Acute Myeloid Leukemia Clinical Trial
Official title:
Single Center Pilot Study to Investigate the Efficacy of Adding Itacitinib to Post-Transplant Cyclophosphamide as Graft-Versus-Host Disease Prophylaxis After Reduced Intensity Conditioning Matched Donor Hematopoietic Cell Transplantation With Peripheral Blood Stem Cells as Graft Source
Verified date | October 2023 |
Source | City of Hope Medical Center |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
This clinical trial evaluates the safety and effectiveness of adding itacitinib to cyclophosphamide and tacrolimus for the prevention of graft versus host disease (GVHD) in patients undergoing hematopoietic stem cell transplant. Itacitinib is an enzyme inhibitor that may regulate the development, proliferation, and activation of immune cells important for GVHD development. Cyclophosphamide and tacrolimus are immunosuppressive agents that may prevent GVHD in patients who receive stem cell transplants. Giving itacitinib in addition to cyclophosphamide and tacrolimus may be more effective at preventing GVHD in patients receiving hematopoietic stem cell transplants.
Status | Recruiting |
Enrollment | 50 |
Est. completion date | April 28, 2024 |
Est. primary completion date | April 28, 2024 |
Accepts healthy volunteers | No |
Gender | All |
Age group | N/A to 80 Years |
Eligibility | Inclusion Criteria: - Documented informed consent of the participant and/or legally authorized representative - Assent, when appropriate, will be obtained per institutional guidelines - Agreement to allow the use of archival tissue from diagnostic tumor biopsies - If unavailable, exceptions may be granted with study principal investigator (PI) approval - Age: =< 80 years - Note: Patients > 70 years of age must have Karnofsky performance status >= 80 and HCT-comorbidity index (CI) =< 2 - Karnofsky performance status >= 70% - Patients with the following diagnosis, eligible to undergo allogeneic HCT from an 8/8 match related/unrelated donor (A, B, C, DR by high resolution typing) - Acute leukemias (acute myeloid leukemia [AML] or acute lymphoblastic leukemia [ALL]) in complete remission with bone marrow (BM) blast of < 5% - Myelofibrosis (MF): Primary or secondary with high- or intermediate-2 risk per Dynamic International Prognostic Scoring System (DIPSS) - Myelodysplastic syndrome (blast < 10%) - Myeloproliferative neoplasm (MPN) other than MF needing HCT - Chronic myelomonocytic leukemia (CMML) - Total bilirubin =< 2 x upper limit of normal (ULN) (unless has Gilbert's disease) (within 30 days prior to day 1 of protocol therapy unless otherwise stated) - Serum glutamic-oxaloacetic transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) < 5 x ULN (within 30 days prior to day 1 of protocol therapy unless otherwise stated) - Creatinine clearance of >= 60 mL/min per 24 hour urine test or the Cockcroft-Gault formula (within 30 days prior to day 1 of protocol therapy unless otherwise stated) - Left ventricular ejection fraction (LVEF) >= 50% - Note: To be performed within 30 days prior to day 1 of protocol therapy - If able to perform pulmonary function tests: forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC) and diffusion capacity of the lungs for carbon monoxide (DLCO) (diffusion capacity) >= 50% of predicted (corrected for hemoglobin) (within 30 days prior to day 1 of protocol therapy) - If unable to perform pulmonary function tests: O2 saturation > 92% on room air (within 30 days prior to day 1 of protocol therapy) - Seronegative for human immunodeficiency virus (HIV) antigen (Ag)/antibody (Ab) combo, hepatitis C virus (HCV), active hepatitis B virus (HBV) (surface antigen negative), and syphilis rapid plasma reagin (RPR) (within 30 days prior to day 1 of protocol therapy) - If positive, hepatitis C ribonucleic acid (RNA) quantitation must be performed OR - If seropositive for HIV, HCV or HBV, nucleic acid quantitation must be performed. Viral load must be undetectable - Meets other institutional and federal requirements for infectious disease titer requirements - Note: Infectious disease testing to be performed within 28 days prior to day 1 of protocol therapy - Women of childbearing potential (WOCBP): negative urine or serum pregnancy test (within 30 days prior to day 1 of protocol therapy) - If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required - Agreement by females and males of childbearing potential to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least 6 months after the last dose of protocol therapy - Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for > 1 year (women only) Exclusion Criteria: - Prior allogeneic HCT - Chemotherapy, radiation therapy, biological therapy, immunotherapy within 21 days prior to day 1 of protocol therapy - Note: Conditioning regimen within 21 days prior to day 1 of protocol therapy is not considered as an exclusion criterion. Patients on maintenance chemotherapy are not excluded - Other investigational drugs for treatment of GVHD - History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agents - Psychological issues, no appropriate caregivers identified, or non-compliant to medication - Clinically significant uncontrolled illness - Uncontrolled infection (bacterial, viral, fungal) - Other active malignancy - Females only: Pregnant or breastfeeding - Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures - Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics) |
