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| Name | Class |
|---|---|
| Bristol-Myers Squibb | INDUSTRY |
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The purpose of this study is to investigate whether the combination of cyclophosphamide and abatacept versus the treatment used in standard of care will reduce the incidence of moderate and severe chronic graft-versus-host disease (GVHD) following hematopoietic stem cell transplantation. GVHD occurs when the cells from your donor (the graft) see your body's cells (the host) as different and attack them.
The experimental GVHD prophylaxis arm consists of cyclophosphamide and abatacept. Cyclophosphamide induces apoptosis of activated T cells and abatacept (CTLA4Ig) blocks activation of T cells by inhibiting the co-stimulatory signal.
Compared to the standard-of-care control arm, the experimental arm is much more convenient and expected to be associated with fewer toxicities.
In addition there is a great theoretical potential for immunological synergy between cyclophosphamide and abatacept for inducing post-transplant immunologic tolerance that clinically might translate into less GVHD without increase in relapse Patients will be randomized 1:1 to the experimental vs the standard of care arm. Randomization will be done prior to the use of any conditional therapy.
The two arms will be stratified by disease (acute leukemia vs others) and donor type (MRD vs MUD/MUD vs Haplo) in an effort to keep them balanced.
The conditioning regimen for both arms will be mainly Busulfan/Fludarabine (A Total Body Irradiation based conditioning regimen will be allowed for diseases such as ALL)
The GVHD prophylaxis regimen on the experimental arm will consist of high dose Cyclophosphamide on Days +3 and +4 followed by abatacept for 6 months.
The GVHD prophylaxis regimen on the standard of care arm will consist of methotrexate on Days +1,+3, +6 and +11 and tacrolimus for patients with a 10/10 matched related or unrelated donor and of high dose cyclophosphamide on Days +3 and +4 followed by tacrolimus and mycophenolate for patients with a haploidentical donor.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cyclophosphamide and abatacept | Experimental | The GVHD prophylaxis regimen on the experimental arm will consist of high dose Cyclophosphamide on Days +3 and +4 followed by abatacept for 6 months. Abatacept at a dose of 10mg/kg will be administered on days +5, +14 and +28, +56, +84, +112, +140, +168 |
|
| methotrexate and tacrolimus | Active Comparator | The GVHD prophylaxis regimen on the standard of care arm will consist of methotrexate on Days +1,+3, +6 and +11 and tacrolimus |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Cyclophosphamide | Drug | Day 3 and day 4 following transplant. Dosing will be based on patients' actual weight up to 120% of ideal body weight, above which it will be based on adjusted ideal body weight (ideal weight plus 50% of the difference between ideal and actual weight). |
| Measure | Description | Time Frame |
|---|---|---|
| Occurrence of Moderate and Severe Chronic GVHD at One Year Post Transplant | The occurrence of moderate and severe chronic GVHD at one year post Chronic GVHD will be diagnosed and staged according to the previously published and widely accepted National Institutes of Health consensus criteria | through study completion, an average of 1 year |
| Measure | Description | Time Frame |
|---|---|---|
| GVHD- and Relapse- Free Survival by One Year Post Transplant | GVHD- and relapse- free survival will be defined as the absence of acute GVHD Grade III or IV or moderate or severe chronic GVHD or relapse or non-relapse mortality by one year post transplant. Acute GVHD will be diagnosed and graded according to Glucksberg criteria | through study completion, an average of 1 year |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Dimitrios Tzachanis, MD PhD | University of California, San Diego | Principal Investigator |
