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

This study is currently recruiting participants.
Verified September 2012 by European Institute of Oncology
Sponsor:
Information provided by (Responsible Party):
European Institute of Oncology
ClinicalTrials.gov Identifier:
NCT01374841
First received: June 15, 2011
Last updated: September 10, 2012
Last verified: September 2012
  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.


Condition Intervention Phase
Hematologic Neoplasms
Drug: Cyclophosphamide
Other: Hematopoietic Stem Cell Transplantation,
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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.

Resource links provided by NLM:


Further study details as provided by European Institute of Oncology:

Primary Outcome Measures:
  • Donor engraftment [ Time Frame: Day +84 ] [ Designated as safety issue: No ]
    percentage of donor engraftment after 84 from baseline


Secondary Outcome Measures:
  • Incidence and severity of graft versus host disease [ Time Frame: up to 200 days after the baseline ] [ Designated as safety issue: Yes ]
    Incidence and severity of graft versus host disease after 200 days from the baseline

  • Non-relapse-related mortality [ Time Frame: Incidence and severity of graft versus host disease after 200 days from the baseline ] [ Designated as safety issue: Yes ]
    incidence of non-relapse-related mortality after 200 days from the baseline


Estimated Enrollment: 20
Study Start Date: August 2010
Estimated Study Completion Date: December 2019
Estimated Primary Completion Date: August 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01374841

Contacts
Contact: Rocco Pastano, MD rocco.pastano@ieo.it

Locations
Italy
European Institute of Oncology Recruiting
Milan, Italy, 20141
Contact: Rocco Pastano, MD    +390257489538    rocco.pastano@ieo.it   
Principal Investigator: Rocco Pastano, MD         
Sponsors and Collaborators
European Institute of Oncology
Investigators
Principal Investigator: Rocco Pastano, MD European Institute of Oncology
  More Information

Publications:
Responsible Party: European Institute of Oncology
ClinicalTrials.gov Identifier: NCT01374841     History of Changes
Other Study ID Numbers: IEO S513/110, 2009-018083-94
Study First Received: June 15, 2011
Last Updated: September 10, 2012
Health Authority: Italy: Ethics Committee
Italy: The Italian Medicines Agency

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

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

ClinicalTrials.gov processed this record on April 17, 2014