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The central hypothesis of this study is that use of a less toxic chemotherapy preparative regimen for allogeneic hematopoietic stem cell transplantation in combination with T cell depletion with alemtuzumab for patients with high risk hematologic malignancies will allow effective control of disease and improved disease free and overall survival compared with historical expectations. Specifically, the objectives are to estimate toxicity, disease free, progression free, event free, and overall survival rates in patients treated with alemtuzumab T cell depleted, reduced intensity preparative regimen followed by allogeneic hematopoietic transplantation; evaluate immune recovery following this reduced intensity allogeneic immunotherapy; develop an in vitro assay to allow patient individualized targeted dosing.
The central hypothesis of this study is that use of a less toxic chemotherapy preparative regimen for allogeneic hematopoietic stem cell transplantation in combination with T cell depletion with alemtuzumab for patients with high risk hematologic malignancies will allow effective control of disease and improved disease free and overall survival compared with historical expectations. Specifically, the objectives are to estimate toxicity, disease free, progression free, event free and overall survival rates in patients treated with an alemtuzumab T cell depleted, reduced intensity preparative regimen followed by allogeneic hematopoietic transplantation; evaluate immune recovery following this reduced intensity allogeneic immunotherapy; develop an in vitro assay to allow patient individualized targeted dosing. The study population is HIV negative, adult patients who are not pregnant but have confirmed diagnosis of disease; must have Cancer and Leukemia Group B (CALGB) performance status (PS) 0, 1, or 2; must have a 3-6/6 human leukocyte antigen (HLA)-matched related donor or 8/8 (A, B, C, DRB1, DQ are the primary determinants) or better HLA-matched unrelated donor who is evaluated and deemed able to provide peripheral blood stem cells (PBPCs) and/or marrow by the transplant team. The target population of patients is those with a high chance of progressive lymphoid or myelomatous diseases, progressive myeloid diseases, marrow failure syndromes or myeloproliferative disorders.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort A - Lymphoid Disease | Experimental | Group A: Patients with a high chance of progressive lymphoid or myelomatous disease undergo Non-myeloablative Stem Cell Transplantation. |
|
| Cohort B - Myeloid Disease | Experimental | Group B: Patients with a high chance of progressive myeloid diseases, marrow failure syndromes or myeloproliferative disorders undergo Non-myeloablative Stem Cell Transplantation. |
|
| Donor | No Intervention | Donor priming and apheresis will include filgrastim 8 mcg/kg subcutaneously twice daily for 4 days prior to stem cell collection and continuing until pheresis is completed. Alternative mobilization strategies may be employed at the investigator's discretion. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Non-myeloablative Stem Cell Transplantation | Drug | The preparative regimen is 4 days of daily fludarabine at 40 mg/m2/d infused over 30 minutes; melphalan 140 mg/m2/d for 1 day administered over 15 minutes; 4 days of Alemtuzumab at 20 mg/d in 250 ml of normal saline infused over 3 hours. Group B's prep regimen will begin on day -5 or day -4 and busulfan 130mg/m2/d for 2 days over 3 hours. The peripheral blood stem cells (PBSCs) will be infused over 2-4 days. Patient evaluations will occur 2 times per week by physical exam for toxicity through day 45. |
| Measure | Description | Time Frame |
|---|---|---|
| Disease Free Survival | Estimate disease free survival rates in participants treated with an alemtuzumab T cell depleted, reduced intensity preparative regimen followed by allogeneic hematopoietic transplantation. Disease-free survival (DFS), progression-free survival (PFS), and overall survival (OS) rates after SCT were estimated using the Kaplan-Meier method. We performed univariate comparisons by using the log-rank test. DFS was defined as the period of time between the day of transplantation and either disease relapse or death due to the disease. The following variables were considered as confounders: recipient age, recipient sex, disease (myeloid or lymphoid), disease risk (standard or high), and donor type (MRD, MUD, or HAPLO donor). The percentage of participants who were disease free at 2 years is reported by donor type. | 2 years |
