Efficacy Study of T Cell Depleted Allogeneic Non-myeloablative Stem Cell Transplant
![]() |
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
ClinicalTrials.gov Identifier: NCT00597714 |
Recruitment Status :
Completed
First Posted : January 18, 2008
Results First Posted : June 2, 2014
Last Update Posted : June 2, 2014
|
- Study Details
- Tabular View
- Study Results
- Disclaimer
- How to Read a Study Record
Condition or disease | Intervention/treatment | Phase |
---|---|---|
Hodgkin's Disease Non Hodgkin's Lymphoma Myeloma Leukemia Myelodysplasia | Drug: Non-myeloablative Stem Cell Transplantation | Phase 2 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 264 participants |
Allocation: | Non-Randomized |
Intervention Model: | Parallel Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | Efficacy Study of T Cell Depleted Allogeneic Non-myeloablative Stem Cell Transplantation |
Study Start Date : | February 2008 |
Actual Primary Completion Date : | July 2013 |
Actual Study Completion Date : | November 2013 |

Arm | Intervention/treatment |
---|---|
Experimental: Cohort A - Lymphoid Disease
Group A: Patients with a high chance of progressive lymphoid or myelomatous disease undergo Non-myeloablative Stem Cell Transplantation.
|
Drug: Non-myeloablative Stem Cell Transplantation
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.
Other Name: Allogeneic Stem Cell Transplant |
Experimental: Cohort B - Myeloid Disease
Group B: Patients with a high chance of progressive myeloid diseases, marrow failure syndromes or myeloproliferative disorders undergo Non-myeloablative Stem Cell Transplantation.
|
Drug: Non-myeloablative Stem Cell Transplantation
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.
Other Name: Allogeneic Stem Cell Transplant |
No Intervention: Donor
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.
|
- Disease Free Survival [ Time Frame: 2 years ]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.
- Immune Recovery [ Time Frame: 1 year ]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.
- Progression Free Survival [ Time Frame: 2 years ]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.
- Overall Survival [ Time Frame: 2 years ]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.
- Graft Failure [ Time Frame: 180 days ]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.
- Graft Versus Host Disease [ Time Frame: 180 days ]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.

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
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:
- Group A) Subjects with a high chance of progressive lymphoid or myelomatous diseases.
- Group B) Subjects with a high chance of progressive myeloid diseases, marrow failure syndromes or myeloproliferative disorders
Recipient Exclusion Criteria:
- Pregnant or lactating women.
- Subjects with other major medical or psychiatric illnesses which the treating physician feels could seriously compromise tolerance to this protocol.
- Subjects with uncontrolled, progressive infections.
- Subjects who are good candidates for long term disease control with standard chemotherapy or radiation or high dose therapy and autologous support.
- Subjects with active central nervous system (CNS) disease.
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:
- Adequate cardiac function by history and physical examination. Those with a history of cardiac failure or infarction should be evaluated by a cardiologist prior to donation
- Adequate hematopoietic function with hematocrit ≥ 30%, white blood cell count of 3000, and platelets 100,000.
- 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.

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00597714
United States, North Carolina | |
Duke University Health System | |
Durham, North Carolina, United States, 27710 |
Principal Investigator: | David Rizzieri, MD | Duke University Health System |
Responsible Party: | David Rizzieri, MD, Associate Professor of Medicine, Duke University |
ClinicalTrials.gov Identifier: | NCT00597714 |
Other Study ID Numbers: |
Pro00003567 |
First Posted: | January 18, 2008 Key Record Dates |
Results First Posted: | June 2, 2014 |
Last Update Posted: | June 2, 2014 |
Last Verified: | February 2014 |
Stem Cell Transplantation, Non-myeloablative |
Hodgkin Disease Preleukemia Myelodysplastic Syndromes Lymphoma Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders |
Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Bone Marrow Diseases Hematologic Diseases Precancerous Conditions |