Reduced-Intensity Regimen Before Allogeneic Transplant for Patients With Relapsed Non-Hodgkin's or Hodgkin's Lymphoma

Eastern Cooperative Oncology Group

Status and phase: Terminated; Phase 2

Conditions: Lymphoma

Treatments: Procedure: Allogeneic bone marrow transplantation; Drug: Mycophenolate mofetil (MMF); Drug: Methotrexate (MTX); Procedure: Extracorporeal Photopheresis; Radiation: Total body irradiation (TBI); Drug: Pentostatin; Drug: Cyclosporin (CSA)

Study type: Interventional

Funder types: NETWORK; NIH

Identifiers

NCT00057954

E1402 (Other Identifier)

CDR0000285659

U10CA021115 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

RATIONALE: Photopheresis allows patient white blood cells to be treated with ultraviolet (UV) light and drugs outside the body to inactivate T cells. Pentostatin may suppress the immune system and reduce the chance of developing graft-versus-host disease (GVHD) following bone marrow transplantation. Combining photopheresis with pentostatin and total-body irradiation may be effective in killing cancer cells before bone marrow transplantation.

PURPOSE: This phase II trial is studying how well giving photophoresis together with pentostatin and total-body irradiation as a reduced-intensity regimen before allogeneic bone marrow transplantation works in treating patients with relapsed non-Hodgkin's or Hodgkin's lymphoma.

Full description

OBJECTIVES:

• Determine the rate of stable engraftment of donor cells in patients with relapsed non-Hodgkin's or Hodgkin's lymphoma treated with a reduced toxicity conditioning regimen followed by allogeneic (sibling or unrelated) bone marrow transplantation.
• Determine the extent and duration of acute and chronic graft-versus-host disease in patients treated with this regimen.
• Determine the 100-day overall survival and long-term progression-free survival of patients treated with this regimen.
• Evaluate the feasibility of collection of molecular chimerism studies at baseline, days 30, 100, 6 months and one and two years and at relapse.

OUTLINE: This is a multicenter study.

• Conditioning regimen: Patients undergo extracorporeal photopheresis using methoxsalen and UV light on 2 consecutive days between days -7 to -4. Patients receive pentostatin intravenously (IV) continuously on days -3 to -2 and undergo total body irradiation on day -1.
• Allogeneic bone marrow transplantation: Patients undergo infusion of allogeneic bone marrow or stem cells on day 0.
• Graft-versus-host disease prophylaxis: Patients receive oral or IV cyclosporine beginning on day -1 and continuing until 6 months after transplantation, oral mycofenolate mofetil beginning on day 100 and continuing for 1 year, and methotrexate IV on days 1 and 3.

Patients are followed at day 100, every 3 months for 1 year, every 6 months for 2 years, and then annually for 2 years.

PROJECTED ACCRUAL: A total of 36 patients will be accrued for this study within 1.8 years.

Enrollment: 6 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Non-Hodgkin's or Hodgkin's lymphoma that has relapsed following either a course of high dose chemotherapy or autologous stem cell transplantation.
• >= 90 days from prior transplant.
• Have a suitable human leukocyte antigen (HLA)-matched related bone marrow donor or a compatible matched unrelated bone marrow donor by molecular typing at HLA A, B, C, D, DR.
• Physically and psychologically capable of undergoing bone marrow transplantation and its attendant period of strict isolation.
• Age >= 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Be able to receive 400 cGy Total Body Irradiation (TBI).
• Pulmonary function tests: Diffusing capacity or Transfer factor of the lung for carbon monoxide (DLCO) >= 50% predicted, the forced expiratory volume in 1 second (FEV1) >= 50% predicted.
• Left ventricular ejection fraction (LVEF) at least 45% by Multi Gated Acquisition Scan (MUGA) or echocardiogram.
• Renal function: creatinine clearance > 50 ml/min.
• Liver function tests: < 3 x Upper Limit of Normal (ULN). Liver function test include serum glutamic oxaloacetic transaminase (SGOT) (Aspartate transaminase (AST)), Serum Glutamic Pyruvate Transaminase (SGPT) (Alanine transaminase (ALT)), and bilirubin.

Exclusion criteria

• Human immunodeficiency virus positive (HIV+) patients (test positive for P21 antibodies to HIV).
• Evidence of active infection (have received parenteral antibiotics <= 2 weeks prior to registration).
• Pregnant or breast-feeding women.
• Curable with any other therapeutic interventions.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

---

6 participants in 1 patient group

Transplant

Experimental group

Description:

Reduced toxicity conditioning regimen followed by allogeneic sibling or unrelated transplant. The conditioning regimen includes Extracorporeal Photopheresis, Pentostatin and total body irradiation (TBI). After allogeneic bone marrow transplantation, cyclosporin, mycophenolate mofetil (MMF), and methotrexate (MTX) will be given to prevent graft-versus-host disease (GVHD).

Treatment:

Drug: Cyclosporin (CSA)

Drug: Pentostatin

Radiation: Total body irradiation (TBI)

Procedure: Extracorporeal Photopheresis

Procedure: Allogeneic bone marrow transplantation

Drug: Methotrexate (MTX)

Drug: Mycophenolate mofetil (MMF)