| Measure | Description | Time Frame |
|---|---|---|
| Immune Recovery | Evaluate immune recovery following this reduced intensity allogeneic immunotherapy. Quantification of CD3+, CD4+, and CD8+ T cells was performed by flow cytometry on fresh peripheral blood at approximately 1 month before transplantation and then 1.5, 3, 6, and 12 months after transplantation. The immune recovery rates of the CD3+, CD4+, and CD8+ T cells in the MRD, MUD, and HAPLO groups were compared by performing an analysis of variance at each time point after transplantation. The median T cell counts at 12 months for each type of cell are reported by donor type. |
| Measure | Description | Time Frame |
|---|---|---|
| Graft Versus Host Disease | Estimate toxicity including graft-versus-host disease (GVHD) in participants treated with an alemtuzumab T cell depleted, reduced intensity preparative regimen followed by allogeneic hematopoietic transplantation. Bone marrow aspiration and/or biopsy were performed 3-5 weeks after transplant to assess donor-cell engraftment. Acute or chronic GVHD was diagnosed and graded according to standard criteria. Toxicity was formally graded using the National Cancer Institute Common Toxicity Criteria version 3.0. |
Recipient Inclusion Criteria:
Subjects must have their diagnosis confirmed at the transplant center.
Performance status must be Cancer and Leukemia Group B (CALGB) = 0, 1, or 2.
Subjects must have a 3-6/6 human leukocyte antigen (HLA)-matched related donor or 8/8 or better allele level match matched unrelated donor (MUD) (at A,B, C, DRB1, DQ).
HIV negative.
Women of child bearing potential must have a negative pregnancy test within 1 week of starting therapy.
Subjects > or equal to 18 years of age are eligible.
Subjects must have a Multi Gated Acquisition Scan (MUGA) and/or Echocardiography (ECHO) or cardiac magnetic resonance (MR) and or diffusing capacity testing of the lung for carbon monoxide (DLCO) performed before transplant.
Specific populations:
Recipient Exclusion Criteria:
Donor Inclusion Criteria:
Donor must be capable of providing informed consent. If 14-17 years of age, a 'single patient exemption' from the local Institutional Review Board must be obtained.
Donor must not have any medical condition which would make mobilization or apheresis more than a minimal risk, and should have the following:
Females should not be pregnant or lactating and have a negative serum pregnancy test within 1 week of beginning mobilization if of child bearing potential.
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| Name | Affiliation | Role |
|---|---|---|
| David Rizzieri, MD | Duke Health | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Duke University Health System | Durham | North Carolina | 27710 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 24269380 | Result | Kanda J, Long GD, Gasparetto C, Horwitz ME, Sullivan KM, Chute JP, Morris A, Shafique M, Li Z, Chao NJ, Rizzieri DA. Reduced-intensity allogeneic transplantation using alemtuzumab from HLA-matched related, unrelated, or haploidentical related donors for patients with hematologic malignancies. Biol Blood Marrow Transplant. 2014 Feb;20(2):257-63. doi: 10.1016/j.bbmt.2013.11.010. Epub 2013 Nov 20. |
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Recipients had history and exam, labs, x-ray, and possible bone marrow aspirate. Radiation therapy may be used prior to transplant for minimal active disease. Donor selection included a 5-6/6 matched sibling as the first choice, a matched unrelated donor as the second choice, or a 3-5/6 partially matched family member as the third choice.
170 transplant recipients were recruited through the Adult Bone Marrow Transplant Program at Duke University Medical Center. Recruitment began in February, 2008 and ended in June, 2013. 33 recipients were screen failures. 94 donors were consented for leukapheresis.
