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| ID | Type | Description | Link |
|---|---|---|---|
| P01CA015396 | U.S. NIH Grant/Contract | View source | |
| P30CA006973 | U.S. NIH Grant/Contract | View source | |
| JHOC-J0457 | Other Identifier | Johns Hopkins SKCCC | |
| JHOC-04072704 |
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| Name | Class |
|---|---|
| National Cancer Institute (NCI) | NIH |
RATIONALE: Giving low doses of chemotherapy, such as fludarabine and cyclophosphamide, and radiation therapy before a donor bone marrow transplant helps stop the growth of cancer cells. Giving chemotherapy or radiation therapy before or after transplant also stops the patient's immune system from rejecting the donor's bone marrow stem cells. The donated stem cells may replace the patient's immune system 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 tacrolimus and mycophenolate mofetil after the transplant may stop this from happening.
PURPOSE: This phase II trial is studying how well giving fludarabine and cyclophosphamide together with total-body irradiation works in treating patients who are undergoing a donor bone marrow transplant for hematologic cancer.
OBJECTIVES:
OUTLINE: This is a multicenter study. Patients are stratified according to risk of relapse (standard [defined as ≤ 30% risk] vs high [defined as ≥ 70% risk]).
Treatment continues in the absence of disease progression.
After completion of study transplantation, patients are followed on days 30, 60, 100, and 180; at 1 year; and then annually for 4 additional years.
PROJECTED ACCRUAL: A total of 75-100 patients will be accrued for this study within 3-4 years.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Mini-haplo Transplant | Experimental | Non-myeloablative haploidentical bone marrow transplant with a fludarabine, cyclophosphamide (Cy), TBI (total body irradiation) preparative regimen and post-transplant Cy, mycophenolate mofetil (MMF), and tacrolimus as GVHD prophylaxis. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| cyclophosphamide | Drug |
| ||
| fludarabine phosphate |
| Measure | Description | Time Frame |
|---|---|---|
| Transplant-related Mortality | Percentage of participants who die for any reason other than recurrence of disease. | Cumulative incidence for the entire study, up to 11 years |
| Relapse Rate | Percentage of participants who experience disease relapse. | Cumulative incidence for the entire study, up to 11 years |
| Progression-free Survival | Percentage of participants who do not experience disease relapse, disease progression, or death. | 2 years |
| Measure | Description | Time Frame |
|---|---|---|
| Graft Failure Rate | Percentage of participants who experienced failure to engraft (also called graft failure or graft rejection). Failure to engraft is defined as <5% donor chimerism and absence of relapse or any other reason for that chimerism value. All participants who met this criterion were included in this outcome measure. | Cumulative incidence for the entire study, up to 11 years |
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DISEASE CHARACTERISTICS:
Diagnosis of 1 of the following hematologic malignancies:
Acute leukemia
In second or subsequent complete remission (CR), as defined by absence of abnormal blast population by flow cytometry
In first CR with any of the following poor-risk cytogenetic features:
Chronic phase chronic myelogenous leukemia (CML)
Chronic lymphocytic leukemia, meeting 1 of the following criteria:
Received prior chemotherapy with a nucleoside analog and had remission lasting < 6 months
Received 1 prior therapy and has any of the following high-risk features:
Hodgkin's lymphoma
Ineligible for autologous stem cell transplantation (SCT) due to any of the following exclusion factors:
Non-Hodgkin's lymphoma (NHL)
Multiple myeloma
Myelodysplastic syndromes
Paroxysmal nocturnal hemoglobinuria
Chronic myeloproliferative disorders other than CML, including any of the following:
Chronic myelomonocytic leukemia
Agnogenic myeloid metaplasia (or myeloid metaplasia with myelofibrosis), with hemoglobin < 10 g/dL OR WBC < 4,000/mm^3 or > 30,000/mm^3
Polycythemia vera or essential thrombocythemia in "spent" phase, with a history of 2 of the following:
Polycythemia vera or essential thrombocythemia with transformation to myelodysplastic syndromes or acute myeloid leukemia (requires treatment to achieve < 20% blasts in marrow)
No smoldering myeloma
Patients with acute myeloid leukemia or myelodysplastic syndromes must have had comprehensive cytogenetic evaluation of bone marrow specimen during active disease
Ineligible for or refused bone marrow transplantation from an HLA-matched sibling or unrelated donor
Ineligible for or refused autologous SCT
Must have an HLA mismatched (i.e., 3/6, 4/6, or 5/6) related (first-degree relative)* donor available
NOTE: A new classification scheme for adult non-Hodgkin's lymphoma has been adopted by PDQ. The terminology of "indolent" or "aggressive" lymphoma will replace the former terminology of "low", "intermediate", or "high" grade lymphoma. However, this protocol uses the former terminology.
