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

NCT01374841 | Unknown Phase 2

• 2 other identifiers: IEO S513/1102009-018083-94
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Hematologic Neoplasms

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Donor engraftment

  percentage of donor engraftment after 84 from baseline

  Day +84

Secondary Outcomes (2)

• Incidence and severity of graft versus host disease

  up to 200 days after the baseline

• Non-relapse-related mortality

  Incidence and severity of graft versus host disease after 200 days from the baseline

Study Arms (1)

Stem Cell Transplant+Cyclophosphamide

EXPERIMENTAL

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

Drug: Cyclophosphamide; Other: Hematopoietic Stem Cell Transplantation,

Interventions

Cyclophosphamide DRUG

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

Also known as: Endoxan

Stem Cell Transplant+Cyclophosphamide

Hematopoietic Stem Cell Transplantation, OTHER

Hematopoietic Stem Cell Transplantation,

Also known as: Stem cell transplantation

Stem Cell Transplant+Cyclophosphamide

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• European Institute of Oncology: lead

Study Sites (1)

European Institute of Oncology

Milan, 20141, Italy

RECRUITING

Related Publications (2)

• 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.

  PMID: 11719388 BACKGROUND

• 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.

  PMID: 12171484 RESULT

MeSH Terms

Conditions

Hematologic Neoplasms

Interventions

Cyclophosphamide; Hematopoietic Stem Cell Transplantation; Stem Cell Transplantation

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative

Study Officials

• Rocco Pastano, MD

  European Institute of Oncology

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Rocco Pastano, MD

CONTACT

rocco.pastano@ieo.it

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 15, 2011
• First Posted: June 16, 2011
• Study Start: August 1, 2010
• Primary Completion: December 1, 2023
• Study Completion: December 1, 2023
• Last Updated: June 28, 2023

Record last verified: 2023-06

Locations

IT (1)