Ultra-Low Dose IL-2 Therapy as GVHD Prophylaxis in Haploidentical Allogeneic Stem Cell Transplantation

This is an interventional prevention trial for Acute Lymphoblastic Leukemia (ALL) focused on measuring Acute Lymphoblastic Leukemia (ALL), MDS, Chronic Myelogenous Leukemia (CML), Chronic Lymphocytic Leukemia (CLL), Acute Myelogenous Leukemia (AML) Read More

• 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.