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| ID | Type | Description | Link |
|---|---|---|---|
| U01HL069294 | U.S. NIH Grant/Contract | View source | |
| 5U24CA076518 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Heart, Lung, and Blood Institute (NHLBI) | NIH |
| Blood and Marrow Transplant Clinical Trials Network | NETWORK |
| National Cancer Institute (NCI) | NIH |
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Bone marrow transplants are one treatment option for people with leukemia or lymphoma. Family members or unrelated donors with a similar type of bone marrow usually donate their bone marrow to the transplant patients. This study will evaluate the effectiveness of a new type of bone marrow transplant-one that uses lower doses of chemotherapy and bone marrow donated from family members with only partially matched bone marrow-in people with leukemia or lymphoma.
Leukemia and lymphoma are types of blood cancers. Chemotherapy is a common treatment option for people with these types of cancers, but if the cancer does not respond well to chemotherapy, or if the cancer returns, a bone marrow transplant is another treatment option. In a bone marrow transplant procedure, healthy bone marrow is taken from a donor and transplanted into the patient. Bone marrow can be donated by a family member or an unrelated donor who has a similar type of bone marrow. Most bone marrow transplants are performed using a donor who is a perfect or close-to-perfect tissue match. However, for participants in this study, researchers have determined that a completely matched donor is unavailable within participants' families, and an unrelated donor match has not been found either. Participants do, however, have a family member who is a partial tissue match. Typically, people who are undergoing a bone marrow transplant receive high doses of chemotherapy before the transplant to prepare their bodies to accept the donor bone marrow. In this study, participants will undergo a new type of bone marrow transplant called a nonmyeloablative transplant, which is a reduced intensity method of transplantation that does not require high doses of chemotherapy. The purpose of the study is to examine the safety and effectiveness of a nonmyeloablative bone marrow transplant that uses partially matched bone marrow donated by a family member as a treatment option for people with leukemia or lymphoma.
This study will enroll people with leukemia or lymphoma who have a family member with a partial tissue match. Participants will be admitted to the hospital and will first receive a type of chemotherapy called fludarabine, which will be given intravenously for 5 days. In addition, another type of chemotherapy, cyclophosphamide, will be given intravenously on the first and second day. After 5 days, participants will receive a small dose of radiation. The next day, participants will undergo the bone marrow transplant. The third and fourth day after the transplant, participants will receive high doses of cyclophosphamide to help prevent two complications, graft rejection, which occurs when the body's immune system rejects the donor bone marrow, and graft-versus-host disease (GVHD), which is an attack by the donor cells on the body's normal tissues. On the fifth day after the transplant, participants will receive two additional medications, tacrolimus and mycophenolate mofetil (MMF), to help prevent GVHD; some participants may receive cyclosporine instead of tacrolimus. Participants will receive MMF for about 5 weeks and tacrolimus for about 6 months. Also beginning on the fifth day after the transplant, participants will receive daily injections of a growth factor called granulocyte-colony stimulating factor (G-CSF), which is a natural protein that increases the white blood cell count; G-CSF will be continued until a participant's white blood cell count is normal again.
Participants will remain in the hospital for approximately 2 to 3 months, but possibly longer if there are complications. While participants are in the hospital, blood samples will be collected regularly to evaluate the response and possible side effects to treatment, including GVHD. If necessary, participants will receive platelet and red blood cell transfusions. Follow-up study visits will occur 6 months and 1 year after the transplant. At Months 1, 2, 6, and 12 after the transplant, blood or bone marrow samples will be obtained. Study researchers will keep track of participants' medical condition through phone calls or mailings to participants and their doctors once a year for the rest of the participants' lives.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Haploidentical Bone Marrow Transplant | Experimental | Participants will receive a human leucocyte antigen (HLA) haploidentical bone marrow transplantation using a non-myeloablative preparative regimen, GVHD prophylaxis. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Haploidentical Bone Marrow Transplantation | Biological | The transplant preparative regimen is listed below. The - sign is the number of days before the transplant.
