Clinical Trials /

Hematopoietic Cell Transplantation for Patients With Hematologic Malignancies Using Related, HLA-Haploidentical Donors

NCT01374841

Description:

The purpose of this study is to determine if engraftment can be achieved safely in patients with high-risk hematologic malignancies who undergo non-myeloablative transplant with peripheral stem cells from Human Leukocyte Antigen (HLA) haploidentical donors with pre and post-transplant cyclophosphamide as immunosuppression.

Related Conditions:
  • Acute Lymphoblastic Leukemia
  • Acute Myeloid Leukemia
  • Chronic Lymphocytic Leukemia
  • Chronic Myeloid Leukemia
  • Hodgkin Lymphoma
  • Multiple Myeloma
  • Myelodysplastic Syndromes
  • Non-Hodgkin Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Hematopoietic Cell Transplantation for Patients With Hematologic Malignancies Using Related, HLA-Haploidentical Donors
  • Official Title: Nonmyeloablative Hematopoietic Stem Cell Transplantation (SCT) for High-Risk Hematologic Malignancies With Related, HLA-Haploidentical Donors: A Phase II Trial of Immunosuppression With Cyclophosphamide Administered Before and After SCT

Clinical Trial IDs

  • ORG STUDY ID: IEO S513/110
  • SECONDARY ID: 2009-018083-94
  • NCT ID: NCT01374841

Conditions

  • Hematologic Neoplasms

Interventions

DrugSynonymsArms
CyclophosphamideEndoxanStem Cell Transplant+Cyclophosphamide

Purpose

The purpose of this study is to determine if engraftment can be achieved safely in patients with high-risk hematologic malignancies who undergo non-myeloablative transplant with peripheral stem cells from Human Leukocyte Antigen (HLA) haploidentical donors with pre and post-transplant cyclophosphamide as immunosuppression.

Detailed Description

      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.
    

Trial Arms

NameTypeDescriptionInterventions
Stem Cell Transplant+CyclophosphamideExperimentalpatients with high-risk hematologic malignancies will receive hematopoietic stem cell transplantation from haploidentical donors after treatment with cyclophosphamide
  • Cyclophosphamide

Eligibility Criteria

        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
      
Maximum Eligible Age:70 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Donor engraftment
Time Frame:Day +84
Safety Issue:
Description:percentage of donor engraftment after 84 from baseline

Secondary Outcome Measures

Measure:Incidence and severity of graft versus host disease
Time Frame:up to 200 days after the baseline
Safety Issue:
Description:Incidence and severity of graft versus host disease after 200 days from the baseline
Measure:Non-relapse-related mortality
Time Frame:Incidence and severity of graft versus host disease after 200 days from the baseline
Safety Issue:
Description:incidence of non-relapse-related mortality after 200 days from the baseline

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:European Institute of Oncology

Trial Keywords

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

Last Updated

September 19, 2018