Clinical trial NCT01991457: Fludarabine / Total Body Irradiation Regimen for ALLO HCT in Acute Lymphoblastic Leukemia
Official title: Single Arm Phase II Study of Myeloablative Allogeneic Hematopoietic Stem Cell Transplantation for Acute Lymphoblastic Leukemia (ALL) in Older Patients Using Fludarabine and Total Body Irradiation (FluTBI) Regimen
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Adult Lymphoblastic Lymphoma
Keywords: ALL
Lead sponsor: University of Alabama at Birmingham
Sponsor class: OTHER
First posted: 2013-11-25
Enrollment: 19
Sex: ALL
Minimum age (years): 40
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of Subjects Disease-free Survival
timeFrame: 2 years post-transplant
Secondary outcomes:
measure: Percentage of Subjects That Survived
timeFrame: 2 years post-transplant
measure: Time to Neutrophil Engraftment
timeFrame: Within the first 100 days
measure: Number of Subjects With Regimen Related Toxicity
timeFrame: Within first 100 days post-transplant
measure: Percentage of Subjects With Acute GVHD
timeFrame: 2 years post transplant
measure: Number of Patients With Immune Reconstitution
timeFrame: 1 year post transplant
measure: Percentage of Subjects With Relapse
timeFrame: 2 Years post-transplant
measure: Number of Subjects With Platelet Engraftment
timeFrame: Within 100 days post transplant
measure: Percentage of Subjects With Chronic GVHD
timeFrame: 2 years post transplant
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: UAB Bone Marrow Transplantation and Cellular Therapy Program
state: Alabama
Study officials:
affiliation: University of Alabama at Birmingham
name: Omer H Jamy, MD
role: PRINCIPAL_INVESTIGATOR
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