CONDITIONING REGIMENS: Patients with high-risk leukemia will receive myeloablative
conditioning with anti-thymocyte globulin intravenously (IV) over 4-6 hours on days -12
through -9, Fludarabine IV over 30 minutes on days -8 through -5, Thiotepa IV every every 12
hours on day -4 and Total Body Irradiation (TBI) on days -3 through -1. All other patients
receive reduced intensity conditioning consisting of anti-thymocyte globulin intravenously
(IV) over 4-6 hours on days -12 through -9, fludarabine IV over 30 minutes on days -8 through
-5, thiotepa IV over 4 hours every 12 hours on day -4, and melphalan IV on days -3 and -2.
PERIPHERAL BLOOD STEM CELL TRANSPLANTATION: Patients undergo TCR-alpha/beta+ and CD19+
depleted KIR/KIR ligand-mismatched haploidentical donor peripheral blood stem cell
transplantation on day 0. If the graft contains less than 4 x 10^6 CD34+ cells/kg, a second
HSC graft may be administered.
PROPHYLAXIS FOR GVHD: Patients receiving a graft containing > 25 x 10^3 CD3+ TCR alpha/beta+
cells receive mycophenolate mofetil IV twice daily over 2 hours on days 1 to 30 with a rapid
taper. Patients with TCR alpha/beta+ cells exceeding 100,000/kg also receive tacrolimus IV
continuously or orally (PO) every 12 hours on days 0-90 with a taper at the discretion of the
Principal Investigator.
ZOLEDRONATE ADMINISTRATION: Patients will receive five doses of Zoledronate (IV) at 28 day
intervals beginning on Day +28 post-HSCT.
Follow-up assessments will occur after transplantation.
Inclusion Criteria:
- Availability of an eligible haploidentical donor
- Hematologic malignancy or solid tumor
- Patients with more than one malignancy (hematologic or solid tumor) are eligible
- Patients with hematologic malignancy must have no HLA identical sibling or suitable
unrelated donor OR time needed to find an acceptable unrelated donor match would
likely result in disease progression such that the patient may become ineligible for
any type of potentially curative transplant
- Relapsed or primary therapy-refractory AML with bone marrow blast < 20%
- High-risk refractory or relapsed ALL in patients for whom transplantation is
deemed indicated (relapse occurring < 30 months from diagnosis, patients
relapsing after previous allogeneic transplant, relapse after 2nd remission,
primary induction failure or hypodiploidy)
- Relapsed Hodgkin lymphoma unable to achieve 2nd remission or Very Good Partial
Response (VGPR) and therefore ineligible to receive autologous hematopoietic stem
cell transplant (auto-HSCT)
- Hodgkin lymphoma relapsing after auto-HSCT
- Primary refractory or relapsed non-Hodgkin lymphoma unable to achieve 2nd
remission or VGPR and therefore ineligible to receive auto-HSCT
- Non-Hodgkin lymphoma relapsing after auto-HSCT
- Myelodysplastic Syndrome/Myeloproliferative Syndrome
Solid Tumor
- Patients with solid tumor must have failed or have been ineligible to receive
auto-HSCT or if auto-HSCT would not offer > 20% chance of cure
- Neuroblastoma
- high risk with relapsed or refractory disease
- Soft tissue sarcomas (Rhabdomyosarcoma, Ewing sarcoma, Primitive Neuroectodermal Tumor
or other high-risk extracranial solid tumors)
- Relapsed or primary refractory metastatic
- 1st complete remission, but very high-risk features (i.e., < 20% survival with
conventional therapy)
- Osteosarcoma
- Failure to achieve Complete Response (CR) following initial therapy
- Relapsed with pulmonary or bone metastases and did not achieve a CR with surgery
and/or chemotherapy
- Karnofsky (patients > 16 years) or Lansky (patients 16 years or older) performance
score of ≥ 60
- Life expectancy of ≥ 3 months
- Patient must have fully recovered from acute toxic effects of all prior chemotherapy,
immunotherapy, or radiotherapy prior to entering this study
- Study enrollment no earlier than 3 months after preceding HSCT
- Glomerular Filtration Rate (GFR) ≥ 60 ml/min/1.73m2
- Total bilirubin < 3 mg/dL
- ALT (alanine aminotransferase, SCPT) ≤ 5 x Upper LImit of Normal (ULN) for age
- Ejection fraction of > 40% by Multigated Acquisition Scan (MUGA) or echocardiogram
- No evidence of dyspnea at rest
- No supplemental oxygen requirement
- If measured, carbon monoxide diffusion capacity (DLCO) >50%
- No severe peripheral neuropathy, signs of leukoencephalopathy or active Central
Nervous System (CNS) infection
- Patients with seizure disorders may be enrolled if seizures are well controlled on
anticonvulsant therapy
- If of reproductive potential, negative pregnancy test and willing to use effective
birth control method
- Informed consent from patient or legal guardian (if patient is minor)
Inclusion Criteria for Donors:
- Donor must be 18 years of age minimum, 65 years of age maximum
- Donor must be in good general health as determined by evaluating medical provider
- Must meet donor criteria for human cells, tissues, and cellular and tissue-based
products per Code of Federal Regulations 21 CFR 1271, subpart C. Specifically:
- Donor screening in accordance with 1271.75 indicates that the donor:
- Is free from risk factors for, and clinical evidence of, infection due to
relevant communicable disease agents and diseases; and
- Is free from communicable disease risks associated with xenotransplantation;
and
- The results of donor testing for relevant communicable disease agents in
accordance with 1271.80 and 1271.85 are negative or nonreactive, except as
provided in 1271.80(d)(1).
- Haploidentical by HLA-typing
- Preference will be given to donors who demonstrate KIR incompatibility with recipient
HLA class I ligands defined as the donor expressing a KIR gene for which the
corresponding HLA class I ligand is not expressed by the recipient.
- Negative testing for relevant communicable diseases:
- Hepatitis B surface antigen (HBsAg)
- Hepatitis B core antibody (Anti-HBc)
- Hepatitis C antibody (Anti-HCV)
- HIV 1 & 2 antibody (Anti-HIV-1, 2 plus O)
- HTLV I/II antibody (Anti-HTLV I/II)
- RPR (Syphilis TP)
- CMV (Capture CMV)
- MPX for: HepB (HBV-PCR), HepC (HCV-PCR), HIV (HIV-PCR)
- NAT for West Nile Virus (WNV-PCR)
- T. Cruzi - EIA (Chagas)
Exclusion Criteria:
- Pregnant or breast-feeding
- HIV infection
- Heart failure or uncontrolled cardiac rhythm disturbance
- Uncontrolled, Serious Active Infection
- Prior organ allograft
- Significant serious intercurrent illness unrelated to cancer or its treatment not
covered by other exclusion criteria expected to significantly increase the risk of
HSCT
- Any mental or physical condition, in the opinion of the PI (or PI designee), which
could interfere with the ability of the subject (or the only parent or legal guardian
available to care for the subject) to understand or adhere to the requirements of the
study
- Enrollment in any other clinical study from screening up to Day 100 (unless PI judges
such enrollment would not interfere with endpoints of this study)
Exclusion Criteria for Donors:
- Lactating females
- Pregnant females
