Recruitment

Recruitment Status
Recruiting
Estimated Enrollment
Same as current

Summary

Conditions
  • Acute Leukemia
  • Hodgkin's Lymphoma
  • Multiple Myeloma
  • Myelodysplastic Syndrome
  • Non Hodgkin's Lymphoma
Type
Interventional
Phase
Phase 1Phase 2
Design
Allocation: Non-RandomizedIntervention Model: Sequential AssignmentMasking: None (Open Label)Primary Purpose: Treatment

Participation Requirements

Age
Between 18 years and 75 years
Gender
Both males and females

Description

Background: Graft versus host disease (GVHD) and impaired immune reconstitution are major transplant complications and barriers to improving outcomes after allogeneic hematopoietic stem cell transplantation (alloHSCT) for hematologic malignancies. GVHD is initiated when donor T-cells become alloreac...

Background: Graft versus host disease (GVHD) and impaired immune reconstitution are major transplant complications and barriers to improving outcomes after allogeneic hematopoietic stem cell transplantation (alloHSCT) for hematologic malignancies. GVHD is initiated when donor T-cells become alloreactive against recipient major or minor histocompatibility antigens. This process may be exacerbated during the transplantation process by exposure of tissue antigens to donor T-lymphocytes after chemotherapy-induced injury. Palifermin, a recombinant keratinocyte growth factor-1 (KGF-1), imitates the actions of intrinsic KGF and binds to the FGF receptor 2b, which is expressed in the epidermis, oral mucosa, GI mucosa and urothelium, thereby increasing the regenerative capacity of these tissues. Palifermin has been shown to reduce the duration and severity of oral mucositis after intensive chemo-radiotherapy and autologous HSCT for hematologic cancers and is FDA approved. In pre-clinical studies, palifermin has been shown to have an effect on control of acute or chronic GVHD and immune reconstitution after alloHSCT. However, subsequent clinical studies in alloHSCT indicate that the dose and schedule of palifermin as currently used in humans does not optimize its activity in terms of prevention of GVHD or thymus recovery following alloHSCT. - We hypothesize that higher doses of palifermin in the immediate pre alloHSCT conditioning setting will lead to enhanced thymopoiesis, decreased chronic GVHD, and improved immune reconstitution. A dose escalation study is necessary to determine safe dosing levels in persons undergoing alloHSCT. Objectives: The primary objective of the phase I portion is to assess the safety and tolerability of the administration of the recombinant keratinocyte growth factor (KGF) palifermin in alloHSCT using unrelated donor peripheral blood stem cells. The primary objective of the phase II portion is to determine the incidence of severe chronic GVHD after the addition of palifermin to TMS (tacrolimus, methotrexate and sirolimus) based GVHD prophylaxis delivered in the identical fashion to the NCI 07-C-0195 study. Eligibility: Adults (greater than or equal to 18 years) with advanced or high risk hematologic malignancies (including AML, ALL, MDS, CLL, NHL, HL, CML, multiple myeloma, and MPN)who lack a suitable HLA-matched sibling donor. An unrelated donor matched at a minimum of 8 alleles (HLA-A,-B,-C, and DRB1) by high-resolution typing, identified through the National Marrow Donor Program. Karnofsky greater than or equal to 60 and acceptable organ functions. Design: Patients will receive disease-specific induction chemotherapy (EPOCH-F/R or FLAG) prior to transplant as needed for disease control and immune depletion. All patients will receive an identical conditioning regimen consisting of cyclophosphamide 1200 mg/m^2/day IV for 4 days and fludarabine 30 mg/m^2/day for 4 days (transplant days -6 to -3). All patients will receive a peripheral blood stem cell product from an unrelated donor matched at HLA-A, -B, -C, -DRB1 (8/8) by high-resolution typing. Palifermin will be administered in a phase 1, open label design with the following proposed schedule: Dose level 1: 180 mcg/kg on day -7 Dose level 2: 360 mcg/kg on day -7 Dose level 3: 540 mcg/kg on day -7 Dose level 4: 720 mcg/kg on day -7 The phase I portion will be conducted in a standard 3+3 design; the maximum possible number of patients accrued to this portion will be 24. The maximum tolerated dose (MTD) from the phase I portion of the study will be used to conduct a phase II study. Total accrual on the phase II study will be 27 patients, including 3-6 patients treated at the MTD in the phase I portion of the study

Tracking Information

NCT #
NCT02356159
Collaborators
Not Provided
Investigators
Principal Investigator: Steven Z Pavletic, M.D. National Cancer Institute (NCI)