Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| NCI-2015-02240 | Registry Identifier | University of California, San Francisco |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| Hellman Foundation | OTHER |
Not provided
Not provided
Not provided
The goal of this study is to determine whether post-transplant consolidation with azacitidine combined with donor lymphocyte infusion (DLI) is a safe and effective approach for the prevention of relapse in pediatric and young adult patients with hematologic malignancies who have undergone hematopoietic stem cell transplantation (HSCT).
This is a phase II single-arm trial of azacitidine (IV or SC) in combination with escalating donor lymphocyte infusion (DLI). Patients will be enrolled on the study by day +28 +/- 7 post-transplant, prior to withdrawal of immunosuppression or administration of donor lymphocyte infusion (DLI). They will have donor chimerism and minimal residual disease (MRD) testing from peripheral blood (PB) and bone marrow (BM) on day +28 ± 7. Patients will be stratified according to risk categories (low, standard and high), defined by GVHD status, mixed versus full donor chimerism, and positive versus negative MRD results. Depending on risk assessment, immunosuppression will be tapered according to standard or fast schedules, and patients (with the exception of low-risk ALL patients) will receive one cycle of low-dose azacitidine (40mg/m2 IV/SC daily x 4 days). After tapering immunosuppression, chimerism will be repeated and patients will receive up to 6 additional cycles of low-dose azacitidine, depending on risk assessment. For patients who meet criteria for high risk of relapse, azacitidine will be combined with escalating doses of DLI for a maximum of 7 cycles in total. Risk and safety assessments, including routine laboratory parameters, donor chimerism, minimal residual disease, and GHVD activity will be assessed following each cycle. Chimerism and minimal residual disease testing will be repeated every cycle by peripheral blood (PB), and bone marrow (BM) will be tested every other cycle. Patients will be followed by laboratory monitoring and physician evaluation prior to each cycle, and will be followed for two years post-transplant to study toxicity and GVHD outcomes.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Azacitidine/donor lymphocyte infusion | Experimental | Patients will be stratified according to risk categories (low, standard and high), defined by GVHD status, mixed versus full donor chimerism, and positive versus negative Minimal Residual Disease (MRD) results. Patients will receive up to 7 cycles of low-dose azacitidine (40mg/m2 IV/SC daily x 4 days) at 6 weekly intervals, except for low risk ALL patients who may not receive treatment after withdrawal of immunosuppression. Standard risk patients will receive an additional 6 cycles of azacitidine alone. High risk patients will receive an additional 6 cycles of azacitidine plus escalating DLI. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| azacitidine | Drug | 40mg/m2 IV/SC daily x 4 days, maximum of 7 cycles at 6 weekly intervals |
|
| Measure | Description | Time Frame |
|---|---|---|
| Relapse Rate | Relapse rate will be estimated using a percentage of participants who relapsed. It is assumed that the rate of relapse in pediatric acute leukemia post-transplant would be 40%, azacitidine +/- Donor Lymphocyte Infusion (DLI) would reduce the 2-year relapse rate by approximately 40% to a rate of 25%. | Up to 2 years |
| Frequency of System Specific Grade 3 or Higher Treatment-related Adverse Events | Frequency of system specific adverse events of interest include renal, hepatic, cardiac, pulmonary, or neurologic toxicities. Toxicities will be graded using NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. | Up to 2 years |
| Proportion of Participants With Acute and Chronic Graft Versus Host Disease (GVHD) | Proportion of participants with Grade 3-4 acute GVHD and moderate to severe chronic GVHD will be reported. | Up to 2 years |
| Proportion of Participants With Serious Infection | The proportion of participants will be reported for Grade 3-4 invasive fungal infection or disease caused by viral infections | Up to 2 years |
| Proportion of Participants With Severe Hematologic Toxicity Including Graft Failure | The proportion of participants will be reported for Grade 4 severe hematologic toxicities including graft failure | Up to 2 years |
| Number of Participants Whom Had >2 Dose Reductions for Any Reason | The number of participants whom had greater than 2 dose reductions for any reason. |
| Measure | Description | Time Frame |
|---|---|---|
| Median Relapse-free Survival | Release-free survival rate is defined as the median length of time after beginning treatment that the participant survives without progression or relapse, reported in months | Up to 2 years |
