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| Name | Class |
|---|---|
| Blood and Marrow Transplant Group of Georgia | OTHER |
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This trial will evaluate the safety and efficacy of a reduced intensity allogeneic HSCT from partially HLA-mismatched first-degree relatives utilizing PBSC as the stem cell source. The primary objective of the study is to estimate the incidence of graft rejection and acute GVHD. A secondary objective will be to estimate the incidence of the relapse, NRM, OS, chronic GVHD and EFS.
Patients will receive a haploidentical transpalnt using a fludarabine melphalan prepartive regimen. Patients will get cyclophosphamide on days 3 & 4 post-transplant.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Reduced-Intensity Mismatched Transplant | Experimental | Fludarabine, Melphalan & Post-transplant cyclophosphamide |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Fludarabine | Drug | fludarabine (30mg/m2) given every day starting on Day -6 through Day -2; |
|
| Measure | Description | Time Frame |
|---|---|---|
| Graft Rejection | Measurement of donor cells vs. recipient cells | 100 days |
| Measure | Description | Time Frame |
|---|---|---|
| Overall Survival | Number of participants still alive 2 years after transplant | 2 years |
| Relapse Incidence | Number of patients with disease reoccurrence at 1 and 2 years post-transplant |
Not provided
Inclusion Criteria:
No available matched related or unrelated donor, OR a matched related or unrelated donor will not be available in time frame necessary to perform potentially curative transplant
Availability of 3/6 - 5/6 matched (HLA-A, B, DR) related donor (donor must have negative HLA cross-match in host vs. graft direction)
Karnofsky status ≥70%
One of the following high-risk malignancies:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Melhem Solh, MD | Northside Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Northside Hospital | Atlanta | Georgia | 30342 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 9164184 | Background | Szydlo R, Goldman JM, Klein JP, Gale RP, Ash RC, Bach FH, Bradley BA, Casper JT, Flomenberg N, Gajewski JL, Gluckman E, Henslee-Downey PJ, Hows JM, Jacobsen N, Kolb HJ, Lowenberg B, Masaoka T, Rowlings PA, Sondel PM, van Bekkum DW, van Rood JJ, Vowels MR, Zhang MJ, Horowitz MM. Results of allogeneic bone marrow transplants for leukemia using donors other than HLA-identical siblings. J Clin Oncol. 1997 May;15(5):1767-77. doi: 10.1200/JCO.1997.15.5.1767. | |
| 2643045 |
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| ID | Title | Description |
|---|---|---|
| FG000 | Reduced-Intensity Mismatched Transplant | Fludarabine, Melphalan & Post-transplant cyclophosphamide Fludarabine: fludarabine (30mg/m2) given every day starting on Day -6 through Day -2; Melphalan Cyclophosphamide: cyclophosphamide (50mg/kg) given every day starting on Day 3 through Day 4. peripheral blood stem cell transplant |
| 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 | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Oct 28, 2016 |
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| Melphalan | Drug |
|
|
| Cyclophosphamide | Drug | cyclophosphamide (50mg/kg) given every day starting on Day 3 through Day 4. |
|
|
| peripheral blood stem cell transplant | Procedure |
|
|
| 2 years |
| GVHD Incidence | The number of participants that developed graft-versus-host-disease before or at 100 days after transplant | 100 days |
| Background |
| Anasetti C, Amos D, Beatty PG, Appelbaum FR, Bensinger W, Buckner CD, Clift R, Doney K, Martin PJ, Mickelson E, et al. Effect of HLA compatibility on engraftment of bone marrow transplants in patients with leukemia or lymphoma. N Engl J Med. 1989 Jan 26;320(4):197-204. doi: 10.1056/NEJM198901263200401. |
| 3296349 | Background | Kernan NA, Flomenberg N, Dupont B, O'Reilly RJ. Graft rejection in recipients of T-cell-depleted HLA-nonidentical marrow transplants for leukemia. Identification of host-derived antidonor allocytotoxic T lymphocytes. Transplantation. 1987 Jun;43(6):842-7. |
| 15753458 | Background | Aversa F, Terenzi A, Tabilio A, Falzetti F, Carotti A, Ballanti S, Felicini R, Falcinelli F, Velardi A, Ruggeri L, Aloisi T, Saab JP, Santucci A, Perruccio K, Martelli MP, Mecucci C, Reisner Y, Martelli MF. Full haplotype-mismatched hematopoietic stem-cell transplantation: a phase II study in patients with acute leukemia at high risk of relapse. J Clin Oncol. 2005 May 20;23(15):3447-54. doi: 10.1200/JCO.2005.09.117. Epub 2005 Mar 7. |
| 24842530 | Background | Bashey A, Solomon SR. T-cell replete haploidentical donor transplantation using post-transplant CY: an emerging standard-of-care option for patients who lack an HLA-identical sibling donor. Bone Marrow Transplant. 2014 Aug;49(8):999-1008. doi: 10.1038/bmt.2014.62. Epub 2014 May 19. |