Day 0 is the day of the infusion of non-T-cell depleted bone marrow. The bone marrow will be obtained from haploidentical related donor. |
| Measure | Description | Time Frame |
|---|---|---|
| Overall Survival at 180 Days From the Time of Transplant | Measured at Month 6 and Year 1 |
| Measure | Description | Time Frame |
|---|---|---|
| Neutrophil Recovery | Cumulative incidence of neutrophil recovery >500/μL at day +56 | Measured at Days 28, 56, 90, and 100 |
| Primary Graft Failure | Primary graft failure is defined as < 5% donor chimerism on all measurements. |
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Inclusion Criteria:
Participants must be 21 to 70 years old; participants 1 to 21 years old are also eligible if they are ineligible for BMT CTN #0501 (NCT00412360)
Donor must be at least 18 years of age
Human leucocyte antigen (HLA) typing will be performed at high resolution (allele level) for the HLA-A, -B, Cw, DRB1, and -DQB1 loci. A minimum match of 5/10 is required. An unrelated donor search is not required for a person to be eligible for this study if the clinical situation dictates an urgent transplant. Clinical urgency is defined as 6 to 8 weeks from referral to transplant center or low likelihood of finding a matched, unrelated donor. The donor and recipient must be identical, as determined by high resolution typing, on at least one allele of each of the following genetic loci: HLA-A, HLA-B, HLA-Cw, HLA-DRB1, and HLA-DQB1. Fulfillment of this criterion shall be considered sufficient evidence that the donor and recipient share one HLA haplotype, and typing of additional family members is not required.
Must have received cytotoxic chemotherapy within 3 months of the consent date (measured from the start date of chemotherapy)
Acute leukemias (includes T lymphoblastic lymphoma) in the second or subsequent complete remission (CR)
Burkitt's lymphoma in the second or subsequent CR
Lymphoma
Patients with adequate physical function as measured by the following:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Mary Horowitz, MD, MS | Center for International Blood and Marrow Transplant Research (CIBMTR), Medical College of Wisconsin | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| City of Hope National Medical Center | Duarte | California | 91010-3000 | United States | ||
| University of California San Diego Medical Center |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 21527516 | Result | Brunstein CG, Fuchs EJ, Carter SL, Karanes C, Costa LJ, Wu J, Devine SM, Wingard JR, Aljitawi OS, Cutler CS, Jagasia MH, Ballen KK, Eapen M, O'Donnell PV; Blood and Marrow Transplant Clinical Trials Network. Alternative donor transplantation after reduced intensity conditioning: results of parallel phase 2 trials using partially HLA-mismatched related bone marrow or unrelated double umbilical cord blood grafts. Blood. 2011 Jul 14;118(2):282-8. doi: 10.1182/blood-2011-03-344853. Epub 2011 Apr 28. | |
| 24862638 |
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Results will be published in a manuscript
Within 6 months of official study closure at participating sites.
Available to the public.
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| ID | Title | Description |
|---|---|---|
| FG000 | Haplo-marrow Transplantation | Haploidentical bone marrow transplantation using a non-myeloablative preparative regimen. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP_ICF | Yes | Yes | Yes | Study Protocol, Statistical Analysis Plan, and Informed Consent Form | Jan 28, 2009 |
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| National Marrow Donor Program |
| OTHER |
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|
| GVHD prophylaxis | Biological | The GVHD prophylaxis regimen will consist of the following:
|
|
| Measured at Day 67 |
| Secondary Graft Failure | Secondary graft failure is defined as initial recovery followed by neutropenia with < 5% donor chimerism. If no chimerism assays were performed and absolute neutrophil count is < 500/mm3, then it will be counted as a secondary graft failure. | Measured at Day 100 |
| Platelet Recovery | Platelet Recovery to 20K | Measured at Days 56, 90, and 100 |
| Platelet Recovery | Platelet Recovery to 50K | Measured at Days 56, 90, and 100 |
| Donor Cell Engraftment | Marrow or Blood Sample. Donor cell engraftment is defined as donor chimerism ≥ 5% on Day ≥ 56 after transplantation. Chimerism should be evaluated on Days ~28, ~56, ~180, and ~365 after transplantation. Chimerism may be evaluated in whole blood or mononuclear fraction. | Measured at Day 56 |
| Acute Graft-versus-host Disease (GVHD) | Measured at Day 100 |
| Chronic GVHD | Measured at Year 1 |
| Progression-free Survival | Progression-free survival is defined as the minimum time interval of the times to relapse/recurrence, to death or to last follow-up. | Measured at Year 1 |
| Treatment-related Mortality (TRM) | Measured at 6 months and 1 year |
| Infections | Number of infections; infections will be reported by anatomic site, date of onset, organism and resolution, if any. Patients will be followed for infection for 1 year post-transplant. | Measured at Year 1 |
| La Jolla |
| California |
| 92093 |
| United States |
| University of Florida College of Medicine (Shands) | Gainesville | Florida | 32610-0277 | United States |
| Bone Marrow Transplant Group of Georgia, Northside Hospital | Atlanta | Georgia | 30342 | United States |
| Kapi'olani Medical Center for Women and Children, University of Hawaii | Honolulu | Hawaii | 96826 | United States |
| University of Maryland, Greenbaum Cancer Center | Baltimore | Maryland | 21201 | United States |
| Johns Hopkins University/Sidney Kimmel Comprehensive Cancer Center (SKCCC) | Baltimore | Maryland | 21231 | United States |
| DFCI, Massachusetts General Hospital | Boston | Massachusetts | 02114 | United States |
| Karmanos Cancer Institute, Children's Hospital of Michigan | Detroit | Michigan | 48201 | United States |
| Washington University, Barnes Jewish Hospital | St Louis | Missouri | 63110 | United States |
| Oregon Health & Science University | Portland | Oregon | 97239-3098 | United States |
| Fox Chase, Temple University | Philadelphia | Pennsylvania | 19111-2442 | United States |
| Medical University of South Carolina | Charleston | South Carolina | 29425 | United States |
| Vanderbilt University Medical Center | Nashville | Tennessee | 37232-8210 | United States |
| Baylor University Medical Center | Dallas | Texas | 75246 | United States |
| Texas Transplant Institute | San Antonio | Texas | 78229 | United States |
| Fred Hutchinson Cancer Research Center | Seattle | Washington | 98109-1024 | United States |
| Result |
| Eapen M, O'Donnell P, Brunstein CG, Wu J, Barowski K, Mendizabal A, Fuchs EJ. Mismatched related and unrelated donors for allogeneic hematopoietic cell transplantation for adults with hematologic malignancies. Biol Blood Marrow Transplant. 2014 Oct;20(10):1485-92. doi: 10.1016/j.bbmt.2014.05.015. Epub 2014 May 23. |
| COMPLETED |
|
| NOT COMPLETED |
|
|
Received transplant.