| Divya Koura, MD | University of California, San Diego | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UC San Diego Moores Cancer Center | La Jolla | California | 92093 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 40554429 | Derived | Koura D, Dykes K, Goodman A, Costello C, Mulroney C, Mangan JK, Tanaka TN, Ball ED, Hamdan A, Jeong AR, Mirocha J, Zhang Q, Ogrodnik P, McConnell K, Maroge JJ, Padilla M, Morris GP, Tzachanis D. A prospective clinical trial of GVHD prophylaxis with posttransplant cyclophosphamide and abatacept. Blood Adv. 2025 Aug 26;9(16):4336-4344. doi: 10.1182/bloodadvances.2024015094. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Cyclophosphamide and Abatacept | The GVHD prophylaxis regimen on the experimental arm will consist of high dose Cyclophosphamide on Days +3 and +4 followed by abatacept for 6 months. Abatacept at a dose of 10mg/kg will be administered on days +5, +14 and +28, +56, +84, +112, +140, +168 Cyclophosphamide: Day 3 and day 4 following transplant. Dosing will be based on patients' actual weight up to 120% of ideal body weight, above which it will be based on adjusted ideal body weight (ideal weight plus 50% of the difference between ideal and actual weight). abatacept: Abatacept at a dose of 10mg/kg will be administered on days +5, +14 and +28, +56, +84, +112, +140, +168 |
| FG001 | Methotrexate and Tacrolimus | The GVHD prophylaxis regimen on the standard of care arm will consist of methotrexate on Days +1,+3, +6 and +11 and tacrolimus Methotrexate: standard of care Methotrexate 5 mg/m2 on Days 1, 3, 6 and 11 Tacrolimus: Tacrolimus per institutional guidelines |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Cyclophosphamide and Abatacept | The GVHD prophylaxis regimen on the experimental arm will consist of high dose Cyclophosphamide on Days +3 and +4 followed by abatacept for 6 months. Abatacept at a dose of 10mg/kg will be administered on days +5, +14 and +28, +56, +84, +112, +140, +168 Cyclophosphamide: Day 3 and day 4 following transplant. Dosing will be based on patients' actual weight up to 120% of ideal body weight, above which it will be based on adjusted ideal body weight (ideal weight plus 50% of the difference between ideal and actual weight). abatacept: Abatacept at a dose of 10mg/kg will be administered on days +5, +14 and +28, +56, +84, +112, +140, +168 |
| 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 | Occurrence of Moderate and Severe Chronic GVHD at One Year Post Transplant | The occurrence of moderate and severe chronic GVHD at one year post Chronic GVHD will be diagnosed and staged according to the previously published and widely accepted National Institutes of Health consensus criteria | Posted | Count of Participants | Participants | through study completion, an average of 1 year |
|
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 | Cyclophosphamide and Abatacept | The GVHD prophylaxis regimen on the experimental arm will consist of high dose Cyclophosphamide on Days +3 and +4 followed by abatacept for 6 months. Abatacept at a dose of 10mg/kg will be administered on days +5, +14 and +28, +56, +84, +112, +140, +168 Cyclophosphamide: Day 3 and day 4 following transplant. Dosing will be based on patients' actual weight up to 120% of ideal body weight, above which it will be based on adjusted ideal body weight (ideal weight plus 50% of the difference between ideal and actual weight). abatacept: Abatacept at a dose of 10mg/kg will be administered on days +5, +14 and +28, +56, +84, +112, +140, +168 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Febrile Neutropenia | Infections and infestations | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| CMV Viremia | Infections and infestations | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Dimitrios Tzachanis | University of California, San Diego | (858) 822-6600 | dtzachanis@health.ucsd.edu |
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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 | Jan 10, 2022 | Sep 4, 2024 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D019337 | Hematologic Neoplasms |
| D009369 | Neoplasms |
| D006086 | Graft vs Host Disease |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D007154 | Immune System Diseases |
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| ID | Term |
|---|---|
| D003520 | Cyclophosphamide |
| D000069594 | Abatacept |
| D008727 | Methotrexate |
| D016559 | Tacrolimus |
| ID | Term |
|---|---|
| D010752 | Phosphoramide Mustards |
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
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|
| abatacept | Drug | Abatacept at a dose of 10mg/kg will be administered on days +5, +14 and +28, +56, +84, +112, +140, +168 |
|
|
| Methotrexate | Drug | standard of care Methotrexate 5 mg/m2 on Days 1, 3, 6 and 11 |
|
|
| Tacrolimus | Drug | Tacrolimus per institutional guidelines |
|
|