| Median Time to Relapse |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Christopher C Dvorak, M.D. | University of California, San Francisco | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of California San Francisco | San Francisco | California | 94143 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| Result | Justin T. Wahlstrom, Biljana N. Horn, Carol Fraser-Browne, Rebecca Hoeweler, Ying Lu, Alexis Melton, Jennifer Willert, Christopher C. Dvorak; Azacitidine Administration Following Hematopoietic Stem Cell Transplantation Is Safe and Feasible in Children with Acute Leukemia. Blood 2016; 128 (22): 4805. https://doi.org/10.1182/blood.V128.22.4805.4805 |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Azacitidine/Donor Lymphocyte Infusion | Patients will be stratified according to risk categories (low, standard and high), defined by GVHD status, mixed versus full donor chimerism, and positive versus negative Minimal Residual Disease (MRD) results. Patients will receive up to 7 cycles of low-dose azacitidine (40mg/m2 IV/SC daily x 4 days) at 6 weekly intervals, except for low risk ALL patients who may not receive treatment after withdrawal of immunosuppression. Standard risk patients will receive an additional 6 cycles of azacitidine alone. High risk patients will receive an additional 6 cycles of azacitidine plus escalating DLI. azacitidine: 40mg/m2 IV/SC daily x 4 days, maximum of 7 cycles at 6 weekly intervals donor lymphocyte infusion: For patients with cells available for DLI who are in the high risk group and do not have graft-versus-host disease (GVHD), DLI will be adminstered on day 5 of each cycle. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
Not provided
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| ICF | No | No | Yes | Informed Consent Form | May 5, 2015 | Jun 23, 2020 |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| donor lymphocyte infusion | Biological | For patients with cells available for DLI who are in the high risk group and do not have graft-versus-host disease (GVHD), DLI will be adminstered on day 5 of each cycle. |
|
| Up to 2 years |
Time to relapse is defined as the length of time after beginning treatment until the participant has experienced a relapse in disease, measured in months.
| Up to 2 years |
| COMPLETED |
|
| NOT COMPLETED |
|
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Azacitidine/Donor Lymphocyte Infusion | Patients will be stratified according to risk categories (low, standard and high), defined by GVHD status, mixed versus full donor chimerism, and positive versus negative Minimal Residual Disease (MRD) results. Patients will receive up to 7 cycles of low-dose azacitidine (40mg/m2 IV/SC daily x 4 days) at 6 weekly intervals, except for low risk ALL patients who may not receive treatment after withdrawal of immunosuppression. Standard risk patients will receive an additional 6 cycles of azacitidine alone. High risk patients will receive an additional 6 cycles of azacitidine plus escalating DLI. azacitidine: 40mg/m2 IV/SC daily x 4 days, maximum of 7 cycles at 6 weekly intervals donor lymphocyte infusion: For patients with cells available for DLI who are in the high risk group and do not have graft-versus-host disease (GVHD), DLI will be adminstered on day 5 of each cycle. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | 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 | Relapse Rate | Relapse rate will be estimated using a percentage of participants who relapsed. It is assumed that the rate of relapse in pediatric acute leukemia post-transplant would be 40%, azacitidine +/- Donor Lymphocyte Infusion (DLI) would reduce the 2-year relapse rate by approximately 40% to a rate of 25%. | Posted | Number | percentage of participants | Up to 2 years |
|
|
| |||||||||||||||||||||||||||
| Primary | Frequency of System Specific Grade 3 or Higher Treatment-related Adverse Events | Frequency of system specific adverse events of interest include renal, hepatic, cardiac, pulmonary, or neurologic toxicities. Toxicities will be graded using NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. | Posted | Count of Participants | Participants | Up to 2 years |
|
| ||||||||||||||||||||||||||||
| Primary | Proportion of Participants With Acute and Chronic Graft Versus Host Disease (GVHD) | Proportion of participants with Grade 3-4 acute GVHD and moderate to severe chronic GVHD will be reported. | Posted | Number | proportion of participants | Up to 2 years |
|
| ||||||||||||||||||||||||||||
| Primary | Proportion of Participants With Serious Infection | The proportion of participants will be reported for Grade 3-4 invasive fungal infection or disease caused by viral infections | Posted | Number | proportion of participants | Up to 2 years |
|
| ||||||||||||||||||||||||||||
| Primary | Proportion of Participants With Severe Hematologic Toxicity Including Graft Failure | The proportion of participants will be reported for Grade 4 severe hematologic toxicities including graft failure | No participants experienced a severe hematologic toxicity including graft failure | Posted | Number | proportion of participants | Up to 2 years |
|
| |||||||||||||||||||||||||||
| Primary | Number of Participants Whom Had >2 Dose Reductions for Any Reason | The number of participants whom had greater than 2 dose reductions for any reason. | Posted | Number | participants | Up to 2 years |
|
| ||||||||||||||||||||||||||||
| Secondary | Median Relapse-free Survival | Release-free survival rate is defined as the median length of time after beginning treatment that the participant survives without progression or relapse, reported in months | Posted | Median | Full Range | months | Up to 2 years |
|
| |||||||||||||||||||||||||||
| Secondary | Median Time to Relapse | Time to relapse is defined as the length of time after beginning treatment until the participant has experienced a relapse in disease, measured in months. | Posted | Median | Full Range | months | Up to 2 years |
|
|
Up to 2 years
