Adult Lymphoblastic Lymphoma
Conditions
Keywords
ALL
Brief summary
The goal of this research is to test if the conditioning regimen, fludarabine and total body irradiation (FluTBI), can lead to a safer and more effective stem cell transplant treatment regimen for ALL patients older than 40 years of age and/or younger patients with high risk medical conditions. The primary objective is to establish the efficacy of allo HCT in older ALL patients using myeloablative FluTBI conditioning regimen. The investigators are also assessing the safety and toxicity of allo HCT in older ALL patients using myeloablative FluTBI conditioning regimen.
Interventions
DRUGFludarabine
PROCEDURETotal Body Irradiation
Sponsors
University of Alabama at Birmingham
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
40 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Disease Criteria: * ALL in complete remission (CR) at the time of transplant. Remission is defined as less than 5.0% bone marrow lymphoblasts by morphology, as determined by a bone marrow aspirate obtained within 2 weeks of study registration. * Philadelphia chromosome positive ALL is allowed. * Lymphoid blastic crisis of CML will be included (provided that patients achieve CR). * Age Criteria: Equal or above age 40 and up to 65 years. If younger than 40, there must be comorbidities which preclude the patient to undergo CyTBI conditioning regimen. * Organ Function Criteria: All organ function testing should be done within 28 days of study registration. * Cardiac: Left ventricular ejection fraction (LVEF) ≥ 50% by MUGA (Multi Gated Acquisition) scan or echocardiogram. * Pulmonary: FEV1 (Forced expiratory volume in 1 second) and FVC (Forced vital capacity) ≥ 50% predicted, DLCO (alveolar diffusion capacity for carbon monoxide) (corrected for hemoglobin) ≥ 50% of predicted. * Renal: The estimated creatinine clearance (CrCl) must be equal or greater than 60 mL/min/1.73 m2 as calculated by the Cockcroft-Gault Formula: CrCl = (140-age) x weight (kg) x 0.85 (if female)/72 x serum creatinine (mg/dL). * Hepatic: * Serum bilirubin 2.0 g/dL * Aspartate transaminase (AST)/alanine transaminase (ALT) 2.5 ULN * Alkaline phosphatase 2.5 ULN * Performance status: Karnofsky ≥ 70% * Consent: Patient must be informed of the investigational nature of this study in accordance with institutional and federal guidelines and have the ability to provide written informed consent prior to initiation of any study-related procedures, and ability,in the opinion of the principal investigator, to comply with all the requirements of the study. * Presence of a willing adult HLA-matched sibling (excluding identical twin) or HLA-matched unrelated donor meeting all the criteria for routine allo HSCT. All donors will be evaluated for eligibility and suitability per the standard of care according to the FACT and NMDP guidelines.
Exclusion criteria
* Non-compliant to medications. * No appropriate caregivers identified. * HIV1 (Human Immunodeficiency Virus-1) or HIV2 positive * Active life-threatening cancer requiring treatment other than ALL * Uncontrolled medical or psychiatric disorders. * Uncontrolled infections, defined as positive blood cultures within 72 hours of study entry, or evidence of progressive infection by imaging studies such as chest CT scan within 14 days of registration. * Active central nervous system (CNS) leukemia * Preceding allogeneic HSCT * Receiving intensive chemotherapy within 21 days of registration. Maintenance type of chemotherapy will be allowed.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects Disease-free Survival | 2 years post-transplant | Percentage of patients without relapse of disease at 2 years |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Neutrophil Engraftment | Within the first 100 days | Neutrophil engraftment is defined as the first of 3 consecutive days with an absolute neutrophil count (ANC) \> 500/μL. Measuring the number of days it takes for (ANC) \> 500/μL. |
| Number of Subjects With Regimen Related Toxicity | Within first 100 days post-transplant | — |
| Percentage of Subjects With Acute GVHD | 2 years post transplant | — |
| Percentage of Subjects That Survived | 2 years post-transplant | — |
| Percentage of Subjects With Relapse | 2 Years post-transplant | — |
| Number of Subjects With Platelet Engraftment | Within 100 days post transplant | Platelet engraftment is defined as the first of 3 consecutive days with a platelet count \> 20,000/μL without platelet transfusion for 7 days. |
| Percentage of Subjects With Chronic GVHD | 2 years post transplant | — |
| Number of Patients With Immune Reconstitution | 1 year post transplant | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment Fludarabine, Total Body Irradiation (TBI)
Fludarabine
Total Body Irradiation | 19 |
| Total | 19 |
Baseline characteristics
| Characteristic | Treatment |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 19 Participants |
| Age, Continuous | 54 years |
| Race/Ethnicity, Customized Non-Hispanic White | 19 Participants |
| Region of Enrollment United States | 19 participants |
| Sex: Female, Male Female | 9 Participants |
| Sex: Female, Male Male | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 3 / 19 |
| other Total, other adverse events | 5 / 19 |
| serious Total, serious adverse events | 11 / 19 |
Outcome results
Primary
Percentage of Subjects Disease-free Survival
Percentage of patients without relapse of disease at 2 years
Time frame: 2 years post-transplant
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment | Percentage of Subjects Disease-free Survival | 63.2 percentage of participants |
Secondary
Number of Patients With Immune Reconstitution
Time frame: 1 year post transplant
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment | Number of Patients With Immune Reconstitution | 19 Participants |
Secondary
Number of Subjects With Platelet Engraftment
Platelet engraftment is defined as the first of 3 consecutive days with a platelet count \> 20,000/μL without platelet transfusion for 7 days.
Time frame: Within 100 days post transplant
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment | Number of Subjects With Platelet Engraftment | 19 Number of subjects with platelet engraft |
Secondary
Number of Subjects With Regimen Related Toxicity
Time frame: Within first 100 days post-transplant
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment | Number of Subjects With Regimen Related Toxicity | Acute kidney injury* | 4 participants |
| Treatment | Number of Subjects With Regimen Related Toxicity | Gastrointestinal (GI | 4 participants |
| Treatment | Number of Subjects With Regimen Related Toxicity | Mucositis | 3 participants |
Secondary
Percentage of Subjects That Survived
Time frame: 2 years post-transplant
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment | Percentage of Subjects That Survived | 68.4 Percentage of subjects that survived |
Secondary
Percentage of Subjects With Acute GVHD
Time frame: 2 years post transplant
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment | Percentage of Subjects With Acute GVHD | 26.1 percentage of aGVHD |
Secondary
Percentage of Subjects With Chronic GVHD
Time frame: 2 years post transplant
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment | Percentage of Subjects With Chronic GVHD | 32 Percentage of subjects with chronic GVHD |
Secondary
Percentage of Subjects With Relapse
Time frame: 2 Years post-transplant
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment | Percentage of Subjects With Relapse | 7.1 percentage of subjects with relapse |
Secondary
Time to Neutrophil Engraftment
Neutrophil engraftment is defined as the first of 3 consecutive days with an absolute neutrophil count (ANC) \> 500/μL. Measuring the number of days it takes for (ANC) \> 500/μL.
Time frame: Within the first 100 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment | Time to Neutrophil Engraftment | 12 days |