| 12171484 | Background | O'Donnell PV, Luznik L, Jones RJ, Vogelsang GB, Leffell MS, Phelps M, Rhubart P, Cowan K, Piantados S, Fuchs EJ. Nonmyeloablative bone marrow transplantation from partially HLA-mismatched related donors using posttransplantation cyclophosphamide. Biol Blood Marrow Transplant. 2002;8(7):377-86. doi: 10.1053/bbmt.2002.v8.pm12171484. |
| 22863841 | Background | Solomon SR, Sizemore CA, Sanacore M, Zhang X, Brown S, Holland HK, Morris LE, Bashey A. Haploidentical transplantation using T cell replete peripheral blood stem cells and myeloablative conditioning in patients with high-risk hematologic malignancies who lack conventional donors is well tolerated and produces excellent relapse-free survival: results of a prospective phase II trial. Biol Blood Marrow Transplant. 2012 Dec;18(12):1859-66. doi: 10.1016/j.bbmt.2012.06.019. Epub 2012 Aug 1. |
| 25797174 | Background | Solomon SR, Sizemore CA, Sanacore M, Zhang X, Brown S, Holland HK, Morris LE, Bashey A. Total Body Irradiation-Based Myeloablative Haploidentical Stem Cell Transplantation Is a Safe and Effective Alternative to Unrelated Donor Transplantation in Patients Without Matched Sibling Donors. Biol Blood Marrow Transplant. 2015 Jul;21(7):1299-307. doi: 10.1016/j.bbmt.2015.03.003. Epub 2015 Mar 19. |
| COMPLETED |
|
| NOT COMPLETED |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Reduced-Intensity Mismatched Transplant | Fludarabine, Melphalan & Post-transplant cyclophosphamide Fludarabine: fludarabine (30mg/m2) given every day starting on Day -6 through Day -2; Melphalan Cyclophosphamide: cyclophosphamide (50mg/kg) given every day starting on Day 3 through Day 4. peripheral blood stem cell transplant |
| 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 |
| ||||||||||||||||||
| Age, Continuous | Median | Full Range | years |
| |||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||||
| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | 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 | Graft Rejection | Measurement of donor cells vs. recipient cells | Posted | Count of Participants | Participants | 100 days |
|
|
| |||||||||||||||||||||||||||
| Secondary | Overall Survival | Number of participants still alive 2 years after transplant | Posted | Number | 95% Confidence Interval | percentage of patients | 2 years |
|
| |||||||||||||||||||||||||||
| Secondary | Relapse Incidence | Number of patients with disease reoccurrence at 1 and 2 years post-transplant | Posted | Number | 95% Confidence Interval | percentage of patients | 2 years |
|
| |||||||||||||||||||||||||||
| Secondary | GVHD Incidence | The number of participants that developed graft-versus-host-disease before or at 100 days after transplant | Posted | Number | 95% Confidence Interval | percentage of patients | 100 days |
|
|
100 days for adverse events, overall survival over 2 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 | Reduced-Intensity Mismatched Transplant | Fludarabine, Melphalan & Post-transplant cyclophosphamide Fludarabine: fludarabine (30mg/m2) given every day starting on Day -6 through Day -2; Melphalan Cyclophosphamide: cyclophosphamide (50mg/kg) given every day starting on Day 3 through Day 4. peripheral blood stem cell transplant | 3 | 25 | 23 | 25 | 25 | 25 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| respiratory failure | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
| ||
| confusion | Nervous system disorders | Non-systematic Assessment |
| ||
| sepsis | Infections and infestations | Non-systematic Assessment |
| ||
| renal failure | Renal and urinary disorders | Non-systematic Assessment |
| ||
| hypoxia | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
| ||
| pericardial effusion | Cardiac disorders | Non-systematic Assessment |
| ||
| pulmonary edema | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
| ||
| sinusitis | Infections and infestations | Non-systematic Assessment |
| ||
| esophagitis | Gastrointestinal disorders | Non-systematic Assessment |
| ||
| chest pain | General disorders | Non-systematic Assessment |
| ||
| mucositis | Gastrointestinal disorders | Non-systematic Assessment |
| ||
| tachycardia | Cardiac disorders | Non-systematic Assessment |
| ||
| elevated liver enzymes | Metabolism and nutrition disorders | Non-systematic Assessment |
| ||
| fever | General disorders | Non-systematic Assessment |
| ||
| hallucinations | Psychiatric disorders | Non-systematic Assessment |
| ||
| cardiac arrest | Cardiac disorders | Non-systematic Assessment |
| ||
| anorexia | Gastrointestinal disorders | Non-systematic Assessment |
| ||