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| ID | Title | Description |
|---|---|---|
| FG000 | Cohort A - Lymphoid Disease | Non-myeloablative stem cell transplant (SCT): Donor will receive Granulocyte colony-stimulating factor (G-CSF) 8 mcg/kg/d subcutaneously twice daily for 4 days, until pheresis is completed or until white blood cells > 100,000. Recipients will be premedicated with Benadryl 50 mg intravenously (IV) or orally (PO), and acetaminophen 650 mg PO (or hydrocortisone 50-100 mg IV on first day). The preparative regimen is 4 days of daily fludarabine at 40 mg/m2/d infused over 30 minutes; melphalan 140 mg/m2/d for 1 day administered over 15 minutes; 4 days of Alemtuzumab at 20 mg/d in 250 ml of normal saline infused over 3 hours. The PBSCs will be infused over 2-4 days. Participant evaluations will occur 2 times per week by physical exam for toxicity through day 45. |
| FG001 | Cohort B - Myeloid Disease | Non-myeloablative stem cell transplant (SCT): Donor will receive granulocyte colony stimulating factor (G-CSF) 8 mcg/kg/d subcutaneously twice daily for 4 days, until pheresis is completed or until white blood cells > 100,000. Recipients will be premedicated with Benadryl 50 mg intravenously (IV) or orally (PO), and acetaminophen 650 mg PO (or hydrocortisone 50-100 mg IV on first day). The preparative regimen is 4 days of daily fludarabine at 40 mg/m2/d infused over 30 minutes; melphalan 140 mg/m2/d for 1 day administered over 15 minutes; 4 days of Alemtuzumab at 20 mg/d in 250 ml of normal saline infused over 3 hours. The prep regimen will begin on day -5 or day -4 and busulfan 130mg/m2/d for 2 days over 3 hours. The PBSCs will be infused over 2-4 days. Participant evaluations will occur 2 times per week by physical exam for toxicity through day 45. |
| FG002 | Donor |
Multiple choices for 3-5/6 human leukocyte antigen (HLA) matched family member donors order of choice will be best match, then cytomegalovirus (CMV) negativity, then Killer-cell immunoglobulin-like receptors (KIR) mismatching (for natural killer [NK] cell activity), then history of pregnancy. All subjects without an available matched sibling must have a donor search initiated with the national bank. If potential high resolution matches are found but not utilized, the reason for proceeding with a partially matched family member should be documented (i.e. donor not available, not enough time to allow MUD donor work up and collection due to high risk nature of the subject's disease, etc). |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Participants who proceeded to therapy and transplant.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Cohort A - Lymphoid Disease | Non-myeloablative stem cell transplant (SCT): Donor will receive Granulocyte colony-stimulating factor (G-CSF) 8 mcg/kg/d subcutaneously twice daily for 4 days, until pheresis is completed or until white blood cells > 100,000. Recipients will be premedicated with Benadryl 50 mg intravenously (IV) or orally (PO), and acetaminophen 650 mg PO (or hydrocortisone 50-100 mg IV on first day). The preparative regimen is 4 days of daily fludarabine at 40 mg/m2/d infused over 30 minutes; melphalan 140 mg/m2/d for 1 day administered over 15 minutes; 4 days of Alemtuzumab at 20 mg/d in 250 ml of normal saline infused over 3 hours. The PBSCs will be infused over 2-4 days. Participant evaluations will occur 2 times per week by physical exam for toxicity through day 45. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Disease Free Survival | Estimate disease free survival rates in participants treated with an alemtuzumab T cell depleted, reduced intensity preparative regimen followed by allogeneic hematopoietic transplantation. Disease-free survival (DFS), progression-free survival (PFS), and overall survival (OS) rates after SCT were estimated using the Kaplan-Meier method. We performed univariate comparisons by using the log-rank test. DFS was defined as the period of time between the day of transplantation and either disease relapse or death due to the disease. The following variables were considered as confounders: recipient age, recipient sex, disease (myeloid or lymphoid), disease risk (standard or high), and donor type (MRD, MUD, or HAPLO donor). The percentage of participants who were disease free at 2 years is reported by donor type. | All subjects with complete response. Cohort A (n=62) had acute or chronic leukemia (ALL or CLL), lymphoma, or myeloma. Cohort B (n=62) had acute or chronic myeloid leukemia (AML or CML), myelodysplastic disorder or myeloproliferative disorder. DFS was analyzed by type of donor (Matched Unrelated Donor; Matched Related Donor; Haplo-identical). | Posted | Number | 95% Confidence Interval | percentage of participants | 2 years |
Participants will be evaluated at a minimum of 2 times per week by physical exam for toxicity following Version 3 of the NCI expanded common toxicity criteria through day 45 following the first infusion.