| BG001 | Methotrexate and Tacrolimus | The GVHD prophylaxis regimen on the standard of care arm will consist of methotrexate on Days +1,+3, +6 and +11 and tacrolimus Methotrexate: standard of care Methotrexate 5 mg/m2 on Days 1, 3, 6 and 11 Tacrolimus: Tacrolimus per institutional guidelines |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| OG001 | Methotrexate and Tacrolimus | The GVHD prophylaxis regimen on the standard of care arm will consist of methotrexate on Days +1,+3, +6 and +11 and tacrolimus Methotrexate: standard of care Methotrexate 5 mg/m2 on Days 1, 3, 6 and 11 Tacrolimus: Tacrolimus per institutional guidelines |
|
|
| Secondary | GVHD- and Relapse- Free Survival by One Year Post Transplant | GVHD- and relapse- free survival will be defined as the absence of acute GVHD Grade III or IV or moderate or severe chronic GVHD or relapse or non-relapse mortality by one year post transplant. Acute GVHD will be diagnosed and graded according to Glucksberg criteria | Posted | Count of Participants | Participants | through study completion, an average of 1 year |
|
|
|
| 2 |
| 25 |
| 9 |
| 25 |
| 5 |
| 25 |
| EG001 | Methotrexate and Tacrolimus | The GVHD prophylaxis regimen on the standard of care arm will consist of methotrexate on Days +1,+3, +6 and +11 and tacrolimus Methotrexate: standard of care Methotrexate 5 mg/m2 on Days 1, 3, 6 and 11 Tacrolimus: Tacrolimus per institutional guidelines | 3 | 15 | 13 | 15 | 10 | 15 |
| Anemia | Blood and lymphatic system disorders | Systematic Assessment |
|
| CMV viremia | Infections and infestations | Systematic Assessment |
|
| Heart failure | Cardiac disorders | Systematic Assessment |
|
| hypotension | Cardiac disorders | Systematic Assessment |
|
| Lung infection | Infections and infestations | Systematic Assessment |
|
| Oral mucositis | Gastrointestinal disorders | Systematic Assessment |
|
| pericardial effusion | Cardiac disorders | Systematic Assessment |
|
| sepsis | Infections and infestations | Systematic Assessment |
|
| Skin rash | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| hemorrhagic cystitis | Renal and urinary disorders | Systematic Assessment |
|
| Acute kidney injury | Renal and urinary disorders | Systematic Assessment |
|
| C diff infection | Infections and infestations | Systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | Systematic Assessment |
|
| engraftment syndrome | Blood and lymphatic system disorders | Systematic Assessment |
|
| Headache | Nervous system disorders | Systematic Assessment |
|
| HLH | Blood and lymphatic system disorders | Systematic Assessment |
|
| hyperbilirubinemiα | Hepatobiliary disorders | Systematic Assessment |
|
| hyperglycemia | Endocrine disorders | Systematic Assessment |
|
| hypogammaglobulinemia | Blood and lymphatic system disorders | Systematic Assessment |
|
| hypokalemia | Renal and urinary disorders | Systematic Assessment |
|
| ischemic colitis and perforation | Gastrointestinal disorders | Systematic Assessment |
|
| cellulitis | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| thrombocytopenia | Blood and lymphatic system disorders | Systematic Assessment |
|
| PTLD | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Systematic Assessment |
|
| retinal detachment | Eye disorders | Systematic Assessment |
|
| volume overload | Renal and urinary disorders | Systematic Assessment |
|
| oral mucositis | Gastrointestinal disorders | Systematic Assessment |
|
| dry eyes | Eye disorders | Systematic Assessment |
|
| Acute kidney injury | Renal and urinary disorders | Systematic Assessment |
|
| BK viremia | Infections and infestations | Systematic Assessment |
|
| colitis | Gastrointestinal disorders | Systematic Assessment |
|
| fatigue | General disorders | Systematic Assessment |
|
| fever | Infections and infestations | Systematic Assessment |
|
| EBV viremia | Immune system disorders | Systematic Assessment |
|
| headache | Nervous system disorders | Systematic Assessment |
|
| nausea | Gastrointestinal disorders | Systematic Assessment |
|
| TTP | Blood and lymphatic system disorders | Systematic Assessment |
|
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| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D063088 | Phosphoramides |
| D009943 | Organophosphorus Compounds |
| D018796 | Immunoconjugates |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D012712 | Serum Globulins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D005916 | Globulins |
| D000630 | Aminopterin |
| D011622 | Pterins |
| D011621 | Pteridines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D018942 | Macrolides |
| D007783 | Lactones |