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| ID | Type | Description | Link |
|---|---|---|---|
| NCI-2010-01276 | Registry Identifier | CTRP (Clinical Trial Reporting Program) | |
| NCI-2011-01116 | |||
| 1711.00 | Other Identifier | Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium | |
| P30CA015704 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Cancer Institute (NCI) | NIH |
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This clinical trial studies how well giving fludarabine phosphate together with total-body irradiation (TBI) before donor peripheral blood stem cell transplant works in treating patients with chronic lymphocytic leukemia or small lymphocytic leukemia. Giving low doses of chemotherapy, such as fludarabine phosphate, and TBI before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. Giving chemotherapy before or after peripheral blood stem cell transplant also stops the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune 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 cyclosporine and mycophenolate mofetil before and after the transplant may stop this from happening.
PRIMARY OBJECTIVES:
I. To determine whether nonmyeloablative allogeneic hematopoietic stem cell transplantation (HSCT) from matched-related donors can improve the probability of survival 18 months after treatment for fludarabine (fludarabine phosphate)-refractory, fludarabine phosphate, cyclophosphamide, and rituximab (FCR)-failed, or del 17p chronic lymphocytic leukemia (CLL) beyond that observed in historical controls (30%).
SECONDARY OBJECTIVES:
I. To assess the rate of relapse with allogeneic HSCT using nonmyeloablative conditioning for patients with fludarabine-refractory, FCR-failed, or del 17p CLL compared with historical data on autologous HSCT.
II. To estimate the incidence of grade 2-4 acute graft-versus-host disease (GVHD) and chronic GVHD in patients with CLL treated with low-dose TBI, fludarabine, peripheral blood stem cell (PBSC) infusion and immunosuppression with cyclosporine and mycophenolate mofetil.
III. To characterize the rate and types of infections with this regimen.
IV. To estimate the rate of transplant-related mortality in the first 200 days.
OUTLINE:
NONMYELOABLATIVE CONDITIONING: Patients receive fludarabine phosphate intravenously (IV) on days -4 to -2 and TBI on day 0.
TRANSPLANT: Patients undergo allogeneic peripheral blood stem cell transplant on day 0.
GVHD PROPHYLAXIS: Patients receive cyclosporine orally (PO) every 12 hours on days -3 to 180 with taper beginning on day 56 and mycophenolate mofetil PO every 12 hours on days 0-27.
After completion of study treatment, patients are followed up at 12 and 18 months and then annually for 5 years.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment (enzyme inhibitor, transplant, GVHD prophylaxis) | Experimental | NONMYELOABLATIVE CONDITIONING: Patients receive fludarabine phosphate IV on days -4 to -2 and TBI on day 0. TRANSPLANT: Patients undergo allogeneic peripheral blood stem cell transplant on day 0. GVHD PROPHYLAXIS: Patients receive cyclosporine PO every 12 hours on days -3 to 180 with taper on day 56 and mycophenolate mofetil PO every 12 hours on days 0-27. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Cyclosporine | Drug | Given PO |
|
| Measure | Description | Time Frame |
|---|---|---|
| Overall Survival | Number of patients surviving 18 months post-transplant. | At 18 months |
| Measure | Description | Time Frame |
|---|---|---|
| Rate of Relapse | Number of patients with relapsed disease post-transplant. Relapse/progression is defined as 1) Physical exam/Imaging studies (nodes, liver, and/or spleen) ≥50% increase or new, 2) circulating lymphocytes by morphology and/or flow cytometry ≥50% increase, or 3) lymph node Biopsy Richter's transformation. | 18 months |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| David Maloney | Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Veterans Administration Center-Seattle | Seattle | Washington | 98108 | United States | ||
| Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32499241 | Derived | Cooper JP, Storer BE, Granot N, Gyurkocza B, Sorror ML, Chauncey TR, Shizuru J, Franke GN, Maris MB, Boyer M, Bruno B, Sahebi F, Langston AA, Hari P, Agura ED, Lykke Petersen S, Maziarz RT, Bethge W, Asch J, Gutman JA, Olesen G, Yeager AM, Hubel K, Hogan WJ, Maloney DG, Mielcarek M, Martin PJ, Flowers MED, Georges GE, Woolfrey AE, Deeg JH, Scott BL, McDonald GB, Storb R, Sandmaier BM. Allogeneic hematopoietic cell transplantation with non-myeloablative conditioning for patients with hematologic malignancies: Improved outcomes over two decades. Haematologica. 2021 Jun 1;106(6):1599-1607. doi: 10.3324/haematol.2020.248187. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Treatment (Enzyme Inhibitor, Transplant, GVHD Prophylaxis) | NONMYELOABLATIVE CONDITIONING: Patients receive fludarabine phosphate IV on days -4 to -2 and TBI on day 0. TRANSPLANT: Patients undergo allogeneic peripheral blood stem cell transplant on day 0. GVHD PROPHYLAXIS: Patients receive cyclosporine PO every 12 hours on days -3 to 180 with taper on day 56 and mycophenolate mofetil PO every 12 hours on days 0-27. Cyclosporine: Given PO Fludarabine Phosphate: Given IV Hematopoietic Cell Transplantation: Undergo allogeneic peripheral blood stem cell transplant Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given PO Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic peripheral blood stem cell transplant Total-Body Irradiation: Undergo TBI |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Fludarabine Phosphate | Drug | Given IV |
