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| ID | Type | Description | Link |
|---|---|---|---|
| NCI-2010-00130 | Registry Identifier | CTRP (Clinical Trial Reporting Program) | |
| 1409.00 | 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 phase I/II trial studies how well autologous stem cell transplant followed by donor stem cell transplant works in treating patients with lymphoma that has returned or does not respond to treatment. Peripheral blood stem cell transplant using stem cells from the patient or a donor may be able to replace immune cells that were destroyed by chemotherapy used to kill cancer cells. The donated stem cells may also help destroy any remaining cancer cells (graft-versus-tumor effect).
PRIMARY OBJECTIVES:
I. To evaluate engraftment of human leukocyte antibody (HLA) identical peripheral blood stem cell (PBSC) allografts given after conditioning with total-body irradiation (TBI) (200cGy) +/- fludarabine (fludarabine phosphate), 90 mg/m^2 and post-grafting immunosuppression with cyclosporine (CSP)/mycophenolate mofetil (MMF) in refractory or relapsed lymphoma patients following an initial autologous peripheral blood stem cell transplant (PBSCT) for disease cytoreduction.
II. To determine the non-relapse mortality at day 100 post-non-myeloablative allografting following mobilization and high-dose chemotherapy with autografting.
SECONDARY OBJECTIVES:
I. To determine the disease free survival and overall survival of non-myeloablative allografting following autologous PBSCT.
OUTLINE:
CONDITIONING REGIMEN: Patients with matched, related stem cell donors receive cyclophosphamide intravenously (IV) on days -6 and -5 and undergo TBI twice daily (BID) on days -3 to -1. Patients with matched, unrelated stem cell donors receive carmustine IV over 3 hours on day -7, etoposide IV over 2 hours BID on days -6 to -3, and cytarabine IV over 3 hours BID on days -6 to -3, and melphalan IV over 30 minutes on day -2.
TRANSPLANTATION: All patients undergo autologous PBSCT on day 0.
NON-MYELOABLATIVE CONDITIONING: Beginning 40-120 days following PBSC transplant, patients with related donors undergo TBI on day 0. Patients with unrelated donors receive fludarabine phosphate IV over 30 minutes on days -4 to -2 and undergo TBI on day 0.
TRANSPLANTATION: Patients undergo non-myeloablative allogeneic PBSCT on day 0.
IMMUNOSUPPRESSION: Patients receive cyclosporine orally (PO) BID on days -3 to 56 (patients with related donors) or 100 (patients with unrelated donors) followed by taper to day 180. Patients also receive mycophenolate mofetil PO BID on days 0-27 (patients with related donors) or thrice daily (TID) on days 0-27, then BID on days 28-40 followed by taper to day 96 (patients with unrelated donors).
Some patients may undergo donor lymphocyte infusion if there is evidence of disease progression and no evidence of graft-vs-host disease (GVHD).
After completion of study treatment, patients are followed up at day 180, 1 year, 1.5 years, 2 years, 3 years, and then annually thereafter.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment (tandem transplantation) | Experimental | See Detailed Description |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Autologous Hematopoietic Stem Cell Transplantation | Procedure | Undergo autologous transplantation |
|
| Measure | Description | Time Frame |
|---|---|---|
| Engraftment of HLA Identical PBSC Allografts | Number of patients who engrafted by Day 56 post allogeneic transplant. Failure to engraft is defined as the absence of detectable donor cells in the marrow. The rates and accompanying confidence intervals associated with failure of engraftment at day +56 will be calculated after every 5th patient is enrolled on the study. If the lower limit to the appropriate one-sided 80% confidence interval exceeds 25%, this will be considered sufficient evidence of an excess "failure" rate and the study will be stopped. For these purposes, all patients will be evaluated together (patients with chemosensitive and chemoresistant disease). | Day 56 |
| Non-Relapse Mortality | The rates and accompanying confidence intervals associated with transplant-related mortality will be calculated after every 5th patient is enrolled on the study. If the lower limit to the appropriate one-sided 80% confidence interval exceeds 25%, this will be considered sufficient evidence of an excess "failure" rate and the study will be stopped. For these purposes, all patients will be evaluated together (patients with chemosensitive and chemoresistant disease). | Day 100 post-non-myeloablative allografting following mobilization and high-dose chemotherapy with autografting |
| Measure | Description | Time Frame |
|---|---|---|
| Overall Survival (OS) | Number of patients surviving by interval. Chemosensitive and chemoresistant subjects will be analyzed separately. | From the date of autologous transplant until the time of death, assessed up to 3 years |
| Progression Free-survival (PFS) |
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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 |
|---|---|---|---|---|---|---|
| Huntsman Cancer Institute/University of Utah | Salt Lake City | Utah | 84112 | United States | ||
| LDS Hospital |
