Ignite Creation Date:
2024-05-05 @ 11:21 AM
Last Modification Date:
2024-10-26 @ 9:04 AM
Study NCT ID:
NCT00003838
Status:
COMPLETED
Last Update Posted:
2023-09-21
First Post:
1999-11-01
Brief Title:
Specialized Blood Cell Transplants for Cancers of the Blood and Bone Marrow
Sponsor:
National Heart Lung and Blood Institute NHLBI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Non-Myeloablative Allogeneic Peripheral Blood Mobilized Hematopoietic Precursor Cell Transplantation for Hematologic Malignancies in High Risk Patients and in Patients With Debilitating Hematologic Diseases
Status:
COMPLETED
Status Verified Date:
2022-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The are a variety of cancerous diseases of the blood and bone marrow that can be potentially cured by bone marrow transplantation BMT Diseases like leukemia lymphoma and multiple myeloma are among the conditions that can be treated with BMT
Some patients with these diseases can be treated with medical chemotherapy alone However patients who relapse following chemotherapy are usually not curable with additional chemotherapy treatments The only option known to provide a potential cure if this occurs is BMT
Allogenic transplants are cells collected from relatives of the patient The transplant requires additional high intensity chemotherapy and radiation in order to destroy cancerous cells In the process many normal bone marrow cells are also destroyed This is the reason for transplanting stem cells The stem cells help to build new functioning bone marrow red cells white cells and platelets In addition the immune cells from the donor are implanted into the recipient s body and help to fight off infection and kill remaining cancerous cells
Unfortunately the powerful doses of chemotherapy and radiation therapy associated with allogenic BMT have toxic side effects and often make BMTs too dangerous to attempt in many patients
In order to reduce the complications of BMT and make it a safer available option for patients with cancers of the blood and bone marrow researchers have developed a new approach to the BMT
In this study researchers plan to use stem cells collected from the blood stream of patient s relatives rather than from the bone marrow blood progenitorstem cell transplant In addition researchers plan to use low doses of chemotherapy and no radiation therapy to reduce side effects The majority of the cancer killing effect will be the responsibility of the stem cell transplant rather than the chemotherapy
Some patients with these diseases can be treated with medical chemotherapy alone However patients who relapse following chemotherapy are usually not curable with additional chemotherapy treatments The only option known to provide a potential cure if this occurs is BMT
Allogenic transplants are cells collected from relatives of the patient The transplant requires additional high intensity chemotherapy and radiation in order to destroy cancerous cells In the process many normal bone marrow cells are also destroyed This is the reason for transplanting stem cells The stem cells help to build new functioning bone marrow red cells white cells and platelets In addition the immune cells from the donor are implanted into the recipient s body and help to fight off infection and kill remaining cancerous cells
Unfortunately the powerful doses of chemotherapy and radiation therapy associated with allogenic BMT have toxic side effects and often make BMTs too dangerous to attempt in many patients
In order to reduce the complications of BMT and make it a safer available option for patients with cancers of the blood and bone marrow researchers have developed a new approach to the BMT
In this study researchers plan to use stem cells collected from the blood stream of patient s relatives rather than from the bone marrow blood progenitorstem cell transplant In addition researchers plan to use low doses of chemotherapy and no radiation therapy to reduce side effects The majority of the cancer killing effect will be the responsibility of the stem cell transplant rather than the chemotherapy
Detailed Description:
Patients with malignant and non-malignant hematologic diseases including severe aplastic anemia SAA paroxysmal nocturnal hemoglobinuria PNH myelodysplastic syndrome MDS acute and chronic leukemias Hodgkins and non-Hodgkins lymphoma and multiple myeloma MM can now be cured by allogeneic bone marrow transplantation BMT This curative effect has been ascribed to the use of high dose chemo-radiotherapy and the anti-tumor or anti-bone marrow effect of the allograft Dose intensification of conditioning regimens in attempts to reduce disease recurrence has been largely unsuccessful because of increased toxicity and mortality Indeed most evidence now points to donor-derived T-cells as being the principal modality leading to the complete eradication of both malignant and non-malignant host hematopoietic cells
The assumption that successful allogeneic BMT relies on the myeloablative effect of intensive but hazardous chemo-radiotherapy has largely restricted this therapeutic modality to patients with malignant or life-threatening hematologic disorders under the age of 55 years Treatment-related mortality increases substantially with age prior intensive treatment with chemo-radiotherapy worsening performance status and co-morbid medical conditions An unacceptable risk of death from conventional BMT renders many patients ineligible for what may otherwise be curative therapy
Several in vitro studies have demonstrated the existence of donor-derived CD4 and CD8 positive lymphocytes with specific reactivity for the patient s leukemia These cells provide a potent graft-versus-leukemia GVL effect This GVL effect is best seen in patients with CML relapsing after BMT where a single infusion of donor lymphocytes has been shown to induce complete remission In addition to the potent anti-leukemia effect of these cells there is now strong evidence that donor T-cells are capable of completely eradicating residual host hematopoietic cells in a non-myeloablative transplant setting graft-versus-marrow leading to successful and complete donor hematopoietic engraftment
Non-myeloablative allogenic peripheral blood stem cell transplants are currently being investigated in phase III trials assessing engraftment efficacy and toxicity at a number of transplant centers Preliminary data including our own experience with greater than 150 patients undergoing this type of procedure have shown a high rate of complete donor engraftment with a low toxicity profile Two recent studies investigating non-myeloablative allo-transplantation in standard risk patients revealed an extremely low rate of transplant-related complications and mortality