|
|
| Hematopoietic Cell Transplantation | Procedure | Undergo allogeneic peripheral blood stem cell transplant |
|
|
| Laboratory Biomarker Analysis | Other | Correlative studies |
|
| Mycophenolate Mofetil | Drug | Given PO |
|
|
| Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation | Procedure | Undergo allogeneic peripheral blood stem cell transplant |
|
|
| Total-Body Irradiation | Radiation | Undergo TBI |
|
|
| Acute Grade II-IV GVHD and Chronic (Extensive) GVHD |
Number of patients who developed acute/chronic GVHD post-transplant. aGVHD Stages Skin: a maculopapular eruption involving < 25% BSA a maculopapular eruption involving 25 - 50% BSA generalized erythroderma generalized erythroderma with bullous formation and often with desquamation Liver: bilirubin 2.0 - 3.0 mg/100 mL bilirubin 3 - 5.9 mg/100 mL bilirubin 6 - 14.9 mg/100 mL bilirubin > 15 mg/100 mL Gut: Diarrhea is graded 1 - 4 in severity. Nausea and vomiting and/or anorexia caused by GVHD is assigned as 1 in severity. The severity of gut involvement is assigned to the most severe involvement noted. Patients with visible bloody diarrhea are at least stage 2 gut and grade 3 overall. aGVHD Grades Grade II: Stage 1 - 3 skin and/or stage 1 gut involvement and/or stage 1 liver involvement Grade III: Stage 2 - 4 gut involvement and/or stage 2 - 4 liver involvement Grade IV: Pattern and severity of GVHD similar to grade 3 with extreme constitutional symptoms or death |
| aGVHD: 100 days after transplant; cGVHD: 1 Year after transplant. |
| Rate and Types of Infections | Number of infections patients experienced, by infection type. | 18 months |
| Transplant-related Mortality | Defined as death before day +200 not related to progression of disease. | At 200 days |
| Seattle |
| Washington |
| 98109 |
| United States |
| University of Torino | Torino | 10126 | Italy |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Treatment (Enzyme Inhibitor, Transplant, GVHD Prophylaxis) | NONMYELOABLATIVE CONDITIONING: Patients receive fludarabine phosphate IV on days -4 to -2 and TBI on day 0. TRANSPLANT: Patients undergo allogeneic peripheral blood stem cell transplant on day 0. GVHD PROPHYLAXIS: Patients receive cyclosporine PO every 12 hours on days -3 to 180 with taper on day 56 and mycophenolate mofetil PO every 12 hours on days 0-27. Cyclosporine: Given PO Fludarabine Phosphate: Given IV Hematopoietic Cell Transplantation: Undergo allogeneic peripheral blood stem cell transplant Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given PO Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic peripheral blood stem cell transplant Total-Body Irradiation: Undergo TBI |
| 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 | Participants |
| |||||||||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| |||||||||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
| |||||||||||||||||||||||
| Region of Enrollment | Number | participants |
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| 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 | Number of patients surviving 18 months post-transplant. | Posted | Count of Participants | Participants | At 18 months |
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| |||||||||||||||||||||||||||
| Secondary | Rate of Relapse | Number of patients with relapsed disease post-transplant. Relapse/progression is defined as 1) Physical exam/Imaging studies (nodes, liver, and/or spleen) ≥50% increase or new, 2) circulating lymphocytes by morphology and/or flow cytometry ≥50% increase, or 3) lymph node Biopsy Richter's transformation. | Posted | Count of Participants | Participants | 18 months |
|
| ||||||||||||||||||||||||||||
| Secondary | Acute Grade II-IV GVHD and Chronic (Extensive) GVHD | Number of patients who developed acute/chronic GVHD post-transplant. aGVHD Stages Skin: a maculopapular eruption involving < 25% BSA a maculopapular eruption involving 25 - 50% BSA generalized erythroderma generalized erythroderma with bullous formation and often with desquamation Liver: bilirubin 2.0 - 3.0 mg/100 mL bilirubin 3 - 5.9 mg/100 mL bilirubin 6 - 14.9 mg/100 mL bilirubin > 15 mg/100 mL Gut: Diarrhea is graded 1 - 4 in severity. Nausea and vomiting and/or anorexia caused by GVHD is assigned as 1 in severity. The severity of gut involvement is assigned to the most severe involvement noted. Patients with visible bloody diarrhea are at least stage 2 gut and grade 3 overall. aGVHD Grades Grade II: Stage 1 - 3 skin and/or stage 1 gut involvement and/or stage 1 liver involvement Grade III: Stage 2 - 4 gut involvement and/or stage 2 - 4 liver involvement Grade IV: Pattern and severity of GVHD similar to grade 3 with extreme constitutional symptoms or death | Posted | Count of Participants | Participants | aGVHD: 100 days after transplant; cGVHD: 1 Year after transplant. |
| |||||||||||||||||||||||||||||
| Secondary | Rate and Types of Infections | Number of infections patients experienced, by infection type. | Posted | Number | infections | 18 months |
