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

NCT ID: NCT01374841

Last Updated: 2023-06-28

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-08-31
• Study Completion Date: 2023-12-31

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.

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.

Conditions

Hematologic Neoplasms

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Stem Cell Transplant+Cyclophosphamide

patients with high-risk hematologic malignancies will receive hematopoietic stem cell transplantation from haploidentical donors after treatment with cyclophosphamide

Group Type: EXPERIMENTAL

Cyclophosphamide

Intervention Type: DRUG

14.5 mg/kg, IV qd on day -6 and -5 and 50 mg/kg, IV on day +3 and +4

Hematopoietic Stem Cell Transplantation,

Intervention Type: OTHER

Hematopoietic Stem Cell Transplantation,

Interventions

Cyclophosphamide

14.5 mg/kg, IV qd on day -6 and -5 and 50 mg/kg, IV on day +3 and +4

Intervention Type: DRUG

Hematopoietic Stem Cell Transplantation,

Hematopoietic Stem Cell Transplantation,

Intervention Type: OTHER

Other Intervention Names

Endoxan; Stem cell transplantation

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

European Institute of Oncology

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Rocco Pastano, MD

Role: PRINCIPAL_INVESTIGATOR

European Institute of Oncology

Locations

European Institute of Oncology

Milan, , Italy

Site Status: RECRUITING

Countries

Italy

Central Contacts

Rocco Pastano, MD

Role: CONTACT

rocco.pastano@ieo.it

Facility Contacts

Rocco Pastano, MD

Role: primary

rocco.pastano@ieo.it

+390257489538

References

Luznik L, Jalla S, Engstrom LW, Iannone R, Fuchs EJ. Durable engraftment of major histocompatibility complex-incompatible cells after nonmyeloablative conditioning with fludarabine, low-dose total body irradiation, and posttransplantation cyclophosphamide. Blood. 2001 Dec 1;98(12):3456-64. doi: 10.1182/blood.v98.12.3456.

Reference Type: BACKGROUND

PMID: 11719388 (View on PubMed)

O'Donnell PV, Luznik L, Jones RJ, Vogelsang GB, Leffell MS, Phelps M, Rhubart P, Cowan K, Piantados S, Fuchs EJ. Nonmyeloablative bone marrow transplantation from partially HLA-mismatched related donors using posttransplantation cyclophosphamide. Biol Blood Marrow Transplant. 2002;8(7):377-86. doi: 10.1053/bbmt.2002.v8.pm12171484.

Reference Type: RESULT

PMID: 12171484 (View on PubMed)

Other Identifiers

2009-018083-94

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

IEO S513/110

Identifier Type: -

Identifier Source: org_study_id