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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT01374841
Recruitment Status : Recruiting
First Posted : June 16, 2011
Last Update Posted : September 20, 2018
Information provided by (Responsible Party):
European Institute of Oncology

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Hematologic Neoplasms Drug: Cyclophosphamide Other: Hematopoietic Stem Cell Transplantation, Phase 2

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.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Study Start Date : August 2010
Estimated Primary Completion Date : August 2019
Estimated Study Completion Date : December 2019

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Stem Cell Transplant+Cyclophosphamide
patients with high-risk hematologic malignancies will receive hematopoietic stem cell transplantation from haploidentical donors after treatment with cyclophosphamide
Drug: Cyclophosphamide
14.5 mg/kg, IV qd on day -6 and -5 and 50 mg/kg, IV on day +3 and +4
Other Name: Endoxan

Other: Hematopoietic Stem Cell Transplantation,
Hematopoietic Stem Cell Transplantation,
Other Name: Stem cell transplantation

Primary Outcome Measures :
  1. Donor engraftment [ Time Frame: Day +84 ]
    percentage of donor engraftment after 84 from baseline

Secondary Outcome Measures :
  1. Incidence and severity of graft versus host disease [ Time Frame: up to 200 days after the baseline ]
    Incidence and severity of graft versus host disease after 200 days from the baseline

  2. Non-relapse-related mortality [ Time Frame: Incidence and severity of graft versus host disease after 200 days from the baseline ]
    incidence of non-relapse-related mortality after 200 days from the baseline

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01374841

Contact: Rocco Pastano, MD

European Institute of Oncology Recruiting
Milan, Italy, 20141
Contact: Rocco Pastano, MD    +390257489538   
Principal Investigator: Rocco Pastano, MD         
Sponsors and Collaborators
European Institute of Oncology
Principal Investigator: Rocco Pastano, MD European Institute of Oncology

Publications of Results:
Other Publications:
Responsible Party: European Institute of Oncology Identifier: NCT01374841     History of Changes
Other Study ID Numbers: IEO S513/110
2009-018083-94 ( EudraCT Number )
First Posted: June 16, 2011    Key Record Dates
Last Update Posted: September 20, 2018
Last Verified: September 2018

Keywords provided by European Institute of Oncology:
Hematopoietic Stem Cell Transplantation
High-Risk Hematologic Neoplasms
Haploidentical Donors

Additional relevant MeSH terms:
Hematologic Neoplasms
Neoplasms by Site
Hematologic Diseases
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists