Acute Myeloid Leukemia Clinical Trial
Official title:
A Dose Escalation Study of Intensity Modulated Total Marrow Irradiation (IMRT-TMI) Followed by Fludarabine as a Myeloablative Conditioning Regimen for Allogeneic Hematopoietic Stem Cell Transplantation for Patients With Relapsed and Refractory Hematologic Malignancies
Verified date | December 2023 |
Source | Indiana University |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
This is a phase I/II clinical trial to determine the maximum tolerated dose (MTD) of total marrow irradiation (TMI) followed by fludarabine in the context of a myeloablative conditioning regimen for allogeneic hematopoietic stem cell transplantation (allo-HSCT), as well as to determine the efficacy of the regimen in patients with high-risk leukemia and myelodysplasia.
Status | Withdrawn |
Enrollment | 0 |
Est. completion date | April 2029 |
Est. primary completion date | April 2027 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | Inclusion Criteria: 1. Documentation of Disease: Patients must be diagnosed with one of the following conditions: 1. Acute Myeloid Leukemia (AML), with no history of extramedullary disease, who are not in complete remission, who have either primary refractory or relapsed disease, and who do not have more than one of the following adverse factors: - Duration of first CR < 6 months (if previously in CR), based on the best overall clinical assessment of the disease course, not solely based on blood test or bone marrow biopsy results - Poor risk karyotype including any of the following: complex karyotype with =3 clonal abnormalities, 5q-/-5, 7q-/-7, 11q23 abnormalities, inv(3q), 20q or 21q abnormalities, t (6;9), t (9;22), 17p abnormalities [or TP53 mutations] or monosomal karyotype. Molecular typing (except for TP53 mutation) will not be used for eligibility criteria determination. - Circulating peripheral blood blasts at time of enrollment - Karnofsky performance status <90% 2. Acute Lymphocytic Leukemia (ALL) who are not in complete remission, who have either primary refractory or relapsed disease, and who do not have more than one of the following adverse factors: - Primary refractory or first relapse. Patients in second or subsequent relapse are excluded. - Bone marrow blasts >25% within 30 days before the start of the conditioning regimen - Age >40 years 3. Myelodysplasia with a Revised International Prognostic Score (IPSS-R) of greater than 4.5 (i.e., high- or very-high risk). 4. Chronic Myelogenous Leukemia (CML) in accelerated phase, defined by any of the following: - 10-19% blasts in peripheral blood white cells or bone marrow - Peripheral blood basophils at least 20% - Persistent thrombocytopenia (< 100 x 109/l) unrelated to therapy, or persistent thrombocytosis (>1000 x 109/l) unresponsive to therapy - Increasing spleen size and increasing white blood cell (WBC) count unresponsive to therapy - Cytogenetic evidence of clonal evolution (i.e., the appearance of an additional genetic abnormality that was not present in the initial specimen at the time of diagnosis of chronic phase) 2. The patient must be 18-65 years old at time of consent 3. Signed written informed consent: Patient must be capable of understanding the investigational nature of this study, potential risks and benefits of the study, and be able to provide a valid informed consent. 4. Availability of a consenting human leukocyte antigens (HLA)-matched donor 5. Karnofsky Performance Status 70% or higher 6. Required baseline laboratory values: - Estimated creatinine clearance = 60 ml/min - Aspartate aminotransferase and alanine aminotransferase = 2.5 x upper limit of normal value - Bilirubin = 1.5 x upper limit of normal value (unless determined to be related to Gilbert's disease) 7. Required baseline cardiac function values: - Required baseline cardiac function of left ventricular ejection fraction (LVEF) > 45 % corrected 8. Required baseline pulmonary function values: - Required baseline pulmonary function of lung diffusing capacity (DLCO) > 45 % predicted (corrected for hemoglobin)) Exclusion Criteria: 1. HIV seropositive patients 2. Pregnant or nursing females. 3. Prior radiation therapy 4. Patients who have had a prior autologous or allogeneic bone marrow or stem cell transplantation 5. Gemtuzumab ozogamicin (trade name: Mylotarg) and/or inotuzumab ozogamicin (trade name: Besponsa) use within 60 days before start of the conditioning regimen 6. Though this is NOT an exclusion criterion, we strongly recommend discontinuation of any steroidal oral contraceptives at least 7 days before start of the conditioning regimen. Use of therapeutic alternatives, including leuprolide should be considered to reduce the risk of SOS/VOD. Of note, for patients already on steroidal oral contraceptives for excessive menorrhagia, the switch to leuprolide should occur at least 2 weeks before the start of the conditioning regimen |
Country | Name | City | State |
---|---|---|---|
United States | Indiana University Melvin and Bren Simon Comprehensive Cancer Center | Indianapolis | Indiana |
Lead Sponsor | Collaborator |
---|---|
Naoyuki G. Saito, M.D., Ph.D. |
United States,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Maximum tolerated dose of Total Marrow Irradiation (TMI) followed by 150 mg/m2 fludarabine- Phase I only | Day -10 of conditioning regimen through 30 days post transplant (40 days) | ||
Primary | Overall survival (OS) rate 1 year post transplant-Phase II only | 1 year | ||
Secondary | Frequency of non hematologic toxicity | 100 days | ||
Secondary | Incidence of mucositis | 100 days | ||
Secondary | Incidence of acute graft versus host disease | 100 days | ||
Secondary | Incidence of chronic graft versus host disease | 100 days | ||
Secondary | Incidence of sinusoidal obstruction syndrome | 100 days | ||
Secondary | Incidence of pneumonitis | 100 days | ||
Secondary | Time to engraftment of neutrophils | rom date of transplant to the first of three consecutive days after transplantation during which the absolute neutrophil count (ANC) is greater than or equal to 0.5 x 10^9/liter | ||
Secondary | Time to engraftment of platelets | the time from Day 0 to the first of seven consecutive days after transplantation during which the platelet count is at least 20 x109/l without transfusion support. | ||
Secondary | Disease free survival | 3 years | ||
Secondary | Mean Quality of Life (QOL) as measured by Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) version 4 | 50 item likert type scale with responses measuring from 0-4 (where 0 = not at all; 1 = a little bit; 2 = somewhat, 3 = quite; and 4 = very much) with higher scores correlating to higher QOL | At screening, Day +30, Day +180, Day +365, Day +730 and Day +1095 from transplant (approximately 3 years) | |
Secondary | Incidence of non-relapse mortality | 30 days | ||
Secondary | Incidence of non-relapse mortality | 100 days | ||
Secondary | Incidence of non-relapse mortality | 1 year | ||
Secondary | Incidence of relapse mortality | 1 year | ||
Secondary | Incidence of relapse mortality | 30 days | ||
Secondary | Incidence of relapse mortality | 100 days | ||
Secondary | Overall Survival | Day +30, Day +100 and 1 year (approximately 3 years) |
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