PATIENT CHARACTERISTICS:
Age
Performance status
Life expectancy
Hematopoietic
Hepatic
Renal
Cardiovascular
Pulmonary
Other
PRIOR CONCURRENT THERAPY:
Biologic therapy
Chemotherapy
Endocrine therapy
Radiotherapy
Surgery
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| Name | Affiliation | Role |
|---|---|---|
| Ephraim J. Fuchs, MD | Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Blood and Marrow Transplant Program at Northside Hospital | Atlanta | Georgia | 30342 | United States | ||
| Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins |
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| ID | Title | Description |
|---|---|---|
| FG000 | Mini-haplo BMT | Non-myeloablative haploidentical bone marrow transplant with a fludarabine, cyclophosphamide (Cy), TBI (total body irradiation) preparative regimen and post-transplant Cy, mycophenolate mofetil (MMF), and tacrolimus as GVHD prophylaxis. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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|
| mycophenolate mofetil | Drug |
|
| tacrolimus | Drug |
|
| allogeneic bone marrow transplantation | Procedure |
|
| radiation therapy | Radiation |
|
| Hematologic and Non-hematologic Toxicities as Measured by NCI Common Toxicity Criteria for Adverse Events, v 3.0 Weekly Until 1 Year After Transplantation | Percentage of study participants who experienced a serious adverse event (SAE) within 1 year of bone marrow transplant. Complete data is provided in the Adverse Event tables. | 1 year |
| Baltimore |
| Maryland |
| 21231-2410 |
| United States |
| Hahnemann University Hospital | Philadelphia | Pennsylvania | 19102-1192 | United States |
| COMPLETED |
|
| NOT COMPLETED |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Mini-haplo BMT | Non-myeloablative haploidentical bone marrow transplant with a fludarabine, cyclophosphamide (Cy), TBI (total body irradiation) preparative regimen and post-transplant Cy, mycophenolate mofetil (MMF), and tacrolimus as GVHD prophylaxis. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Full Range | years |
| |||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||||
| Region of Enrollment | Number | 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 | Transplant-related Mortality | Percentage of participants who die for any reason other than recurrence of disease. | Posted | Number | percentage of participants | Cumulative incidence for the entire study, up to 11 years |
|
|
| |||||||||||||||||||||||||||
| Primary | Relapse Rate | Percentage of participants who experience disease relapse. | Posted | Number | percentage of participants | Cumulative incidence for the entire study, up to 11 years |
|
| ||||||||||||||||||||||||||||
| Primary | Progression-free Survival | Percentage of participants who do not experience disease relapse, disease progression, or death. | Posted | Number | percentage of participants | 2 years |
|
| ||||||||||||||||||||||||||||
| Secondary | Graft Failure Rate | Percentage of participants who experienced failure to engraft (also called graft failure or graft rejection). Failure to engraft is defined as <5% donor chimerism and absence of relapse or any other reason for that chimerism value. All participants who met this criterion were included in this outcome measure. | Posted | Number | percentage of participants | Cumulative incidence for the entire study, up to 11 years |
|
| ||||||||||||||||||||||||||||
| Secondary | Hematologic and Non-hematologic Toxicities as Measured by NCI Common Toxicity Criteria for Adverse Events, v 3.0 Weekly Until 1 Year After Transplantation | Percentage of study participants who experienced a serious adverse event (SAE) within 1 year of bone marrow transplant. Complete data is provided in the Adverse Event tables. | Posted | Number | percentage of participants | 1 year |
|
|
