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Nonmyeloablative Hematopoietic Stem Cell Transplantation for High-Risk Hematologic Malignancies With Related, HLA-Haploidentical Donors: A Phase II Trial of Combined Immunosuppression With Cyclophosphamide Administered Before and After Transplantation.


Phase 2
18 Years
70 Years
Open (Enrolling)
Both
Hematologic Neoplasms

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Trial Information

Nonmyeloablative Hematopoietic Stem Cell Transplantation for High-Risk Hematologic Malignancies With Related, HLA-Haploidentical Donors: A Phase II Trial of Combined Immunosuppression With Cyclophosphamide Administered Before and After Transplantation.


It is important to extend the option of nonmyeloablative, hematopoietic stem cell
transplantation (HSCT) for potential therapy of hematologic malignancies to patients who do
not have an HLA-matched donor. Almost all patients would have a related donor identical for
one HLA haplotype (haploidentical) and mismatched at HLA-A, B or DR of the unshared
haplotype. Thus far, nonmyeloablative HSCT from HLA-mismatched donors has been associated
with a high rate of graft failure and graft-versus-host disease (GVHD). In this protocol, we
will use a combination of immunosuppressive agents including cyclophosphamide administered
before and after HSCT to facilitate engraftment and to delete highly alloreactive T-cell
clones presumably involved in GVHD.


Inclusion Criteria:



- Patients ≤70 years old

- Eligible diagnoses:

- CML in AP

- AML with high-risk cytogenetics [del(5q)/-5, del(7q)/-7, abnormal 3q, 9q, 11q, 20q,
21q, 17p, t(6:9), t(9;22), complex karyotypes (≥3 abnormalities)] in CR1

- AML ≥ CR2; patients should have <5% marrow blasts at the time of transplant

- High-risk ALL defined as:

CR1 with high-risk cytogenetics t(9;22), t(8;14), t(4;11), t(1;19) for adult patients >4
wk to achieve CR1

≥ CR2 Patients should have <5% marrow blasts at the time of transplant

- MDS (>int-1 per IPSS) after ≥ 1 prior cycle of induction chemotherapy; should have<5%
marrow blasts at the time of transplant

- MM Stage II or III patients who have progressed after an initial response to
chemotherapy or autologous HSCT or MM patients with refractory disease who may
benefit from tandem autologous-nonmyeloablative allogeneic transplant

- CLL, NHL or HD who are ineligible for autologous HSCT or who have
resistant/refractory disease and who may benefit from tandem autologous
nonmyeloablative allogeneic transplant.

- Patients who have received a prior allogeneic HSCT and who have either rejected their
grafts or who have become tolerant of their grafts with no active GvHD requiring
immunosuppressive therapy could be enrolled

Exclusion Criteria:

- Patients with suitably matched related or unrelated donors

- Patients with conventional transplant options (a conventional transplant should be
the priority for eligible patients ≤ 50 yr of age who have a related donor mismatched
for a single HLA-A, -B or DRB1 antigen)

- CNS involvement with disease refractory to intrathecal chemotherapy

- Presence of active, serious infection (e.g., mucormycosis, uncontrolled
aspergillosis, tuberculosis)

- Karnofsky Performance Status < 60% for adult patients (Appendix A)

- Patients with the following organ dysfunction:

- Left ventricular ejection fraction <35%

- DLCO <35% and/or receiving supplemental continuous oxygen

- Liver abnormalities: fulminant liver failure, cirrhosis of the liver with
evidence of portal hypertension, alcoholic hepatitis, esophageal varices,
hepatic encephalopathy, uncorrectable hepatic synthetic dysfunction as evidenced
by prolongation of the prothrombin time, ascites related to portal hypertension,
bacterial or fungal liver abscess, biliary obstruction, chronic viral hepatitis
with total serum bilirubin >3 mg/dL or symptomatic biliary disease.

- HIV-positive patients

- Women of childbearing potential who are pregnant (β-HCG+) or breast feeding

- Fertile men and women unwilling to use contraceptives during and for 12 months post
transplant

- Life expectancy severely limited by diseases other than malignancy

- Patients on any other investigational drug at time of enrolment

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Donor engraftment

Outcome Description:

percentage of donor engraftment after 84 from baseline

Outcome Time Frame:

Day +84

Safety Issue:

No

Principal Investigator

Rocco Pastano, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

European Institute of Oncology

Authority:

Italy: Ethics Committee

Study ID:

IEO S513/110

NCT ID:

NCT01374841

Start Date:

August 2010

Completion Date:

December 2019

Related Keywords:

  • Hematologic Neoplasms
  • Hematopoietic Stem Cell Transplantation
  • High-Risk Hematologic Neoplasms
  • Haploidentical Donors
  • Cyclophosphamide
  • Neoplasms
  • Hematologic Neoplasms

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