemia Lymphoma Myelodysplastic Syndromes Myelodysplastic/Myeloproliferative Diseases||Biological: alemtuzumab Biological: graft-versus-tumor induction therapy Biological: rituximab Drug: busulfan Drug: cyclophosphamide Drug: fludarabine phosphate Drug: methotrexate Drug: tacrolimus Procedure: allogeneic bone marrow transplantation||Phase 2|
- To evaluate the safety and toxicity of a reduced-intensity conditioning regimen followed by allogeneic bone marrow or peripheral blood stem cell transplantation from an HLA-matched unrelated donor in patients with high-risk hematologic malignancies.
- To evaluate engraftment by peripheral blood chimerism analysis.
- To determine the incidence and severity of acute and chronic graft-versus-host disease following the transplant.
- To examine the possibility of controlling hematologic malignancies by induction of a graft-versus-leukemia/tumor effect.
- To determine the disease-free survival, relapse, transplant-related mortality, and death from all causes.
Reduced-intensity conditioning regimen: Patients receive 1 of 2 conditioning regimens according to diagnosis.
- Regimen 1 (acute leukemia, myelodysplastic syndromes, myeloproliferative syndrome, or chronic myelogenous leukemia): Patients receive fludarabine phosphate IV over 30 minutes and busulfan IV over 3 hours on days -6 to -3 or orally 4 times daily on days -7 to -3.
- Regimen 2 (lymphoproliferative malignancies): Patients receive fludarabine phosphate IV over 30 minutes and cyclophosphamide IV over 1 hour on days -5 to -3. Patients with CD20+ malignancies also receive rituximab IV over 4-6 hours on days -13, -6, 1, and 8.
- Transplantation: Patients undergo allogeneic bone marrow or peripheral blood stem cell transplantation on day 0.
- Graft-versus-host disease (GVHD) prophylaxis: Patients receive low-dose alemtuzumab subcutaneously on days -11 to -9 and tacrolimus IV over 24 hours beginning on day -3 and then orally twice daily beginning on day 14 and continuing until day 60, followed by a taper until day 180 in the absence of clinically significant GVHD. Patients also receive methotrexate on days 1, 3, and 6.
Patients who exhibit persistent mixed chimerism or disease relapse/progression despite full withdrawal of immunosuppression may receive up to 3 donor lymphocyte infusions.
Blood samples are taken on days 30, 60, and 100 and then every 4 weeks thereafter for chimerism studies by PCR analysis.
After completion of study therapy, patients are followed periodically for up to 60 months.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||36 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Reduced Intensity Allogeneic Stem Cell Transplantation With Matched Unrelated Donors for Patients With Hematologic Malignancies|
|Study Start Date :||May 2005|
|Primary Completion Date :||March 2011|
|Study Completion Date :||March 2012|
Hematopoietic Stem Cell Transplantation
All patients receive a hematopoietic stem cell transplant using one of two chemotherapy regimens based on donor type
43 mg subcutaneously over 3 days (3 mg on day -11, 10 mg on day -10, 30 mg on day -9)
Other Name: CampathBiological: graft-versus-tumor induction therapy
curative potential of allogeneic transplant results from the immune anti-tumor effect of donor cells or GVT/GVLBiological: rituximab
in patients with Cd20+ malignancies: rituximab 375 mg/m*2 day -13. rituximab 1000 mg/m*2 on days, -6, +1, +8.
Other Name: RituxanDrug: busulfan
For patients with AML, CML, MDS, MPS and ALL only: IV or oral busulfan may be given IV busulfan: 130 mg/m2 over 3 hours once daily on days -6, -5, -4 and -3 Oral busulfan: taken every 6 hours x 15 doses beginning on day -7 at 6pm and continuing through day -3 at 6am. 1 mg/kg test dose will be given prior to day -7 and PK samples will be drawn to calculate AUC.Drug: cyclophosphamide
750 mg/m2 infused over 1 hour once daily on days -5, -4 and -3. Cyclophosphamide will be started approximately 4 hours after the start of Fludarabine
Other Name: CytoxanDrug: fludarabine phosphate
For patients with CLL, NHL & HD: 30 mg/m2 infused over 30 minutes once daily on days -5, -4 and -3 For patients with AML, CML, MDS, MPS and ALL: 40 mg/m2 infused over 30 minutes once daily on days -6, -5, -4 and -3.
Other Name: FludaraDrug: methotrexate
5 mg/m2 administered on days +1, +3 and +6Drug: tacrolimus
0.03mg/kg/day infused over 24 hours starting on day -1 and switched to oral (twice daily divided dose) on day 14 or when able to tolerate PO
Other Name: Prograf; FK506Procedure: allogeneic bone marrow transplantation
Recipients will receive an allogeneic transplant on day 0 after receiving high-dose chemotherapy. This trial uses matched unrelated donor stem cells.
Other Name: HSCT, allo transplant
- Survival at Day 100 [ Time Frame: 100 day ]Survival at Day 100
- Overall Survival at 1 Year [ Time Frame: 1 year ]Evaluation of overall survival at 1 year (# of patients who are alive at 1 year post-transplant)
- Non-relapse Mortality at Day 100 [ Time Frame: Day 100 ]patients are evaluable for their cause of death at Day 100
- Non-relapse Mortality at 1 Year Post-transplant [ Time Frame: 1 year ]Number of patients who died of non-relapse causes at one year. this is in clusive of all patients who were transplanted on study even though only 10 patients died at by 1 year time point. This outcome will be referenced in the donor chimerism outcome. Only 26/36 patients were eligible for this time point as that is all that were alive.
- Complete Donor Chimerism [ Time Frame: 2 years ]Complete donor chimerism (defined as >/= 95% donor cells in peripheral blood CD3+ and CD33+ was measured.
- Neutrophil Recovery [ Time Frame: Day 100 ]The number of patients experiencing neutrophil recovery post transplant
- Platelet Engraftment [ Time Frame: Day 100 ]The number of patients experiencing platelet engraftment post-transplant
- Number of Patients Requiring the Use of Donor Leukocyte Infusion (DLI) for Early Mixed T-cell Chimerism [ Time Frame: Day 100 ]DLI is used for patients with mixed chimerism following transplant
- Number of Patients Experiencing Grade 2-4 Acute Graft-versus-host Disease Post-transplant [ Time Frame: patients were followed for 2 years ]patients experiencing acute graft versus host disease post-transplant
- Number of Patients Experiencing Chronic Graft Versus Host Disease [ Time Frame: >100 days post-transplant ]
- Number of Patients Experiencing Veno-occlusive Disease (VOD) Post-transplant [ Time Frame: 4 years ]Patients will be evaluated up to 4 years post transplant
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00818961
|United States, Georgia|
|Blood and Marrow Transplant Group of Georgia|
|Atlanta, Georgia, United States, 30342|
|Principal Investigator:||Scott R. Solomon, MD||Blood and Marrow Transplant Group of Georgia|