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| Name | Class |
|---|---|
| Merck Sharp & Dohme LLC | INDUSTRY |
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AML is the most common acute leukemia in adults. Most patients can undergo allogeneic stem cell transplantation as a possible cure; however, many patients are not candidates for allogeneic transplant due to age, overall health, psychosocial factors, and/or lack of available donors. Therefore, these patients are unable to receive the therapeutic benefits of the "graft-versus-leukemia" effect of donor immune cells. The aim of this study is to hopefully break immune tolerance to AML cells to provide better outcomes in patients with non-favorable risk AML.
Non-favorable risk AML patients will undergo a preparative regimen of lymphodepletion of Flu/Mel followed by autologous transplantation. Anti-PD-1 therapy of pembrolizumab will begin on Day +1 following stem cell transplantation and will be administered every 3 weeks for a total of 8 doses. According to the literature, the risk of 2-year relapse is estimated to be 60-80% in patients with non-favorable risk AML in CR-1. With this protocol, investigators hypothesize that following lymphodepleting chemotherapy and pembrolizumab, the 2-year relapse risk will decrease to less than or equal to 35%. The one-sided Wald test at 5% significance level will be used to test the hypothesis. The size of 20 patients yields the power of 90.5% assuming that the actual 2-year leukemia-free survival is 60%.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Lymphodepletion plus Pembrolizumab | Experimental | Fludarabine & Melphalan followed by autologous stem cell transplantation. Pembrolizumab will begin on Day +1. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Fludarabine | Drug |
| ||
| Melphalan |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Patients With 2-year Relapse Risk | Hypothesis is that following lymphodepleting chemotherapy and pembrolizumab, the 2-year relapse risk will decrease to ≤35% | 2 years |
| Measure | Description | Time Frame |
|---|---|---|
| Assess Safety of Pembrolizumab by Recording the Number of Participants With Treatment-related Adverse Events | Assess safety of pembrolizumab in patients with AML following lymphodepleting chemotherapy | 6 months |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Scott Solomon, MD | Blood and Marrow Transplant Group of Georgia | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Blood and Marrow Transplant Group of Georgia | Atlanta | Georgia | 30342 | United States | ||
| Northside Hospital |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 17213292 | Result | Cornelissen JJ, van Putten WL, Verdonck LF, Theobald M, Jacky E, Daenen SM, van Marwijk Kooy M, Wijermans P, Schouten H, Huijgens PC, van der Lelie H, Fey M, Ferrant A, Maertens J, Gratwohl A, Lowenberg B. Results of a HOVON/SAKK donor versus no-donor analysis of myeloablative HLA-identical sibling stem cell transplantation in first remission acute myeloid leukemia in young and middle-aged adults: benefits for whom? Blood. 2007 May 1;109(9):3658-66. doi: 10.1182/blood-2006-06-025627. Epub 2007 Jan 9. | |
| 19509382 |
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| ID | Title | Description |
|---|---|---|
| FG000 | Lymphodepletion Plus Pembrolizumab | Fludarabine & Melphalan followed by autologous stem cell transplantation. Pembrolizumab will begin on Day +1. Fludarabine Melphalan Pembrolizumab |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Lymphodepletion Plus Pembrolizumab | Fludarabine & Melphalan followed by autologous stem cell transplantation. Pembrolizumab will begin on Day +1. Fludarabine Melphalan Pembrolizumab |
| 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 |