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Azacitidine/Donor Lymphocyte Infusion | Patients will be stratified according to risk categories (low, standard and high), defined by GVHD status, mixed versus full donor chimerism, and positive versus negative Minimal Residual Disease (MRD) results. Patients will receive up to 7 cycles of low-dose azacitidine (40mg/m2 IV/SC daily x 4 days) at 6 weekly intervals, except for low risk ALL patients who may not receive treatment after withdrawal of immunosuppression. Standard risk patients will receive an additional 6 cycles of azacitidine alone. High risk patients will receive an additional 6 cycles of azacitidine plus escalating DLI. azacitidine: 40mg/m2 IV/SC daily x 4 days, maximum of 7 cycles at 6 weekly intervals donor lymphocyte infusion: For patients with cells available for DLI who are in the high risk group and do not have graft-versus-host disease (GVHD), DLI will be adminstered on day 5 of each cycle. | 0 | 17 | 10 | 17 | 17 | 17 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Rash maculo-papular | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Immune system disorders - Other | Immune system disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Fever | General disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Infections and infestations - Other | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
| |
| Musculoskeletal and connective tissue disorder - Other | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Edema face | General disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Diarrhea | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Cardiac disorders - Other | Cardiac disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Platelet count decreased | Investigations | CTCAE (4.0) | Systematic Assessment |
| |
| Hepatobiliary disorders - Other | Hepatobiliary disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Elevated transaminases | Investigations | CTCAE (4.0) | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Acute GVHD | Investigations | CTCAE (4.0) | Systematic Assessment |
| |
| Adrenal insufficiency | Endocrine disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Anisocoria | Eye disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Anxiety | Psychiatric disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Avascular necrosis | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Bacteremia | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
| |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Chest pain | General disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Cholestatic liver disease | Hepatobiliary disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Chronic GVHD | Investigations | CTCAE (4.0) | Systematic Assessment |
| |
| Chronic Pain | General disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Conductive Hearing Loss | Ear and labyrinth disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Cytomegalovirus (CMV) viremia | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
| |
| Depression | Psychiatric disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Electrolyte Abnormality | Investigations | CTCAE (4.0) | Systematic Assessment |
| |
| Emotional disturbance | Psychiatric disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Epileptic seizures | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Fever | General disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Foreskin adhesions | Reproductive system and breast disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Fracture | Injury, poisoning and procedural complications | CTCAE (4.0) | Systematic Assessment |
| |
| Cholecystitis | Hepatobiliary disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Headaches | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Hemorrhoids | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Human Herpesvirus 6 (HHV-6) viremia | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
| |
| Human Metapneumovirus (hMPV) | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
| |
| Hypertension | Vascular disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Hypomagnesemia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Iron overload | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Malnutrition | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Neuropathy | Vascular disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Osteopenia | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Pancytopenia | Blood and lymphatic system disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Post Transplant Immunodeficiency | Investigations | CTCAE (4.0) | Systematic Assessment |
| |
| Pseudoseizures | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Pulmonary aspergillosis | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
| |
| Weight Loss | Investigations | CTCAE (4.0) | Systematic Assessment |
| |
| Abnormal alanine aminotransferase (ALT) and aspartate aminotransferase (AST) | Investigations | CTCAE (4.0) | Systematic Assessment |
|
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Christopher Dvorak, MD | University of California, San Francisco | (415) 476-0554 | Christopher.Dvorak@ucsf.edu |
| ICF_000.pdf |
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Nov 17, 2016 | Jun 23, 2020 | Prot_SAP_001.pdf |
| ID | Term |
|---|---|
| D015470 | Leukemia, Myeloid, Acute |
| D054198 | Precursor Cell Lymphoblastic Leukemia-Lymphoma |
| D054429 | Leukemia, Myelomonocytic, Juvenile |
| D009190 | Myelodysplastic Syndromes |
| ID | Term |
|---|---|
| D007951 | Leukemia, Myeloid |
| D007938 | Leukemia |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D007945 | Leukemia, Lymphoid |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| D054437 | Myelodysplastic-Myeloproliferative Diseases |
| D001855 | Bone Marrow Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D001374 | Azacitidine |
| ID | Term |
|---|---|
| D001372 | Aza Compounds |
| D009930 | Organic Chemicals |
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| D012263 | Ribonucleosides |
Not provided
Not provided
| Title | Measurements |
|---|---|
|
| Unknown or Not Reported |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
|
|
|
|
|
|
|