| 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 (Tandem Transplantation) | See Detailed Description Autologous Hematopoietic Stem Cell Transplantation: Undergo autologous transplantation Autologous-Allogeneic Tandem Hematopoietic Stem Cell Transplantation: Undergo autologous-allogeneic tandem hematopoietic stem cell transplantation Carmustine: Given IV Cyclophosphamide: Given IV Cyclosporine: Given PO Cytarabine: Given IV Etoposide: Given IV Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Melphalan: Given IV Mycophenolate Mofetil: Given PO Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic transplantation Peripheral Blood Stem Cell Transplantation: Undergo allogeneic transplantation Therapeutic Autologous Lymphocytes: IV donor lymphocyte infusion Total-Body Irradiation: Undergo radiotherapy |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Autologous-Allogeneic Tandem Hematopoietic Stem Cell Transplantation | Procedure | Undergo autologous-allogeneic tandem hematopoietic stem cell transplantation |
|
|
| Carmustine | Drug | Given IV |
|
|
| Cyclophosphamide | Drug | Given IV |
|
|
| Cyclosporine | Drug | Given PO |
|
|
| Cytarabine | Drug | Given IV |
|
|
| Etoposide | Drug | Given IV |
|
|
| Fludarabine Phosphate | Drug | Given IV |
|
|
| Laboratory Biomarker Analysis | Other | Correlative studies |
|
| Melphalan | Drug | Given IV |
|
|
| Mycophenolate Mofetil | Drug | Given PO |
|
|
| Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation | Procedure | Undergo allogeneic transplantation |
|
|
| Peripheral Blood Stem Cell Transplantation | Procedure | Undergo allogeneic transplantation |
|
|
| Therapeutic Autologous Lymphocytes | Biological | IV donor lymphocyte infusion |
|
|
| Total-Body Irradiation | Radiation | Undergo radiotherapy |
|
|
Number of patients surviving without disease by interval. Chemosensitive and chemoresistant subjects will be analyzed separately. |
| From the date of autologous transplant until the time of progression, relapse, death, or the date the patient was last known to be in remission, assessed up to 3 years |
| Salt Lake City |
| Utah |
| 84143 |
| United States |
| VA Puget Sound Health Care System | Seattle | Washington | 98101 | United States |
| Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium | Seattle | Washington | 98109 | United States |
| Universitaet Leipzig | Leipzig | D-04103 | Germany |
| COMPLETED |
|
| NOT COMPLETED |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Treatment (Tandem Transplantation) | See Detailed Description Autologous Hematopoietic Stem Cell Transplantation: Undergo autologous transplantation Autologous-Allogeneic Tandem Hematopoietic Stem Cell Transplantation: Undergo autologous-allogeneic tandem hematopoietic stem cell transplantation Carmustine: Given IV Cyclophosphamide: Given IV Cyclosporine: Given PO Cytarabine: Given IV Etoposide: Given IV Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Melphalan: Given IV Mycophenolate Mofetil: Given PO Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic transplantation Peripheral Blood Stem Cell Transplantation: Undergo allogeneic transplantation Therapeutic Autologous Lymphocytes: IV donor lymphocyte infusion Total-Body Irradiation: Undergo radiotherapy |
| 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 |
| ||||||||||||||||||||
| Race (NIH/OMB) | 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 | Engraftment of HLA Identical PBSC Allografts | Number of patients who engrafted by Day 56 post allogeneic transplant. Failure to engraft is defined as the absence of detectable donor cells in the marrow. The rates and accompanying confidence intervals associated with failure of engraftment at day +56 will be calculated after every 5th patient is enrolled on the study. If the lower limit to the appropriate one-sided 80% confidence interval exceeds 25%, this will be considered sufficient evidence of an excess "failure" rate and the study will be stopped. For these purposes, all patients will be evaluated together (patients with chemosensitive and chemoresistant disease). | Only includes patients who received allo transplant. One patient is excluded because they did not survive long enough to test for engraftment. | Posted | Count of Participants | Participants | Day 56 |
|
|
| ||||||||||||||||||||||||||
| Primary | Non-Relapse Mortality | The rates and accompanying confidence intervals associated with transplant-related mortality will be calculated after every 5th patient is enrolled on the study. If the lower limit to the appropriate one-sided 80% confidence interval exceeds 25%, this will be considered sufficient evidence of an excess "failure" rate and the study will be stopped. For these purposes, all patients will be evaluated together (patients with chemosensitive and chemoresistant disease). | Although 54 patients received both auto transplant & allo transplant, one patient did not survive to day 100. | Posted | Count of Participants | Participants | Day 100 post-non-myeloablative allografting following mobilization and high-dose chemotherapy with autografting |
| ||||||||||||||||||||||||||||
| Secondary | Overall Survival (OS) | Number of patients surviving by interval. Chemosensitive and chemoresistant subjects will be analyzed separately. | One patient who counted to accrual is not included here. They received conditioning for autologous transplant, but then did not receive the transplant. | Posted | Count of Participants | Participants | From the date of autologous transplant until the time of death, assessed up to 3 years |
|
| |||||||||||||||||||||||||||