Graft versus Host Disease (GVHD) and other toxicity was graded per NCI's common terminology criteria for adverse events (CTCAE) (3.0).
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Cohort A - Lymphoid Disease | Non-myeloablative stem cell transplant (SCT): Donor will receive Granulocyte colony-stimulating factor (G-CSF) 8 mcg/kg/d subcutaneously twice daily for 4 days, until pheresis is completed or until white blood cells > 100,000. Recipients will be premedicated with Benadryl 50 mg intravenously (IV) or orally (PO), and acetaminophen 650 mg PO (or hydrocortisone 50-100 mg IV on first day). The preparative regimen is 4 days of daily fludarabine at 40 mg/m2/d infused over 30 minutes; melphalan 140 mg/m2/d for 1 day administered over 15 minutes; 4 days of Alemtuzumab at 20 mg/d in 250 ml of normal saline infused over 3 hours. The peripheral blood stem cells (PBSCs) will be infused over 2-4 days. Participant evaluations will occur 2 times per week by physical exam for toxicity through day 45. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Supraventricular and nodal arrhythmia | Cardiac disorders | CTCAE (3.0) | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Failure to Engraft | Blood and lymphatic system disorders | CTCAE (3.0) | Non-systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| David Rizzieri, MD | Duke University Medical Center | 919-668-1040 | david.rizzieri@duke.edu |
Not provided
| ID | Term |
|---|---|
| D006689 | Hodgkin Disease |
| D008228 | Lymphoma, Non-Hodgkin |
| D054219 | Neoplasms, Plasma Cell |
| D007938 | Leukemia |
| D000754 | Anemia, Refractory, with Excess of Blasts |
| ID | Term |
|---|---|
| D008223 | Lymphoma |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D008232 | Lymphoproliferative Disorders |
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|
|
| 1 year |
| Progression Free Survival | Progression-free survival (PFS) rates after stem cell transplant were estimated using the Kaplan-Meier method. We performed univariate comparisons by using the log-rank test. PFS was defined as the period of time between the day of transplantation and either the day underlying disease progression was documented or death occurred by any cause. The following variables were considered as confounders: recipient age, recipient sex, disease (myeloid or lymphoid), disease risk (standard or high), and donor type (MRD, MUD, or HAPLO donor). The percentage of participants progression free at 2 years is reported by donor type. Progression = > 25% increase of serum M-protein and/or urine M-protein. Also, an absolute increase in bone marrow plasma cells > 10%, new bone lesions or soft tissue plasmacytomas or increase in the size of existing bone lesions or soft tissue plasmacytomas or development of hypercalcemia that can be attributed solely to the plasma cell proliferative disorder. | 2 years |
| Overall Survival | Estimate overall survival rates in participants treated with an alemtuzumab T cell depleted, reduced intensity preparative regimen followed by allogeneic hematopoietic transplantation. Disease-free survival (DFS), progression-free survival (PFS), and overall survival (OS) rates after SCT were estimated using the Kaplan-Meier method. We performed univariate comparisons by using the log-rank test. OS was defined as the period of time between the day of transplantation and death. The following variables were considered as confounders: recipient age, recipient sex, disease (myeloid or lymphoid), disease risk (standard or high), and donor type (MRD, MUD, or HAPLO donor). The percentage of participants surviving 2 years by donor type is reported. | 2 years |