| 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 | Number of Patients With 2-year Relapse Risk | Hypothesis is that following lymphodepleting chemotherapy and pembrolizumab, the 2-year relapse risk will decrease to ≤35% | Posted | Count of Participants | Participants | 2 years |
|
|
6 months
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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 | Lymphodepletion Plus Pembrolizumab | Fludarabine & Melphalan followed by autologous stem cell transplantation. Pembrolizumab will begin on Day +1. Fludarabine Melphalan Pembrolizumab |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Neutropenic fever | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cytopenias | Blood and lymphatic system disorders | CTCAE (4.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Scott Solomon | The Blood and Marrow Transplant Group of Georgia/Northside Hospital | 404-255-1930 | ssolomon@bmtga.com |
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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 | Jul 6, 2021 | Aug 25, 2023 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D015470 | Leukemia, Myeloid, Acute |
| ID | Term |
|---|---|
| D007951 | Leukemia, Myeloid |
| D007938 | Leukemia |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
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| ID | Term |
|---|---|
| C024352 | fludarabine |
| D008558 | Melphalan |
| C582435 | pembrolizumab |
| ID | Term |
|---|---|
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
| D006838 | Hydrocarbons |
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|
| Pembrolizumab | Drug |
|
| Atlanta |
| Georgia |
| 30342 |
| United States |
| Result |
| Koreth J, Schlenk R, Kopecky KJ, Honda S, Sierra J, Djulbegovic BJ, Wadleigh M, DeAngelo DJ, Stone RM, Sakamaki H, Appelbaum FR, Dohner H, Antin JH, Soiffer RJ, Cutler C. Allogeneic stem cell transplantation for acute myeloid leukemia in first complete remission: systematic review and meta-analysis of prospective clinical trials. JAMA. 2009 Jun 10;301(22):2349-61. doi: 10.1001/jama.2009.813. |
| 12721664 | Result | Dong H, Chen L. B7-H1 pathway and its role in the evasion of tumor immunity. J Mol Med (Berl). 2003 May;81(5):281-7. doi: 10.1007/s00109-003-0430-2. Epub 2003 Apr 30. |
| 18756622 | Result | Chen X, Liu S, Wang L, Zhang W, Ji Y, Ma X. Clinical significance of B7-H1 (PD-L1) expression in human acute leukemia. Cancer Biol Ther. 2008 May;7(5):622-7. doi: 10.4161/cbt.7.5.5689. |
| 19423728 | Result | Ahmadzadeh M, Johnson LA, Heemskerk B, Wunderlich JR, Dudley ME, White DE, Rosenberg SA. Tumor antigen-specific CD8 T cells infiltrating the tumor express high levels of PD-1 and are functionally impaired. Blood. 2009 Aug 20;114(8):1537-44. doi: 10.1182/blood-2008-12-195792. Epub 2009 May 7. |
| 19188168 | Result | Gao Q, Wang XY, Qiu SJ, Yamato I, Sho M, Nakajima Y, Zhou J, Li BZ, Shi YH, Xiao YS, Xu Y, Fan J. Overexpression of PD-L1 significantly associates with tumor aggressiveness and postoperative recurrence in human hepatocellular carcinoma. Clin Cancer Res. 2009 Feb 1;15(3):971-9. doi: 10.1158/1078-0432.CCR-08-1608. |
| 15297412 | Result | Konishi J, Yamazaki K, Azuma M, Kinoshita I, Dosaka-Akita H, Nishimura M. B7-H1 expression on non-small cell lung cancer cells and its relationship with tumor-infiltrating lymphocytes and their PD-1 expression. Clin Cancer Res. 2004 Aug 1;10(15):5094-100. doi: 10.1158/1078-0432.CCR-04-0428. |
| 17363736 | Result | Liu J, Hamrouni A, Wolowiec D, Coiteux V, Kuliczkowski K, Hetuin D, Saudemont A, Quesnel B. Plasma cells from multiple myeloma patients express B7-H1 (PD-L1) and increase expression after stimulation with IFN-gamma and TLR ligands via a MyD88-, TRAF6-, and MEK-dependent pathway. Blood. 2007 Jul 1;110(1):296-304. doi: 10.1182/blood-2006-10-051482. Epub 2007 Mar 15. |