Country | Name | City | State |
---|---|---|---|
United States | City of Hope Medical Center | Duarte | California |
Lead Sponsor | Collaborator |
---|---|
City of Hope Medical Center | National Cancer Institute (NCI) |
United States,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Number of participants with Grade III-IV acute graft versus host disease (GVHD) | Acute GVHD will be graded and staged according to Mount Sinai Acute GVHD International Consortium (MAGIC) criteria. | By day 100 | |
Primary | GVHD-free relapse-free survival rate | Will be calculated using the Kaplan-Meier method. | From start of hematopoietic cell transplantation to grade III-IV acute GvHD, chronic GvHD requiring systemic treatment, relapse, or death (from any cause), whichever occurs first, assessed at 1 year | |
Secondary | Incidence of adverse events | The toxicity/adverse event information recorded on each subject will include type, severity, duration, and attribution/ association with the study regimen. Tables will be constructed to summarize the observed incidence, severity and type of toxicity, including infection. | Up to 2 years | |
Secondary | Overall survival | Will be calculated using the Kaplan-Meier method. | Day of stem cell infusion (day 0) until death or last follow-up, assessed at 100 days | |
Secondary | Overall survival | Will be calculated using the Kaplan-Meier method. | Day of stem cell infusion (day 0) until death or last follow-up, assessed at 180 days | |
Secondary | Overall survival | Will be calculated using the Kaplan-Meier method. | Day of stem cell infusion (day 0) until death or last follow-up, assessed at 1 year | |
Secondary | Progression free survival | Will be calculated using the Kaplan-Meier method. | From the date of stem cell infusion to the date of death, disease relapse/progression, or last follow-up, assessed at 100 days | |
Secondary | Progression free survival | Will be calculated using the Kaplan-Meier method. | From the date of stem cell infusion to the date of death, disease relapse/progression, or last follow-up, assessed at 180 days | |
Secondary | Progression free survival | Will be calculated using the Kaplan-Meier method. | From the date of stem cell infusion to the date of death, disease relapse/progression, or last follow-up, assessed at 1 year | |
Secondary | Relapse/progression | The cumulative incidence will be calculated using the competing risk method. | Day 0 to relapse/progression, assessed at 100 days | |
Secondary | Relapse/progression | The cumulative incidence will be calculated using the competing risk method. | Day 0 to relapse/progression, assessed at 180 days | |
Secondary | Relapse/progression | The cumulative incidence will be calculated using the competing risk method. | Day 0 to relapse/progression, assessed at 1 year | |
Secondary | Non-relapse mortality | The cumulative incidence will be calculated using the competing risk method. | Day 0 until non-disease related death or last follow-up, assessed at 100 days | |
Secondary | Non-relapse mortality | The cumulative incidence will be calculated using the competing risk method. | Day 0 until non-disease related death or last follow-up, assessed at 180 days | |
Secondary | Non-relapse mortality | The cumulative incidence will be calculated using the competing risk method. | Day 0 until non-disease related death or last follow-up, assessed at 1 year | |
Secondary | Rate of acute GVHD | Acute GVHD will be graded and staged according to MAGIC criteria. The first day of acute GVHD onset at a certain grade will be used to calculate the cumulative incidence (grades II-IV). The endpoint will be evaluated from day 0 through 100 days post-transplant. The cumulative incidence will be calculated using the competing risk method. | On day 100 | |
Secondary | Rate of chronic GVHD | Chronic graft versus host disease will be evaluated and scored according to National Institutes of Health Consensus Staging. The first day of chronic GVHD onset will be used to calculate the cumulative incidence. The cumulative incidence will be calculated using the competing risk method. | From day 80 through 1 year post-transplant | |
Secondary | Rate of infection | Microbiologically documented infections will be reported by site of disease, date of onset, severity and resolution, if any. This data will be captured via case report form and will be collected from day -7 to day 120 post-transplant and will follow the same data collection intervals as the toxicity and adverse event data. | Day -7 to day 120 | |
Secondary | Rate of hematologic recovery | Absolute neutrophil count >= 0.5 x 10^3/uL achieved and sustained for 3 consecutive lab values on different days with no subsequent decline.