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| ID | Title | Description |
|---|---|---|
| BG000 | Haplo-marrow Transplantation | Haploidentical bone marrow transplantation using a non-myeloablative preparative regimen. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | |||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| ||||||||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| |||||||||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| |||||||||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
| |||||||||||||||||||||||
| Karnofsky Performance-status score | Assesses patient self-perceived global quality of life and functioning (excellent, very good, good, fair, poor), where 100 equals perfect quality of life. | Number | participants |
| ||||||||||||||||||||||
| Primary Disease | Number | participants |
| |||||||||||||||||||||||
| Human leucocyte antigen (HLA) Typing Match Score - GVH direction | HLA typing will be performed at high resolution (allele level) for the HLA-A, -B, Cw, DRB1, and -DQB1 loci. A minimum match of 5/10 is required. | Number | participants |
| ||||||||||||||||||||||
| HLA Typing Match Score - Host vs Graft (HVG) direction | HLA typing will be performed at high resolution (allele level) for the HLA-A, -B, Cw, DRB1, and -DQB1 loci. A minimum match of 5/10 is required. | Number | participants |
| ||||||||||||||||||||||
| Weight | Median | Full Range | kilograms |
|
| 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 | Overall Survival at 180 Days From the Time of Transplant | Posted | Number | 95% Confidence Interval | percentage of participants | Measured at Month 6 and Year 1 |
|
|
| ||||||||||||||||||||||||||||||||||
| Secondary | Neutrophil Recovery | Cumulative incidence of neutrophil recovery >500/μL at day +56 | Posted | Number | 95% Confidence Interval | percentage of participants | Measured at Days 28, 56, 90, and 100 |
|
|
| |||||||||||||||||||||||||||||||||
| Secondary | Primary Graft Failure | Primary graft failure is defined as < 5% donor chimerism on all measurements. | Posted | Number | participants | Measured at Day 67 |
|
|
| ||||||||||||||||||||||||||||||||||
| Secondary | Secondary Graft Failure | Secondary graft failure is defined as initial recovery followed by neutropenia with < 5% donor chimerism. If no chimerism assays were performed and absolute neutrophil count is < 500/mm3, then it will be counted as a secondary graft failure. | Posted | Number | participants | Measured at Day 100 |
|
| |||||||||||||||||||||||||||||||||||
| Secondary | Platelet Recovery | Platelet Recovery to 20K | Posted | Number | 95% Confidence Interval | percentage of participants | Measured at Days 56, 90, and 100 |
|
|
| |||||||||||||||||||||||||||||||||
| Secondary | Platelet Recovery | Platelet Recovery to 50K | Posted | Number | 95% Confidence Interval | percentage of participants | Measured at Days 56, 90, and 100 |
|
|
| |||||||||||||||||||||||||||||||||
| Secondary | Donor Cell Engraftment | Marrow or Blood Sample. Donor cell engraftment is defined as donor chimerism ≥ 5% on Day ≥ 56 after transplantation. Chimerism should be evaluated on Days ~28, ~56, ~180, and ~365 after transplantation. Chimerism may be evaluated in whole blood or mononuclear fraction. | Posted | Number | participants | Measured at Day 56 |
|
| |||||||||||||||||||||||||||||||||||
| Secondary | Acute Graft-versus-host Disease (GVHD) | Posted | Number | 95% Confidence Interval | percentage of participants | Measured at Day 100 |
|
|
| ||||||||||||||||||||||||||||||||||
| Secondary | Chronic GVHD | Posted | Number | 95% Confidence Interval | percentage of participants | Measured at Year 1 |
|
|
| ||||||||||||||||||||||||||||||||||
| Secondary | Progression-free Survival | Progression-free survival is defined as the minimum time interval of the times to relapse/recurrence, to death or to last follow-up. | Posted | Number | 95% Confidence Interval | percentage of participants | Measured at Year 1 |
|
| ||||||||||||||||||||||||||||||||||
| Secondary | Treatment-related Mortality (TRM) | Posted | Number | 95% Confidence Interval | percentage of participants | Measured at 6 months and 1 year |
|
|
| ||||||||||||||||||||||||||||||||||
| Secondary | Infections | Number of infections; infections will be reported by anatomic site, date of onset, organism and resolution, if any. Patients will be followed for infection for 1 year post-transplant. | 36 patients incurred a total number of 108 infection events. | Posted | Number | participants | Measured at Year 1 |
|
|
1-year post-transplant
Serious adverse events are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event.