| Graft Failure | Estimate toxicity including graft-versus-host disease (GVHD) in participants treated with an alemtuzumab T cell depleted, reduced intensity preparative regimen followed by allogeneic hematopoietic transplantation. Bone marrow aspiration and/or biopsy were performed 3-5 weeks after transplant to assess donor-cell engraftment. Primary Graft Failure was defined as a neutrophil count below 500/μL or the absence of donor-derived hematopoiesis (<5%donor cells) before relapse, death, or re-transplantation. Secondary Graft Failure was defined as the achievement of primary engraftment and a subsequent decrease in neutrophils to 3 consecutive counts of less than 100/μL or the absence of donor-derived hematopoiesis (<5% donor cells) before relapse, death, or re-transplantation. | 180 days |
| 180 days |
| BG001 | Cohort B - Myeloid Disease | Non-myeloablative stem cell transplant (SCT): Donor will receive granulocyte colony stimulating factor (G-CSF) 8 mcg/kg/d subcutaneously twice daily for 4 days, until pheresis is completed or until white blood cells > 100,000. Recipients will be premedicated with Benadryl 50 mg intravenously (IV) or orally (PO), and acetaminophen 650 mg PO (or hydrocortisone 50-100 mg IV on first day). The preparative regimen is 4 days of daily fludarabine at 40 mg/m2/d infused over 30 minutes; melphalan 140 mg/m2/d for 1 day administered over 15 minutes; 4 days of Alemtuzumab at 20 mg/d in 250 ml of normal saline infused over 3 hours. The prep regimen will begin on day -5 or day -4 and busulfan 130mg/m2/d for 2 days over 3 hours. The PBSCs will be infused over 2-4 days. Participant evaluations will occur 2 times per week by physical exam for toxicity through day 45. |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| ID | Title | Description |
|---|---|---|
| OG000 | Cohort A & B- Lymphoid & Myeloid Disease | Non-myeloablative Stem Cell Transplant (SCT): Donor will receive Granulocyte colony-stimulating factor (G-CSF) 8 mcg/kg/d subcutaneously twice daily for 4 days, until pheresis is completed or until white blood cells > 100,000. Recipients will be premedicated with Benadryl 50 mg intravenously (IV) or orally (PO), and acetaminophen 650 mg PO (or hydrocortisone 50-100 mg IV on first day). The preparative regimen is 4 days of daily fludarabine at 40 mg/m2/d infused over 30 minutes; melphalan 140 mg/m2/d for 1 day administered over 15 minutes; 4 days of Alemtuzumab at 20 mg/d in 250 ml of normal saline infused over 3 hours. The prep regimen for myeloid disease will begin on day -5 or day -4 and busulfan 130mg/m2/d for 2 days over 3 hours. The Peripheral Blood Stem Cells (PBSCs) will be infused over 2-4 days. Participant evaluations will occur 2 times per week by physical exam for toxicity through day 45. |
|
|
| Secondary | Immune Recovery | Evaluate immune recovery following this reduced intensity allogeneic immunotherapy. Quantification of CD3+, CD4+, and CD8+ T cells was performed by flow cytometry on fresh peripheral blood at approximately 1 month before transplantation and then 1.5, 3, 6, and 12 months after transplantation. The immune recovery rates of the CD3+, CD4+, and CD8+ T cells in the MRD, MUD, and HAPLO groups were compared by performing an analysis of variance at each time point after transplantation. The median T cell counts at 12 months for each type of cell are reported by donor type. | All subjects with complete response. Cohort A (n=62) had acute or chronic leukemia (ALL or CLL), lymphoma, or myeloma. Cohort B (n=62) had acute or chronic myeloid leukemia (AML or CML), myelodysplastic disorder or myeloproliferative disorder. Analysis by type of donor (Matched Unrelated Donor; Matched Related Donor; Haplo-identical). | Posted | Mean | Standard Deviation | T cells/μL | 1 year |
|
|
|