| graft-versus-host-disease | Immune system disorders | Non-systematic Assessment |
| ||
| pneumonia | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
| ||
| bacteremia infection | Infections and infestations | Non-systematic Assessment |
| ||
| nausea | Gastrointestinal disorders | Non-systematic Assessment |
| ||
| vomiting | Gastrointestinal disorders | Non-systematic Assessment |
| ||
| diarrhea | Gastrointestinal disorders | Non-systematic Assessment |
| ||
| superficial venous thrombosis | Cardiac disorders | Non-systematic Assessment |
| ||
| hypotension | Cardiac disorders | Non-systematic Assessment |
| ||
| hypertension | Cardiac disorders | Non-systematic Assessment |
| ||
| thrombocytopenia | Investigations | Non-systematic Assessment |
| ||
| deep venous thrombosis | Cardiac disorders | Non-systematic Assessment |
| ||
| tumor lysis syndrome | Metabolism and nutrition disorders | Non-systematic Assessment |
| ||
| cytokine release syndrome | Immune system disorders | Non-systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| leukopenia | Investigations | Non-systematic Assessment |
| ||
| neutropenia | Investigations | Non-systematic Assessment |
| ||
| BK virus | Renal and urinary disorders | Non-systematic Assessment |
| ||
| anemia | Investigations | Non-systematic Assessment |
| ||
| rash | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
| ||
| hypokalemia | Metabolism and nutrition disorders | Non-systematic Assessment |
| ||
| hyponatremia | Metabolism and nutrition disorders | Non-systematic Assessment |
| ||
| weight loss | Gastrointestinal disorders | Non-systematic Assessment |
| ||
| syncope | Nervous system disorders | Non-systematic Assessment |
| ||
| hypocalcemia | Metabolism and nutrition disorders | Non-systematic Assessment |
| ||
| elevated liver enzymes | Metabolism and nutrition disorders | Non-systematic Assessment |
| ||
| hypertension | Cardiac disorders | Non-systematic Assessment |
| ||
| thrombocytopenia | Investigations | Non-systematic Assessment |
| ||
| urinary tract infection | Renal and urinary disorders | Non-systematic Assessment |
| ||
| hyperglycemia | Metabolism and nutrition disorders | Non-systematic Assessment |
| ||
| hypomagnesemia | Metabolism and nutrition disorders | Non-systematic Assessment |
| ||
| hypermagnesemia | Metabolism and nutrition disorders | Non-systematic Assessment |
|
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Melhem Solh | Northside Hospital | 404-255-1930 | msolh@bmtga.com |
| Apr 5, 2023 |
| Prot_SAP_000.pdf |
| ID | Term |
|---|---|
| D015464 | Leukemia, Myelogenous, Chronic, BCR-ABL Positive |
| D015470 | Leukemia, Myeloid, Acute |
| D009190 | Myelodysplastic Syndromes |
| D054198 | Precursor Cell Lymphoblastic Leukemia-Lymphoma |
| D015451 | Leukemia, Lymphocytic, Chronic, B-Cell |
| D006689 | Hodgkin Disease |
| D008228 | Lymphoma, Non-Hodgkin |
| D055728 | Primary Myelofibrosis |
| D009101 | Multiple Myeloma |
| ID | Term |
|---|---|
| D007951 | Leukemia, Myeloid |
| D007938 | Leukemia |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D009196 | Myeloproliferative Disorders |
| D001855 | Bone Marrow Diseases |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D007945 | Leukemia, Lymphoid |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| D015448 | Leukemia, B-Cell |
| D008223 | Lymphoma |
| D054219 | Neoplasms, Plasma Cell |
| D020141 | Hemostatic Disorders |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D010265 | Paraproteinemias |
| D001796 | Blood Protein Disorders |
| D006474 | Hemorrhagic Disorders |
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| ID | Term |
|---|---|
| C024352 | fludarabine |
| C042382 | fludarabine phosphate |
| D008558 | Melphalan |
| D003520 | Cyclophosphamide |
| D036102 | Peripheral Blood Stem Cell Transplantation |
| ID | Term |
|---|---|
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D010649 | Phenylalanine |
| D024322 | Amino Acids, Aromatic |
| D000598 | Amino Acids, Cyclic |
| D000596 | Amino Acids |
| D000602 | Amino Acids, Peptides, and Proteins |
| D010752 | Phosphoramide Mustards |
| D063088 | Phosphoramides |
| D009943 | Organophosphorus Compounds |
| 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 |
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| >=65 years |
|
| Title | Denominators | Categories | ||||
|---|---|---|---|---|---|---|
| 1 yr post-transplant |
| |||||
| 2 yr post-transplant |
|
| Title | Denominators | Categories | ||||
|---|---|---|---|---|---|---|
| 1 yr post-transplant |
| |||||
| 2 yr post-transplant |
|
| Title | Denominators | Categories | ||||
|---|---|---|---|---|---|---|
| Grades II to IV acute GVHD |
| |||||
| Grades III to IV acute GVHD |
| |||||
| Moderate chronic GVHD |
| |||||
| Severe chronic GVHD |
|