Status:
COMPLETED
Ultra-Low Dose IL-2 Therapy as GVHD Prophylaxis in Haploidentical Allogeneic Stem Cell Transplantation
Lead Sponsor:
National Heart, Lung, and Blood Institute (NHLBI)
Conditions:
Acute Lymphoblastic Leukemia (ALL)
Acute Myelogenous Leukemia (AML)
Eligibility:
All Genders
18-75 years
Phase:
PHASE1
Brief Summary
Background: \- Stem cell transplantation from a partially matched donor can lead to graft-versus-host disease (GVHD). Researchers want to learn how to improve these transplantations. Objective: \- ...
Detailed Description
Although allogeneic stem cell transplantation (allo-SCT) is a curative option for many hematologic malignancies, not all have a suitable donor. Haploidentical peripheral blood stem cell transplantatio...
Eligibility Criteria
Inclusion
- INCLUSION CRITERIA RECIPIENT:
- Ages 18-70 years inclusive
- Haploidentical donor available
- Any one of the following hematologic conditions meeting a standard indication for allogeneic stem cell transplant:
- Chronic myelogenous leukemia (CML): Subjects under the age of 21 in chronic phase OR subjects ages 18-65 in chronic phase who have failed treatment with imatinib or have intolerance to imatinib OR Subjects ages 18-65 in accelerated phase or blast transformation. OR
- Acute lymphoblastic leukemia (ALL): any of these categories: Adult ALL including standard risk. All second or subsequent remissions, primary induction failure, partially responding or untreated relapse. OR
- Acute myelogenous leukemia (AML): AML in first remission - except AML with good risk karyotypes: AML M3 (t15; 17), AML M4Eo (inv 16), c-kit unmutated AML t (8; 21). All AML in second or subsequent remission, primary induction failure and resistant relapse. OR
- Myelodysplasticsyndromes(MDS): any of these categories - refractory anemia with transfusion dependence, refractory anemia with ANC\<500/ (Micro)L, refractory anemia with excess of blasts, transformation to acute leukemia, chronic myelomonocytic leukemia, atypical MDS/myeloproliferative syndromes. OR
- Myeloproliferative disorders including atypical (Ph-negative) chronic myeloid and neutrophilic leukemias, progressing myelofibrosis, and polycythemia vera, essential thrombocythemia either in transformation to acute leukemia or with progressive transfusion requirements or pancytopenia. OR
- Non-Hodgkin s lymphoma including Mantle cell lymphoma relapsing or refractory to standard of care treatments. OR
- Multiple myeloma, Waldenstroms macroglobulinemia, unresponsive or relapsed following standard of care treatments. OR
- Hodgkin's Lymphoma relapsing following an autologous transplant. OR
- Other rare hematologic malignancies for which hematopoietic stem cell transplantation has been performed and offers a durable remission or as the only option with a potential for cure.
- Chemotherapy-resistant multisystem Langerhans cell histiocytosis (MSLCH) especially involving organs like the bone marrow, liver, spleen, and lungs
- Aggressive systemic mastocytosis, and mast cell leukemia (MCL) in first CR (CR1)
- Hypereosinophilic syndrome who have failed imatinib therapy or FIP1L1-PDGFRa-negative patients who develop end-organ dysfunction
- Adult T-cell leukemia/lymphoma at first diagnosis
- Refractory or disseminated nasal-type extranodal NK/T-lymphoma or aggressive Natural killer cell leukemia/lymphoma
- Mycosis fungoides and S(SqrRoot)(Copyright)zary syndrome after failure of two or three initial therapies
- Primary or relapsed refractory Angioimmunoblastic T-cell lymphoma at first diagnosis
- Hepatosplenic T-cell lymphoma (gamma/delta T-cell lymphoma) at first diagnosis
- T-cell prolymphocytic leukemia at first diagnosis
- Subcutaneous panniculitic T-cell lymphoma at first diagnosis
- Hematodermic neoplasm (blastic natural killer cell lymphoma or Blastic plasmacytoid dendritic cell neoplasm) at first diagnosis
- Ability to comprehend the investigational nature of the study and provide informed consent.
- EXCLUSION CRITERIA RECIPIENT (ANY OF THE FOLLOWING):
- HLA identical (6/6) related or (8/8 allele level matched) unrelated donor available and readily accessible at time of transplantation evaluation
- Major anticipated illness or organ failure incompatible with survival from transplant
- Severe psychiatric illness or mental deficiency sufficiently severe as to make compliance with the transplant treatment unlikely and making informed consent impossible.
- Positive pregnancy test for women of childbearing age
- Contraindication to receive IL-2 including:
- Hypersensitivity to IL-2
- Sustained ventricular tachycardia (\>5 beats)
- Cardiac arrhythmias not controlled or unresponsive to management
- Chest pain with ECG changes, consistent with angina or myocardial infarction
- Cardiac tamponade
- Intubation for \>72 hours
- Renal failure requiring dialysis \>72 hours
- Coma or toxic psychosis lasting \> 48 hours
- Repetitive or difficult to control seizures
- Active bowel ischemia or perforation
- Active GI bleeding requiring surgery
- DLCO adjusted for Hb and ventilation\< 50% predicted
- Left ventricular ejection fraction \< 40% (evaluated by ECHO) or \< 30% (evaluated by MUGA)
- AST/SGOT \> 5 times ULN
- Total bilirubin \> 3 times ULN
- Estimated GFR \<60ml/min (calculated by CKD-EPI, a formula routinely used in Clinical Research Center at National Institutes of Health. In case of borderline estimated GFR, CKD-EPI creatinine-cystatin C formula will be used for more accurate estimation)
- Prior allogeneic stem cell transplantation
- INCLUSION CRITERIA DONOR:
- Related donor who shares 1 haplotype with the recipient
- Age greater than or equal to 18 or less than or equal to 80 years old
- Ability to comprehend the investigational nature of the study and provide informed consent.
- EXCLUSION CRITERIA DONOR (ANY OF THE FOLLOWING):
- Unfit to receive G-CSF and undergo apheresis such as abnormal blood counts, history of stroke, uncontrolled hypertension
- Sickling hemaglobinopathy including HbSS, HbAS, HbSC
- Donors who are positive for HIV, active hepatitis B (HBV), hepatitis C (HCV) or human T-cell lymphotropic virus (HTLV-I/II)
- Severe psychiatric illness. Mental deficiency sufficiently severe as to make compliance with the BMT treatment unlikely and making informed consent impossible.
Exclusion
Key Trial Info
Start Date :
August 26 2014
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
June 27 2018
Estimated Enrollment :
24 Patients enrolled
Trial Details
Trial ID
NCT02226861
Start Date
August 26 2014
End Date
June 27 2018
Last Update
July 5 2018
Active Locations (1)
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1
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892