| Secondary | Progression Free Survival | Progression-free survival (PFS) rates after stem cell transplant were estimated using the Kaplan-Meier method. We performed univariate comparisons by using the log-rank test. PFS was defined as the period of time between the day of transplantation and either the day underlying disease progression was documented or death occurred by any cause. The following variables were considered as confounders: recipient age, recipient sex, disease (myeloid or lymphoid), disease risk (standard or high), and donor type (MRD, MUD, or HAPLO donor). The percentage of participants progression free at 2 years is reported by donor type. Progression = > 25% increase of serum M-protein and/or urine M-protein. Also, an absolute increase in bone marrow plasma cells > 10%, new bone lesions or soft tissue plasmacytomas or increase in the size of existing bone lesions or soft tissue plasmacytomas or development of hypercalcemia that can be attributed solely to the plasma cell proliferative disorder. | All participants who received transplant. Cohort A (n=62) had acute or chronic leukemia (ALL or CLL), lymphoma, or myeloma. Cohort B (n=62) had acute or chronic myeloid leukemia (AML or CML), myelodysplastic disorder or myeloproliferative disorder. Analysis by type of donor (Matched Unrelated Donor; Matched Related Donor; Haplo-identical). | Posted | Number | 95% Confidence Interval | percentage of participants | 2 years |
|
|
|
| Secondary | Overall Survival | Estimate overall survival rates in participants treated with an alemtuzumab T cell depleted, reduced intensity preparative regimen followed by allogeneic hematopoietic transplantation. Disease-free survival (DFS), progression-free survival (PFS), and overall survival (OS) rates after SCT were estimated using the Kaplan-Meier method. We performed univariate comparisons by using the log-rank test. OS was defined as the period of time between the day of transplantation and death. The following variables were considered as confounders: recipient age, recipient sex, disease (myeloid or lymphoid), disease risk (standard or high), and donor type (MRD, MUD, or HAPLO donor). The percentage of participants surviving 2 years by donor type is reported. | All participants who received transplant. Cohort A (n=62) had acute or chronic leukemia (ALL or CLL), lymphoma, or myeloma. Cohort B (n=62) had acute or chronic myeloid leukemia (AML or CML), myelodysplastic disorder or myeloproliferative disorder. Analysis by type of donor (Matched Unrelated Donor; Matched Related Donor; Haplo-identical). | Posted | Number | 95% Confidence Interval | percentage of participants | 2 years |
|
|
|
| Other Pre-specified | Graft Versus Host Disease | Estimate toxicity including graft-versus-host disease (GVHD) in participants treated with an alemtuzumab T cell depleted, reduced intensity preparative regimen followed by allogeneic hematopoietic transplantation. Bone marrow aspiration and/or biopsy were performed 3-5 weeks after transplant to assess donor-cell engraftment. Acute or chronic GVHD was diagnosed and graded according to standard criteria. Toxicity was formally graded using the National Cancer Institute Common Toxicity Criteria version 3.0. | All participants who received transplant. Cohort A (n=62) had acute or chronic leukemia (ALL or CLL), lymphoma, or myeloma. Cohort B (n=62) had acute or chronic myeloid leukemia (AML or CML), myelodysplastic disorder or myeloproliferative disorder. Analysis by occurrence of Graft versus Host Disease (GvHD) and Graft Failure and donor type. | Posted | Number | 95% Confidence Interval | percentage of participants | 180 days |
|
|
|