|
| ||||||||||||||||||||||||||||
| Secondary | Transplant-related Mortality | Defined as death before day +200 not related to progression of disease. | Posted | Count of Participants | Participants | At 200 days |
|
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AEs: Conditioning through Day 100; SAEs: Conditioning through Day 200
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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 | Treatment (Enzyme Inhibitor, Transplant, GVHD Prophylaxis) | NONMYELOABLATIVE CONDITIONING: Patients receive fludarabine phosphate IV on days -4 to -2 and TBI on day 0. TRANSPLANT: Patients undergo allogeneic peripheral blood stem cell transplant on day 0. GVHD PROPHYLAXIS: Patients receive cyclosporine PO every 12 hours on days -3 to 180 with taper on day 56 and mycophenolate mofetil PO every 12 hours on days 0-27. Cyclosporine: Given PO Fludarabine Phosphate: Given IV Hematopoietic Cell Transplantation: Undergo allogeneic peripheral blood stem cell transplant Laboratory Biomarker Analysis: Correlative studies Mycophenolate Mofetil: Given PO Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic peripheral blood stem cell transplant Total-Body Irradiation: Undergo TBI | 7 | 21 | 15 | 21 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Death following progression of GVHD | Immune system disorders | Non-systematic Assessment |
| ||
| Death following disease progression post transplant | Immune system disorders | Non-systematic Assessment |
| ||
| Cardiac Arrhythmia and Seizure | Cardiac disorders | Non-systematic Assessment |
| ||
| Death: Sepsis/Renal failure/ with history of GVHD | Renal and urinary disorders | Non-systematic Assessment |
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| Severe abnormal pain due to gut GVH | Gastrointestinal disorders | Non-systematic Assessment |
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| Acute Pulmonary Embolism | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
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| Perforated sigmoid diverticulitis | Gastrointestinal disorders | Non-systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Neutropenia | Blood and lymphatic system disorders | Systematic Assessment | Grades 3, 4 |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | Systematic Assessment | Grades 3, 4 |
| |
| Minimal hydronephosis | Renal and urinary disorders | Non-systematic Assessment |
| ||
| Cholecystectomy | Surgical and medical procedures | Non-systematic Assessment |
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| Acute Pulmonary Embolism | Cardiac disorders | Non-systematic Assessment |
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| Hyperbilirubinemia | Hepatobiliary disorders | Systematic Assessment |
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| Hypotension | Cardiac disorders | Non-systematic Assessment |
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| Hypoxia | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
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| Increased creatinine | Renal and urinary disorders | Systematic Assessment |
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| Neurotoxicity | Nervous system disorders | Non-systematic Assessment | due to ifosfamide |
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| Renal failure | Renal and urinary disorders | Non-systematic Assessment |
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| Tumor lysis syndrome | Blood and lymphatic system disorders | Systematic Assessment | Uric acid level of 10.4 mg/dL. |
| |
| Typhlitis & Bowel Perforation | Gastrointestinal disorders | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| David G Maloney, MD PhD | Fred Hutch | dmaloney@fredhutch.org |
| ID | Term |
|---|---|
| D054403 | Leukemia, Prolymphocytic, B-Cell |
| D015451 | Leukemia, Lymphocytic, Chronic, B-Cell |
| D015463 | Leukemia, Prolymphocytic |
| D015461 | Leukemia, Prolymphocytic, T-Cell |
| ID | Term |
|---|---|
| D015448 | Leukemia, B-Cell |
| 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 |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D015458 | Leukemia, T-Cell |
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| ID | Term |
|---|---|
| D016572 | Cyclosporine |
| D003524 | Cyclosporins |
| C042382 | fludarabine phosphate |
| D033581 | Stem Cell Transplantation |
| D018380 | Hematopoietic Stem Cell Transplantation |
| D009173 | Mycophenolic Acid |
| D014916 | Whole-Body Irradiation |
| ID | Term |
|---|---|
| D010456 | Peptides, Cyclic |
| D047028 | Macrocyclic Compounds |
| D011083 | Polycyclic Compounds |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D017690 | Cell Transplantation |
| D064987 | Cell- and Tissue-Based Therapy |
| D001691 | Biological Therapy |
| D013812 | Therapeutics |
| D014180 | Transplantation |
| D013514 | Surgical Procedures, Operative |
| D002208 | Caproates |
| D000144 | Acids, Acyclic |
| D002264 | Carboxylic Acids |
| D009930 | Organic Chemicals |
| D005227 | Fatty Acids |
| D008055 | Lipids |
| D011878 | Radiotherapy |
| D008919 | Investigative Techniques |
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| Unknown or Not Reported |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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