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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 | Mini-haplo BMT | Non-myeloablative haploidentical bone marrow transplant with a fludarabine, cyclophosphamide (Cy), TBI (total body irradiation) preparative regimen and post-transplant Cy, mycophenolate mofetil (MMF), and tacrolimus as GVHD prophylaxis. | 20 | 210 | 11 | 210 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Atrial fibrillation | Cardiac disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Acute kidney injury | Renal and urinary disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Altered mental status | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Acute respiratory distress syndrome | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Ascites | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Cholestasis | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Dyspnea | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Fungemia | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
| |
| GI bleed | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Idiopathic pneumonia syndrome | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Multi-organ failure | Investigations | CTCAE (4.0) | Systematic Assessment |
| |
| Neutropenic fever | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
| |
| Posterior reversible encephalopathy syndrome | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Pulmonary Vascular Obstructive Disease | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Renal failure | Renal and urinary disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Seizure | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Sepsis | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
| |
| Subdural hematoma | Vascular disorders | CTCAE (4.0) | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pneumonia | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
|
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Ephraim Fuchs | Johns Hopkins University | 410-419-6479 | fuchsep@jhmi.edu |
| ID | Term |
|---|---|
| D009196 | Myeloproliferative Disorders |
| D007938 | Leukemia |
| D008223 | Lymphoma |
| D009101 | Multiple Myeloma |
| D054219 | Neoplasms, Plasma Cell |
| D009190 | Myelodysplastic Syndromes |
| D015466 | Leukemia, Myeloid, Chronic-Phase |
| D015451 | Leukemia, Lymphocytic, Chronic, B-Cell |
| D000013 | Congenital Abnormalities |
| D055728 | Primary Myelofibrosis |
| D015477 | Leukemia, Myelomonocytic, Chronic |
| D002051 | Burkitt Lymphoma |
| D016403 | Lymphoma, Large B-Cell, Diffuse |
| D008228 | Lymphoma, Non-Hodgkin |
| D006689 | Hodgkin Disease |
| D016400 | Lymphoma, Large-Cell, Immunoblastic |
| D054198 | Precursor Cell Lymphoblastic Leukemia-Lymphoma |
| D012008 | Recurrence |
| D054739 | Dendritic Cell Sarcoma, Interdigitating |
| D018442 | Lymphoma, B-Cell, Marginal Zone |
| D008224 | Lymphoma, Follicular |
| D020522 | Lymphoma, Mantle-Cell |
| D011087 | Polycythemia Vera |
| D013920 | Thrombocythemia, Essential |
| ID | Term |
|---|---|
| D001855 | Bone Marrow Diseases |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| D020141 | Hemostatic Disorders |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D010265 | Paraproteinemias |
| D001796 | Blood Protein Disorders |
| D006474 | Hemorrhagic Disorders |
| D015464 | Leukemia, Myelogenous, Chronic, BCR-ABL Positive |
| D007951 | Leukemia, Myeloid |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D015448 | Leukemia, B-Cell |
| D007945 | Leukemia, Lymphoid |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D054437 | Myelodysplastic-Myeloproliferative Diseases |
| D020031 | Epstein-Barr Virus Infections |
| D006566 | Herpesviridae Infections |
| D004266 | DNA Virus Infections |
| D014777 | Virus Diseases |
| D007239 | Infections |
| D014412 | Tumor Virus Infections |
| D016393 | Lymphoma, B-Cell |
| D015620 | Histiocytic Disorders, Malignant |
| D015614 | Histiocytosis |
| D019046 | Bone Marrow Neoplasms |
| D019337 | Hematologic Neoplasms |
| D009371 | Neoplasms by Site |
| D001778 | Blood Coagulation Disorders |
| D013922 | Thrombocytosis |
| D001791 | Blood Platelet Disorders |
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| ID | Term |
|---|---|
| D003520 | Cyclophosphamide |
| C042382 | fludarabine phosphate |
| D009173 | Mycophenolic Acid |
| D016559 | Tacrolimus |
| D011878 | Radiotherapy |
| ID | Term |
|---|---|
| D010752 | Phosphoramide Mustards |
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D063088 | Phosphoramides |
| D009943 | Organophosphorus Compounds |
| D002208 | Caproates |
| D000144 | Acids, Acyclic |
| D002264 | Carboxylic Acids |
| D005227 | Fatty Acids |
| D008055 | Lipids |
| D018942 | Macrolides |
| D007783 | Lactones |
| D013812 | Therapeutics |
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