| Secondary | Graft Failure | Estimate toxicity including graft-versus-host disease (GVHD) in participants treated with an alemtuzumab T cell depleted, reduced intensity preparative regimen followed by allogeneic hematopoietic transplantation. Bone marrow aspiration and/or biopsy were performed 3-5 weeks after transplant to assess donor-cell engraftment. Primary Graft Failure was defined as a neutrophil count below 500/μL or the absence of donor-derived hematopoiesis (<5%donor cells) before relapse, death, or re-transplantation. Secondary Graft Failure was defined as the achievement of primary engraftment and a subsequent decrease in neutrophils to 3 consecutive counts of less than 100/μL or the absence of donor-derived hematopoiesis (<5% donor cells) before relapse, death, or re-transplantation. | All subjects who received transplant. Cohort A (n=62) had acute or chronic leukemia (ALL or CLL), lymphoma, or myeloma. Cohort B (n=62) had acute or chronic myeloid leukemia (AML or CML), myelodysplastic disorder or myeloproliferative disorder. Analysis by occurrence of Graft versus Host Disease (GvHD) and donor type. | Posted | Number | number of participants | 180 days |
|
|
|
| 16 |
| 80 |
| 77 |
| 80 |
| EG001 | Cohort B - Myeloid Disease | Non-myeloablative stem cell transplant (SCT): Donor will receive granulocyte colony stimulating factor (G-CSF) 8 mcg/kg/d subcutaneously twice daily for 4 days, until pheresis is completed or until white blood cells > 100,000. Recipients will be premedicated with Benadryl 50 mg intravenously (IV) or orally (PO), and acetaminophen 650 mg PO (or hydrocortisone 50-100 mg IV on first day). The preparative regimen is 4 days of daily fludarabine at 40 mg/m2/d infused over 30 minutes; melphalan 140 mg/m2/d for 1 day administered over 15 minutes; 4 days of Alemtuzumab at 20 mg/d in 250 ml of normal saline infused over 3 hours. The prep regimen will begin on day -5 or day -4 and busulfan 130mg/m2/d for 2 days over 3 hours. The peripheral blood stem cells (PBSCs) will be infused over 2-4 days. Participant evaluations will occur 2 times per week by physical exam for toxicity through day 45. | 10 | 57 | 52 | 57 |
| Cardiac Ischemia/Infarction | Cardiac disorders | CTCAE (3.0) | Non-systematic Assessment |
|
| Death - NOS | General disorders | CTCAE (3.0) | Non-systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | CTCAE (3.0) | Non-systematic Assessment |
|
| Nausea | Gastrointestinal disorders | CTCAE (3.0) | Non-systematic Assessment |
|
| Hepatobiliary/Pancreas | Hepatobiliary disorders | CTCAE (3.0) | Non-systematic Assessment | Elevation bilirubin and alkaline phosphate |
|
| Pancreatitis | Hepatobiliary disorders | CTCAE (3.0) | Non-systematic Assessment |
|
| Febrile neutropenia | Infections and infestations | CTCAE (3.0) | Non-systematic Assessment |
|
| Infection - Other | Infections and infestations | CTCAE (3.0) | Non-systematic Assessment | Meningitis; Parainfluenza; Herpes Zoster; Nocardia; Sepsis; Hickman line infection; C-Diff |
|
| Infection with Grade 3 or 4 neutrophils (ANC <1.0 x 10e9/L) | Infections and infestations | CTCAE (3.0) | Non-systematic Assessment | Sepsis; Parainfluenza III; Gram positive cocci (Staph Aureus); Human Herpes Virus 6; Pneumonia; Polyoma virus; Viremia |
|
| Infection with grade 3 or 4 neutrophils (ANC <1.0 x 10e9/L) | Infections and infestations | CTCAE (3.0) | Non-systematic Assessment | H. pylori; BK virus; Influenza |
|
| Infection with unknown ANC | Infections and infestations | CTCAE (3.0) | Non-systematic Assessment | Fever possibly due to Human Herpes Virus 6 |
|
| Altered Mental Status | Nervous system disorders | CTCAE (3.0) | Non-systematic Assessment |
|
| Adult Respiratory Distress Syndrome (ARDS) | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Non-systematic Assessment | Death |
|
| Cough | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Non-systematic Assessment |
|
| Dyspnea | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Non-systematic Assessment | Shortness of Breath |