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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 | Haplo-marrow Transplantation | Haploidentical bone marrow transplantation using a non-myeloablative preparative regimen. | 5 | 52 | 1 | 52 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Atrial fibrillation | Cardiac disorders | MedDRA v12.0 | Non-systematic Assessment |
| |
| Cardiac failure congestive | Cardiac disorders | MedDRA v12.0 | Non-systematic Assessment |
| |
| Pseudomonas infection | Infections and infestations | MedDRA v12.0 | Non-systematic Assessment |
| |
| Respiratory distress | Respiratory, thoracic and mediastinal disorders | MedDRA v12.0 | Non-systematic Assessment |
| |
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA v12.0 | Non-systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Headache | Nervous system disorders | MedDRA v12.0 | Non-systematic Assessment |
|
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Adam Mendizabal | The EMMES Corporation | 301-251-1161 | amendizabal@EMMES.com |
| Nov 29, 2022 |
| Prot_SAP_ICF_000.pdf |
| ID | Term |
|---|---|
| D015452 | Precursor B-Cell Lymphoblastic Leukemia-Lymphoma |
| D015470 | Leukemia, Myeloid, Acute |
| D002051 | Burkitt Lymphoma |
| D016393 | Lymphoma, B-Cell |
| D008224 | Lymphoma, Follicular |
| D016403 | Lymphoma, Large B-Cell, Diffuse |
| D054198 | Precursor Cell Lymphoblastic Leukemia-Lymphoma |
| ID | Term |
|---|---|
| D007945 | Leukemia, Lymphoid |
| D007938 | Leukemia |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| D007951 | Leukemia, Myeloid |
| D020031 | Epstein-Barr Virus Infections |
| D006566 | Herpesviridae Infections |
| D004266 | DNA Virus Infections |
| D014777 | Virus Diseases |
| D007239 | Infections |
| D014412 | Tumor Virus Infections |
| D008228 | Lymphoma, Non-Hodgkin |
| D008223 | Lymphoma |
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| Unknown or Not Reported |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| 80% |
|
| 70% |
|
| Biphenotypic/Undifferentiated Leukemia |
|
| Hodgkins Lymphoma |
|
| Large Cell Lymphoma |
|
| Marginal Zone B-cell Lymphoma |
|
| Mantle Cell Lymphoma |
|
| 7/10 |
|
| 8/10 |
|
| 7/10 |
|
| 8/10 |
|
| 9/10 |
|
| 10/10 |
|
| Categories |
|---|
| Day 28 |
| |||||
| Day 56 |
| |||||
| Day 90 |
| |||||
| Day 100 |
|
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| Title | Denominators | Categories | ||||
|---|---|---|---|---|---|---|
|
| Day 56 |
| |||||
| Day 90 |
| |||||
| Day 100 |
|
| Day 56 |
| |||||
| Day 90 |
| |||||
| Day 100 |
|
| Title | Denominators | Categories | ||||
|---|---|---|---|---|---|---|
| Chimerism Performed |
| |||||
| Donor Percentage ≥95% |
| |||||
| Donor Percentage 5%-95% |
| |||||
| Donor Percentage <5% |
|
|
| Grade III-IV Acute GVHD |
|
|
| Title |
|---|
| Denominators |
|---|
| Categories |
|---|
|
|
| 1 year |
|
| Title | Denominators | Categories | ||||
|---|---|---|---|---|---|---|
| 1 Infection |
| |||||
| 2 Infections |
| |||||
| 3 Infections |
| |||||
| 4 Infections |
| |||||
| 5 Infections |
| |||||
| 6-10 Infections |
| |||||
| >10 Infections |
|