Platelets >= 20 K/uL independent of platelet transfusion support (date should reflect no transfusions in previous 7 days, and the first of 3 consecutive lab values on different days). |
Up to 2 years | |
Secondary | Incidence of cytokine release syndrome | Defined and graded per American Society for Transplantation and Cellular Therapy criteria. | Up to 2 years | |
Secondary | Gut microbiome assessment | Gut microbiome diversity will be assessed by the inverse Simpson Index and compared among CBM588-treated/untreated patients; the inverse Simpson index is an ecological measure of a microbial diversity calculated by the inverse of the expected probability of 2 randomly selected bacterial sequences as belonging to the same operational taxonomic unit. | Up to 2 years |
Status | Clinical Trial | Phase | |
---|---|---|---|
Recruiting |
NCT05400122 -
Natural Killer (NK) Cells in Combination With Interleukin-2 (IL-2) and Transforming Growth Factor Beta (TGFbeta) Receptor I Inhibitor Vactosertib in Cancer
|
Phase 1 | |
Recruiting |
NCT04460235 -
Immunogenicity of an Anti-pneumococcal Combined Vaccination in Acute Leukemia or Lymphoma
|
Phase 4 | |
Completed |
NCT04022785 -
PLX51107 and Azacitidine in Treating Patients With Acute Myeloid Leukemia or Myelodysplastic Syndrome
|
Phase 1 | |
Completed |
NCT03678493 -
A Study of FMT in Patients With AML Allo HSCT in Recipients
|
Phase 2 | |
Recruiting |
NCT05424562 -
A Study to Assess Change in Disease State in Adult Participants With Acute Myeloid Leukemia (AML) Ineligible for Intensive Chemotherapy Receiving Oral Venetoclax Tablets in Canada
|
||
Completed |
NCT03197714 -
Clinical Trial of OPB-111077 in Patients With Relapsed or Refractory Acute Myeloid Leukaemia
|
Phase 1 | |
Terminated |
NCT03224819 -
Study of Emerfetamab (AMG 673) in Adults With Relapsed/Refractory Acute Myeloid Leukemia (AML)
|
Early Phase 1 | |
Active, not recruiting |
NCT03844048 -
An Extension Study of Venetoclax for Subjects Who Have Completed a Prior Venetoclax Clinical Trial
|
Phase 3 | |
Active, not recruiting |
NCT04070768 -
Study of the Safety and Efficacy of Gemtuzumab Ozogamicin (GO) and Venetoclax in Patients With Relapsed or Refractory CD33+ Acute Myeloid Leukemia:Big Ten Cancer Research Consortium BTCRC-AML17-113
|
Phase 1 | |
Active, not recruiting |
NCT04107727 -
Trial to Compare Efficacy and Safety of Chemotherapy/Quizartinib vs Chemotherapy/Placebo in Adults FMS-like Tyrosine Kinase 3 (FLT3) Wild-type Acute Myeloid Leukemia (AML)
|
Phase 2 | |
Recruiting |
NCT04920500 -
Bioequivalence of Daunorubicin Cytarabine Liposomes in Naive AML Patients
|
N/A | |
Recruiting |
NCT04385290 -
Combination of Midostaurin and Gemtuzumab Ozogamicin in First-line Standard Therapy for Acute Myeloid Leukemia (MOSAIC)
|
Phase 1/Phase 2 | |
Recruiting |
NCT03897127 -
Study of Standard Intensive Chemotherapy Versus Intensive Chemotherapy With CPX-351 in Adult Patients With Newly Diagnosed AML and Intermediate- or Adverse Genetics
|
Phase 3 | |
Active, not recruiting |
NCT04021368 -
RVU120 in Patients With Acute Myeloid Leukemia or High-risk Myelodysplastic Syndrome
|
Phase 1 | |
Recruiting |
NCT03665480 -
The Effect of G-CSF on MRD After Induction Therapy in Newly Diagnosed AML
|
Phase 2/Phase 3 | |
Completed |
NCT02485535 -
Selinexor in Treating Patients With Intermediate- and High-Risk Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome After Transplant
|
Phase 1 | |
Enrolling by invitation |
NCT04093570 -
A Study for Participants Who Participated in Prior Clinical Studies of ASTX727 (Standard Dose), With a Food Effect Substudy at Select Study Centers
|
Phase 2 | |
Recruiting |
NCT04069208 -
IA14 Induction in Young Acute Myeloid Leukemia
|
Phase 2 | |
Recruiting |
NCT05744739 -
Tomivosertib in Relapsed or Refractory Acute Myeloid Leukemia (AML)
|
Phase 1 | |
Recruiting |
NCT04969601 -
Anti-Covid-19 Vaccine in Children With Acute Leukemia and Their Siblings
|
Phase 1/Phase 2 |