| 19420358 | Result | Mumprecht S, Schurch C, Schwaller J, Solenthaler M, Ochsenbein AF. Programmed death 1 signaling on chronic myeloid leukemia-specific T cells results in T-cell exhaustion and disease progression. Blood. 2009 Aug 20;114(8):1528-36. doi: 10.1182/blood-2008-09-179697. Epub 2009 May 6. |
| 18294387 | Result | Ghebeh H, Barhoush E, Tulbah A, Elkum N, Al-Tweigeri T, Dermime S. FOXP3+ Tregs and B7-H1+/PD-1+ T lymphocytes co-infiltrate the tumor tissues of high-risk breast cancer patients: Implication for immunotherapy. BMC Cancer. 2008 Feb 23;8:57. doi: 10.1186/1471-2407-8-57. |
| 17360651 | Result | Hamanishi J, Mandai M, Iwasaki M, Okazaki T, Tanaka Y, Yamaguchi K, Higuchi T, Yagi H, Takakura K, Minato N, Honjo T, Fujii S. Programmed cell death 1 ligand 1 and tumor-infiltrating CD8+ T lymphocytes are prognostic factors of human ovarian cancer. Proc Natl Acad Sci U S A. 2007 Feb 27;104(9):3360-5. doi: 10.1073/pnas.0611533104. Epub 2007 Feb 21. |
| 11015443 | Result | Freeman GJ, Long AJ, Iwai Y, Bourque K, Chernova T, Nishimura H, Fitz LJ, Malenkovich N, Okazaki T, Byrne MC, Horton HF, Fouser L, Carter L, Ling V, Bowman MR, Carreno BM, Collins M, Wood CR, Honjo T. Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J Exp Med. 2000 Oct 2;192(7):1027-34. doi: 10.1084/jem.192.7.1027. |
| 21105040 | Result | Shenghui Z, Yixiang H, Jianbo W, Kang Y, Laixi B, Yan Z, Xi X. Elevated frequencies of CD4(+) CD25(+) CD127lo regulatory T cells is associated to poor prognosis in patients with acute myeloid leukemia. Int J Cancer. 2011 Sep 15;129(6):1373-81. doi: 10.1002/ijc.25791. Epub 2011 Feb 26. |
| 19417016 | Result | Szczepanski MJ, Szajnik M, Czystowska M, Mandapathil M, Strauss L, Welsh A, Foon KA, Whiteside TL, Boyiadzis M. Increased frequency and suppression by regulatory T cells in patients with acute myelogenous leukemia. Clin Cancer Res. 2009 May 15;15(10):3325-32. doi: 10.1158/1078-0432.CCR-08-3010. Epub 2009 May 5. |
| 16313258 | Result | Wang X, Zheng J, Liu J, Yao J, He Y, Li X, Yu J, Yang J, Liu Z, Huang S. Increased population of CD4(+)CD25(high), regulatory T cells with their higher apoptotic and proliferating status in peripheral blood of acute myeloid leukemia patients. Eur J Haematol. 2005 Dec;75(6):468-76. doi: 10.1111/j.1600-0609.2005.00537.x. |
| 19724059 | Result | Zhou Q, Bucher C, Munger ME, Highfill SL, Tolar J, Munn DH, Levine BL, Riddle M, June CH, Vallera DA, Weigel BJ, Blazar BR. Depletion of endogenous tumor-associated regulatory T cells improves the efficacy of adoptive cytotoxic T-cell immunotherapy in murine acute myeloid leukemia. Blood. 2009 Oct 29;114(18):3793-802. doi: 10.1182/blood-2009-03-208181. Epub 2009 Sep 1. |
| 20570856 | Result | Zhou Q, Munger ME, Highfill SL, Tolar J, Weigel BJ, Riddle M, Sharpe AH, Vallera DA, Azuma M, Levine BL, June CH, Murphy WJ, Munn DH, Blazar BR. Program death-1 signaling and regulatory T cells collaborate to resist the function of adoptively transferred cytotoxic T lymphocytes in advanced acute myeloid leukemia. Blood. 2010 Oct 7;116(14):2484-93. doi: 10.1182/blood-2010-03-275446. Epub 2010 Jun 22. |
| 19023118 | Result | Shvets A, Chakrabarti R, Gonzalez-Quintial R, Baccala R, Theofilopoulos AN, Prud'homme GJ. Impaired negative regulation of homeostatically proliferating T cells. Blood. 2009 Jan 15;113(3):622-5. doi: 10.1182/blood-2008-03-139964. Epub 2008 Nov 20. |
| 17255288 | Result | Bracci L, Moschella F, Sestili P, La Sorsa V, Valentini M, Canini I, Baccarini S, Maccari S, Ramoni C, Belardelli F, Proietti E. Cyclophosphamide enhances the antitumor efficacy of adoptively transferred immune cells through the induction of cytokine expression, B-cell and T-cell homeostatic proliferation, and specific tumor infiltration. Clin Cancer Res. 2007 Jan 15;13(2 Pt 1):644-53. doi: 10.1158/1078-0432.CCR-06-1209. |