|
| CNS - Cerebrovascular Ischemia | Nervous system disorders | CTCAE (3.0) | Non-systematic Assessment |
|
| Renal Failure | Renal and urinary disorders | CTCAE (3.0) | Non-systematic Assessment |
|
| Cystitis | Renal and urinary disorders | CTCAE (3.0) | Non-systematic Assessment |
|
| Hemorrhage | Vascular disorders | CTCAE (3.0) | Non-systematic Assessment | Central Nervous System |
|
| Liver dysfunction/failure | Hepatobiliary disorders | CTCAE (3.0) | Non-systematic Assessment | Portal hypertension |
|
| Diarrhea | Gastrointestinal disorders | CTCAE (3.0) | Non-systematic Assessment |
|
| Fever without neutropenia | General disorders | CTCAE (3.0) | Non-systematic Assessment |
|
| Rash/desquamation | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Non-systematic Assessment |
|
| Mucositis/Stomatitis | Gastrointestinal disorders | CTCAE (3.0) | Non-systematic Assessment |
|
| Nausea | Gastrointestinal disorders | CTCAE (3.0) | Non-systematic Assessment |
|
| Hemorrhage/Bleeding | Blood and lymphatic system disorders | CTCAE (3.0) | Non-systematic Assessment | Liver laceration; Retroperitoneal bleed; Ulcerative Colitis; Death (4) |
|
| Febrile neutropenia | Infections and infestations | CTCAE (3.0) | Non-systematic Assessment |
|
| Infection - Other | Infections and infestations | CTCAE (3.0) | Non-systematic Assessment | Pneumonia; Sepsis; Viremia; Human Herpes Virus 6; Herpes Simplex Virus; Cytomegalovirus; Fungal Pneumonia |
|
| Infection with Grade 3 or 4 neutrophils (ANC <1.0 x 10e9/L) | Infections and infestations | CTCAE (3.0) | Non-systematic Assessment | Bacteremia; Polyoma; Cytomegalovirus; Viremia; Varicella Zoster; Human Herpes Virus 6; Parainfluenza; Respiratory syncytial virus; Penicillium; Vancomycin-resistant enterococcus; Nocardia; Strep Viridans; Gram+ cocci; Ecoli; C-Diff; Klebsiella; MRSA |
|
| Infection with normal ANC or grade 1 or 2 neutrophils | Infections and infestations | CTCAE (3.0) | Non-systematic Assessment | Varicella Zoster; Cytomegalovirus; Viremia; Pneumonia; Stenotrophomonas Maltophilin; Herpes Simplex Virus; Human Herpes Virus 6; Gram+ cocci; Polyoma; Respiratory syncytial virus; C-Diff; Rhizopus; Parainfluenza; BK virus; Staph; MRSA; Gram- rod |
|
| Infection with unknown ANC | Infections and infestations | CTCAE (3.0) | Non-systematic Assessment | Thrush; Polyoma; Gram negative Sepsis; Gram positive cocci; Cytomegalovirus; Human Herpes Virus 6; Parainfluenza |
|
| Creatinine | Metabolism and nutrition disorders | CTCAE (3.0) | Non-systematic Assessment |
|
| Dyspnea | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Non-systematic Assessment | Shortness of Breath |
|
| Hypoxia | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Non-systematic Assessment |
|
| Renal/Genitourinary - Other | Renal and urinary disorders | CTCAE (3.0) | Non-systematic Assessment | Polyoma nephritis; Dysuria; Foscarnet urethritis; Hematuria; Renal Insufficiency; Renal Failure (3) |
|
Not provided
Not provided
Not provided
| D008206 |
| Lymphatic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| D006402 | Hematologic Diseases |
| D000753 | Anemia, Refractory |
| D000740 | Anemia |
| D009190 | Myelodysplastic Syndromes |
| D001855 | Bone Marrow Diseases |
|
| Matched Related Donors (MRD) n=38 - CD4+ Tcells/uL |
|
| Matched Unrelated Donors (MUD) n=53 -CD4+Tcells/uL |
|
| Haploidentical related (HAPLO) n=33 -CD4+Tcells/uL |
|
| Matched Related Donors (MRD) n=38 - CD8+ Tcells/uL |
|
| Matched Unrelated Donors (MUD) n=53 -CD8+Tcells/uL |
|
| Haploidentical related (HAPLO) n=33 -CD8+Tcells/uL |
|
|
|
|
| Grade III-IV GvHD (MRD n=38) |
|
| Grade III-IV GvHD (MUD=53) |
|
| Grade III-IV GvHD (HAPLO n=33) |
|
| Title | Measurements |
|---|---|
|