The decreased risk of transplant-related complications associated with non-myeloablative transplants expands the eligibility of transplant candidates as well as opens the possibility to evaluate non-myeloablative regimens in patients at high risk for complications with standard transplantation Besides hematologic malignancies allogeneic BMT has been shown to be curative in a number of debilitating hematologic diseases which may behave in a relatively indolent fashion such as paroxysmal nocturnal hemoglobinuria PNH and refractory anemia RA or refractory anemia with ringed sideroblasts RARS However the 30 risk of treatment-related mortality TRM with standard myeloablative allotransplantation usually precludes these patients from potentially curative therapy because of concerns about shortening life in patients with these disorders In this protocol we investigate non-myeloablative allogeneic peripheral blood stem cell PBSC transplantation in two groups of subjects where standard allogeneic transplantation is considered to have unacceptable toxicity
Group A Subjects with hematologic malignancies with factors putting them at high risk for transplant related complications and mortality including prior intensive chemo-radiotherapy and co-morbid diseases
Group B Subjects with hematologic diseases both clonal and non-clonal associated with reasonable longevity not currently considered for allogeneic BMT because of prohibitive procedural mortality with conventional BMT enrollment closed October 2010
In this protocol eligible subjects are treated with an allogeneic PBSC transplant from an HLA identical or single HLA antigen-mismatched family donor using an intensive immunosuppressive regimen without myeloablation in an attempt to decrease the transplant related toxicities while preserving the anti-malignancy andor anti-host marrow effect of the graft The low intensity non-myeloablative conditioning regimen should provide adequate immunosuppression to allow stem cell and lymphocyte engraftment T-cell replete donor-derived granulocyte colony stimulating factor G-CSF-mobilized PBSCs will be used to establish hematopoietic and lymphoid reconstitution We will add back lymphocytes in recipients with less than 100 donor T-cell chimerism in an attempt to prevent graft rejection and enhance a graft-versus-malignancy effect
The primary endpoint of this study is transplant related mortality 200 day survival Other end points include engraftment degree of donor-host chimerism incidence of acute and chronic graft versus host disease GVHD transplant related morbidity as well as disease-free and overall survival
The assumption that successful allogeneic BMT relies on the myeloablative effect of intensive but hazardous chemo-radiotherapy has largely restricted this therapeutic modality to patients with malignant or life-threatening hematologic disorders under the age of 55 years Treatment-related mortality increases substantially with age prior intensive treatment with chemo-radiotherapy worsening performance status and co-morbid medical conditions An unacceptable risk of death from conventional BMT renders many patients ineligible for what may otherwise be curative therapy
Several in vitro studies have demonstrated the existence of donor-derived CD4 and CD8 positive lymphocytes with specific reactivity for the patient s leukemia These cells provide a potent graft-versus-leukemia GVL effect This GVL effect is best seen in patients with CML relapsing after BMT where a single infusion of donor lymphocytes has been shown to induce complete remission In addition to the potent anti-leukemia effect of these cells there is now strong evidence that donor T-cells are capable of completely eradicating residual host hematopoietic cells in a non-myeloablative transplant setting graft-versus-marrow leading to successful and complete donor hematopoietic engraftment
Non-myeloablative allogenic peripheral blood stem cell transplants are currently being investigated in phase III trials assessing engraftment efficacy and toxicity at a number of transplant centers Preliminary data including our own experience with greater than 150 patients undergoing this type of procedure have shown a high rate of complete donor engraftment with a low toxicity profile Two recent studies investigating non-myeloablative allo-transplantation in standard risk patients revealed an extremely low rate of transplant-related complications and mortality
The decreased risk of transplant-related complications associated with non-myeloablative transplants expands the eligibility of transplant candidates as well as opens the possibility to evaluate non-myeloablative regimens in patients at high risk for complications with standard transplantation Besides hematologic malignancies allogeneic BMT has been shown to be curative in a number of debilitating hematologic diseases which may behave in a relatively indolent fashion such as paroxysmal nocturnal hemoglobinuria PNH and refractory anemia RA or refractory anemia with ringed sideroblasts RARS However the 30 risk of treatment-related mortality TRM with standard myeloablative allotransplantation usually precludes these patients from potentially curative therapy because of concerns about shortening life in patients with these disorders In this protocol we investigate non-myeloablative allogeneic peripheral blood stem cell PBSC transplantation in two groups of subjects where standard allogeneic transplantation is considered to have unacceptable toxicity
Group A Subjects with hematologic malignancies with factors putting them at high risk for transplant related complications and mortality including prior intensive chemo-radiotherapy and co-morbid diseases
Group B Subjects with hematologic diseases both clonal and non-clonal associated with reasonable longevity not currently considered for allogeneic BMT because of prohibitive procedural mortality with conventional BMT enrollment closed October 2010
In this protocol eligible subjects are treated with an allogeneic PBSC transplant from an HLA identical or single HLA antigen-mismatched family donor using an intensive immunosuppressive regimen without myeloablation in an attempt to decrease the transplant related toxicities while preserving the anti-malignancy andor anti-host marrow effect of the graft The low intensity non-myeloablative conditioning regimen should provide adequate immunosuppression to allow stem cell and lymphocyte engraftment T-cell replete donor-derived granulocyte colony stimulating factor G-CSF-mobilized PBSCs will be used to establish hematopoietic and lymphoid reconstitution We will add back lymphocytes in recipients with less than 100 donor T-cell chimerism in an attempt to prevent graft rejection and enhance a graft-versus-malignancy effect
The primary endpoint of this study is transplant related mortality 200 day survival Other end points include engraftment degree of donor-host chimerism incidence of acute and chronic graft versus host disease GVHD transplant related morbidity as well as disease-free and overall survival
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 99-H-0050 | None | None | None |