| Secondary | Progression Free-survival (PFS) | Number of patients surviving without disease by interval. Chemosensitive and chemoresistant subjects will be analyzed separately. | One patient who counted to accrual is not included here. They received conditioning for autologous transplant, but then did not receive the transplant. | Posted | Count of Participants | Participants | From the date of autologous transplant until the time of progression, relapse, death, or the date the patient was last known to be in remission, assessed up to 3 years |
|
|
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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 (Tandem Transplantation) | See Detailed Description Autologous Hematopoietic Stem Cell Transplantation: Undergo autologous transplantation Autologous-Allogeneic Tandem Hematopoietic Stem Cell Transplantation: Undergo autologous-allogeneic tandem hematopoietic stem cell transplantation Carmustine: Given IV Cyclophosphamide: Given IV Cyclosporine: Given PO Cytarabine: Given IV Etoposide: Given IV Fludarabine Phosphate: Given IV Laboratory Biomarker Analysis: Correlative studies Melphalan: Given IV Mycophenolate Mofetil: Given PO Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic transplantation Peripheral Blood Stem Cell Transplantation: Undergo allogeneic transplantation Therapeutic Autologous Lymphocytes: IV donor lymphocyte infusion Total-Body Irradiation: Undergo radiotherapy | 10 | 76 | 24 | 76 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Bowel perforation and sepsis | Infections and infestations | Non-systematic Assessment |
| ||
| Sepsis with respiratory failure and mental status changes | Infections and infestations | Non-systematic Assessment |
| ||
| Tachycardia, intubation, sepsis and pulmonary embolus | Infections and infestations | Non-systematic Assessment |
| ||
| Death due to multiple pulmonary infections | Infections and infestations | Non-systematic Assessment |
| ||
| Pulmonary failure requiring intubation | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
| ||
| Death due to infection with pericardial and epicardial involvement | Infections and infestations | Non-systematic Assessment |
| ||
| Respiratory arrest due to disease progression | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
| ||
| Hypoxia due to organizing pneumonitis | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
| ||
| Hypoxemia during PBSC infusion | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
| ||
| Pulmonary Embolism | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
| ||
| Intra-abdominal hemorrhage when undergoing VATS procedure | Surgical and medical procedures | Non-systematic Assessment |
| ||
| Seizures | General disorders | Non-systematic Assessment | no etilogy for the seizures identified |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hyperbilirubinemia | Hepatobiliary disorders | Systematic Assessment |
| ||
| Increased Creatinine | Renal and urinary disorders | Systematic Assessment |
| ||
| Hypoxia | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
| ||
| Diffuse Alveolar Hemorrhage | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
|
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| David G Maloney, MD PhD | Fred Hutch | dmaloney@fredhutch.org |
| ID | Term |
|---|---|
| D015463 | Leukemia, Prolymphocytic |
| D006689 | Hodgkin Disease |
| D015451 | Leukemia, Lymphocytic, Chronic, B-Cell |
| D008228 | Lymphoma, Non-Hodgkin |
| D015461 | Leukemia, Prolymphocytic, T-Cell |
| 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 |
| D008223 | Lymphoma |
| D015448 | Leukemia, B-Cell |
| 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 |
|---|---|
| D002330 | Carmustine |
| C574855 | carmustine, poliferprosan 20 drug combination |
| D003520 | Cyclophosphamide |
| D016572 | Cyclosporine |
| D003524 | Cyclosporins |
| D003561 | Cytarabine |
| D005047 | Etoposide |
| C042382 | fludarabine phosphate |
| D008558 | Melphalan |
| D009173 | Mycophenolic Acid |
| D036102 | Peripheral Blood Stem Cell Transplantation |
| D014916 | Whole-Body Irradiation |
| ID | Term |
|---|---|
| D009607 | Nitrosourea Compounds |
| D014508 | Urea |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D009603 | Nitroso Compounds |
| D010752 | Phosphoramide Mustards |
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
| D006838 | Hydrocarbons |
| D063088 | Phosphoramides |
| D009943 | Organophosphorus Compounds |
| D010456 | Peptides, Cyclic |
| D047028 | Macrocyclic Compounds |
| D011083 | Polycyclic Compounds |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D001087 | Arabinonucleosides |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| D011034 | Podophyllotoxin |
| D013764 | Tetrahydronaphthalenes |
| D009281 | Naphthalenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D005960 | Glucosides |
| D006027 | Glycosides |
| D002241 | Carbohydrates |
| D010649 | Phenylalanine |
| D024322 | Amino Acids, Aromatic |
| D000598 | Amino Acids, Cyclic |
| D000596 | Amino Acids |
| D002208 | Caproates |
| D000144 | Acids, Acyclic |
| D002264 | Carboxylic Acids |
| D005227 | Fatty Acids |
| D008055 | Lipids |
| D018380 | Hematopoietic Stem Cell Transplantation |
| D033581 | Stem Cell Transplantation |
| D017690 | Cell Transplantation |
| D064987 | Cell- and Tissue-Based Therapy |
| D001691 | Biological Therapy |
| D013812 | Therapeutics |
| D014180 | Transplantation |
| D013514 | Surgical Procedures, Operative |
| D011878 | Radiotherapy |
| D008919 | Investigative Techniques |
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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 |
|
| Units | Counts |
|---|---|
| Participants |
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