| 17273561 | Result | Wrzesinski C, Paulos CM, Gattinoni L, Palmer DC, Kaiser A, Yu Z, Rosenberg SA, Restifo NP. Hematopoietic stem cells promote the expansion and function of adoptively transferred antitumor CD8 T cells. J Clin Invest. 2007 Feb;117(2):492-501. doi: 10.1172/JCI30414. |
| 19952961 | Result | Wrzesinski C, Paulos CM, Kaiser A, Muranski P, Palmer DC, Gattinoni L, Yu Z, Rosenberg SA, Restifo NP. Increased intensity lymphodepletion enhances tumor treatment efficacy of adoptively transferred tumor-specific T cells. J Immunother. 2010 Jan;33(1):1-7. doi: 10.1097/CJI.0b013e3181b88ffc. |
| 12242449 | Result | Dudley ME, Wunderlich JR, Robbins PF, Yang JC, Hwu P, Schwartzentruber DJ, Topalian SL, Sherry R, Restifo NP, Hubicki AM, Robinson MR, Raffeld M, Duray P, Seipp CA, Rogers-Freezer L, Morton KE, Mavroukakis SA, White DE, Rosenberg SA. Cancer regression and autoimmunity in patients after clonal repopulation with antitumor lymphocytes. Science. 2002 Oct 25;298(5594):850-4. doi: 10.1126/science.1076514. Epub 2002 Sep 19. |
| 15800326 | Result | Dudley ME, Wunderlich JR, Yang JC, Sherry RM, Topalian SL, Restifo NP, Royal RE, Kammula U, White DE, Mavroukakis SA, Rogers LJ, Gracia GJ, Jones SA, Mangiameli DP, Pelletier MM, Gea-Banacloche J, Robinson MR, Berman DM, Filie AC, Abati A, Rosenberg SA. Adoptive cell transfer therapy following non-myeloablative but lymphodepleting chemotherapy for the treatment of patients with refractory metastatic melanoma. J Clin Oncol. 2005 Apr 1;23(10):2346-57. doi: 10.1200/JCO.2005.00.240. |
| 37379271 | Derived | Solomon SR, Solh M, Morris LE, Holland HK, Bachier-Rodriguez L, Zhang X, Guzowski C, Jackson KC, Brown S, Bashey A. Phase 2 study of PD-1 blockade following autologous transplantation for patients with AML ineligible for allogeneic transplant. Blood Adv. 2023 Sep 26;7(18):5215-5224. doi: 10.1182/bloodadvances.2023010477. |
| Participants |
|
| Age, Continuous | Median | Full Range | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
|
| Secondary | Assess Safety of Pembrolizumab by Recording the Number of Participants With Treatment-related Adverse Events | Assess safety of pembrolizumab in patients with AML following lymphodepleting chemotherapy | Posted | Count of Participants | Participants | 6 months |
|
|
|
| 1 |
| 20 |
| 12 |
| 20 |
| 20 |
| 20 |
| Diarrhea | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Weakness | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Failure to thrive | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Colitis | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Mucositis | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Right flank pain | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| Decreased appetite | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Non-neutropenic fever | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
|
| Hypotension | Cardiac disorders | CTCAE (4.0) | Systematic Assessment |
|
| Atrial fibrillation | Cardiac disorders | CTCAE (4.0) | Systematic Assessment |
|
| General infection | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
|
| Cytopenia | Blood and lymphatic system disorders | CTCAE (4.0) | Systematic Assessment |
|
| Radial fracture | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Colitis | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Mucositis | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Fatigue | General disorders | CTCAE (4.0) | Systematic Assessment |
|
| Hypertension | Cardiac disorders | CTCAE (4.0) | Systematic Assessment |
|
| Hypokalemia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
|
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| D006402 |
| Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D009930 |
| Organic Chemicals |
| D010649 | Phenylalanine |
| D024322 | Amino Acids, Aromatic |
| D000598 | Amino Acids, Cyclic |
| D000596 | Amino Acids |
| D000602 | Amino Acids, Peptides, and Proteins |