Safety and Efficacy of Pentostatin and Low Dose TBI With Allogenic Peripheral Blood Stem Cell Transplant

• Status: Completed
• Trial end date: 2008-12-01
• Target enrollment: 0
• Participant gender: All

Summary

This is a continuation of a pilot study which is now regarded as a phase II trial with a plan to enroll an additional 40 patients (20 related and 20 unrelated donor transplants) with hematological malignancy assessing the safety and efficacy of a minimally myelosuppressive regimen with pentostatin and low-dose total body irradiation (TBI) followed by allogeneic peripheral blood stem cell transplantation (alloPSCT).

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Nebraska
• Collaborators: Astex Pharmaceuticals; Astex Pharmaceuticals, Inc.
• Treatments: Cyclosporine; Cyclosporins; Mycophenolate mofetil; Mycophenolic Acid; Pentostatin

Criteria

Inclusion Criteria:

Age 19-75 years

1. Patients who relapse after autologous stem cell transplantation.

2. Patients who are candidates for an autologous or conventional allogeneic stem cell transplantation from a disease standpoint but who do not qualify functionally (from the point of view of organ function, or performance status) for a myeloablative protocol.

3. Any patient, where in the opinion of the primary treating oncologist, nonmyleoablative therapy would be the treatment option in the best patients interest providing the patient fits all other eligibility criteria for this protocol.

Identification of a matched related or unrelated stem cell donor

Diseases:

Acute myelogenous leukemia first complete remission with high-risk cytogenetics>second complete remission minimal residual disease (<10% blasts*). Acute lymphocytic leukemia first complete remission with high-risk cytogenetics >second complete remission minimal residual disease (<10% blasts*). Chronic myelogenous leukemia first chronic phase, accelerated phase (<10% blasts*)blast phase with minimal residual disease (<10% blasts*)second chronic phase. Chronic lymphocytic leukemia recurrence after the front line regimen (related donor transplant), chemorefractory disease (unrelated donor transplant),T-CLL in partial remission or any minimal residual disease. Myelodysplastic syndromes refractory anemia with or without ringed sideroblasts,RAEB, RAEB-T, and CMML (< than 10% blasts*). *both in peripheral blood and bone marrow

Multiple myeloma - after receiving at least one regimen of prior chemotherapy

Non-Hodgkin's Lymphomas:

Small Lympho(plasma)cytic Lymphoma (B-SLL, B-LPL): recurrence after a front line regimen (related donor transplant), or chemorefractory disease (related or unrelated donor transplant). Follicular Low-Grade Lymphoma, Marginal Zone Lymphomas (splenic, nodal, or extranodal/MALT type): chemorefractory disease or > 2 prior regimens. Mantle Cell Lymphoma: first complete or partial remission, refractory disease, or failed prior ASCT. Diffuse Large B-cell Lymphoma, Follicular Large cell Lymphoma, Peripheral T-cell Lymphoma, Anaplastic Large Cell Lymphoma: refractory disease, or failed prior ASCT. Burkitt or Acute Lymphoblastic Lymphomas: high-risk disease in remission, chemosensitive persistent or recurrent disease. Cutaneous T-cell Lymphomas: (Mycosis Fungoides, Sezary Syndrome): chemorefractory disease of > 2 prior regimens

Hodgkins Disease: refractory or persistent disease and not candidate for ASCT, or failed prior ASCT.

Peripheral T-cell Lymphoma

Exclusion Criteria:

• Age > 75 years and < 19 years

• progressive disease within 8 weeks of prior therapy or within 12 weeks after prior autologous stem cell transplantation

• Active CNS malignancy (patients with known positive CSF cytology or parenchymal lesions visible by CT or MRI)

• Fertile men or women unwilling to use appropriate contraceptive techniques during and for 12 months following treatment

• Females who are pregnant

• Patients who are HIV seropositive

• Active uncontrolled infection or immediate life-threatening condition at the time of enrollment

• Significant Organ dysfunction:

1. Calculated Creatinine Clearance <55ml/min

2. cardiac ejection fraction <40%, NYHA class II or greater cardiac disease.

3. DLCO < 40% , FEV1/FVC ratio <50% predicted, or receiving supplementary continuous oxygen

4. total bilirubin > 2x upper limit of normal (unless due to Gilberts disease or malignancy), ALT and AST 4x the upper limit of normal

• Karnofsky score <60%

• Patients with uncontrolled medical illnesses (e.g., uncontrolled systemic hypertension, diabetes)

Donor Inclusion Criteria:

• HLA genotypically matched relative

• siblings or first-degree relatives matched at HLA-A, B, or DR loci (6 antigen match) are acceptable donors

• HLA matched unrelated volunteer donor

• unrelated donor matched at HLA-A, B, or DR loci (6 antigen match) are acceptable donors

• One antigen mismatch related or unrelated donor will also be acceptable, molecular typing needs to be used at each H LA-A, B, or DR loci in case of mismatched unrelated donor.

Donor Exclusion Criteria:

• Identical twin

• Pregnancy

• HIV positive

• Serious Allergy to G-CSF

• Current serious systemic illness

• Failure to meet the UNMC or NMDP criteria for donors