Trial of Allogeneic Stem Cell Transplants From HLA Compatible, Related and Unrelated Donors After a Myeloablative Preparative Regimen With Hyperfractionated TBI, Thiotepa and Fludarabine For Adult Patients With Lymphohematopoietic Disorders

Leukemia Clinical Trial

Official title:

Phase II Trial of Allogeneic T-Cell Depleted Hematopoietic Stem Cell Transplants From HLA Compatible, Related and Unrelated Donors After a Myeloablative Preparative Regimen With Hyperfractionated TBI, Thiotepa and Fludarabine For Treatment of Adult Patients (>18 Years) With Lymphohematopoietic Disorders

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00587054
• Other study ID #: 01-070
• Secondary ID: CA23766CA33049
• Status: Completed
• Phase: Phase 2
• First received: December 21, 2007
• Last updated: May 17, 2011
• Start date: June 2001
• Est. completion date: May 2011

Study information

• Verified date: May 2011
• Source: Memorial Sloan Kettering Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

This is a phase II, single-center study to evaluate the efficacy of a novel cytoreductive regimen followed by CD34+E- selected T cell depleted allogeneic stem cell (or soybean agglutinated and E-rosetted BM) transplant as treatment for patients with acute and chronic leukemias, lymphoma and myelodysplstic syndrome/PNH. The impact of the change in conditioning regimen and use of CD34-selected T cell depleted PBSCs on transplanted related morbidity and mortality and disease free survival will be assessed.

Description:

The purpose of this study is: (1) to try to kill any cancer or precancer cells that are in your body, and to reduce the side effects of a transplant, which we have seen in our previous studies, (2) to see if this treatment with a new recipe of radiation and chemotherapy can suppress your immune system enough for the stem cells to 'take' and grow, (3) to see if the specially prepared stem cells can grow in you without a problem called graft-versus-host disease (GvHD) occurring.

One of the major side effects of any stem cell transplant is a condition known as graft vs. host disease or GVHD. GVHD is an immune reaction caused by certain cells from the transplanted stem cells called T-lymphocytes (or T-cells). The T-cells from your donor may see your organs as foreign and attack them. New ways to remove the T-cells from the stem cells before the transplant are being used to try and prevent GVHD. In some studies, the removal of T-cells from the stem cells has been successful for many patients in preventing both short-term (acute) and long-term (chronic) forms of GVHD. However, the removal of T-cells may increase the chance that the new bone marrow developing from the stem cells will be rejected or will not function well. Rejection of the transplant means that some of your own cells have survived the chemo and radiation therapy, and are attacking the new bone marrow cells. This condition can be lifethreatening because of an increased risk of infections and bleeding and would require your getting more treatment and additional stem cells. Studies like this one are designed to find better ways to avoid GVHD without increasing the risk of other problems such as graft rejection.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 129
• Est. completion date: May 2011
• Est. primary completion date: May 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

• Histologically proven acute or chronic leukemia, non Hodgkins and lymphoblastic lymphoma or myelodysplastic syndrome

• HLA 6/6 or 5/6 antigen matched related or unrelated donor

• creatinine = normal or if not, CrCl > 60 ml/min/1.73ml

• total bilirubin < 2.5, AST < 2xnl, cardiac function > 50%

• pulmonary function - asymptomatic or if not DLCO > %50% (corrected for Hgb)

• Karnofsky performance status > 70%

• negative pregnancy test (where applicable)

• signed informed consent of patient and donor.

Exclusion Criteria:

• Pregnancy or lactation

• unwillingness to comply with protocol treatment or follow-up

• uncontrolled infection

• HIV or HTLV positivity

• active CNS/skin disease

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Allogeneic Stem Cell Transplant
• Hemoglobinuria
• Hemoglobinuria, Paroxysmal
• Leukemia
• Lymphoblastic Lymphoma
• Lymphoma, Non-Hodgkin
• Myelodysplastic Syndrome
• Myelodysplastic Syndromes
• Non-Hodgkins
• Paroxysmal Nocturnal Hemoglobinuria (PNH)
• Preleukemia

Intervention

Drug:
• cytoreductive regimen followed by a CD34+E- selected allogeneic stem cell transplant
Myeloablative and will consist of hyperfractionated TBI - 1375 cGy administered in 11 doses of 125 cGy each over a total of four days, with three doses on three days and two doses on the last day, fludarabine 25 mg/m2 IV x 5 days, and thiotepa 5mg/kg IV x 2 days. Recipients of HLA identical related transplants will not receive ATG to promote engraftment. Recipients of HLA mismatched related or unrelated stem cells will receive ATG for two days prior to the transplant. G-CSF mobilized CD34+E- PBSCs obtained from the HLA compatible donor will be infused on day 0. Post transplantation G-CSF will be administered only if clinically indicated and should begin on or after d+7. Patients will be clinically evaluated at each clinic visit for incidence and severity of acute and chronic GVHD and transplant associated morbidity. Sequential evaluation of functional reconstitution of hematopoiesis and immunity will be made as per the BMT Service guidelines.
• cytoreductive regimen followed by a CD34+E- selected allogeneic stem cell transplant
Myeloablative and will consist of hyperfractionated TBI - 1375 cGy administered in 11 doses of 125 cGy each over a total of four days, with three doses on three days and two doses on the last day, fludarabine 25 mg/m2 IV x 5 days, and thiotepa 5mg/kg IV x 2 days. Recipients of HLA identical related transplants will not receive ATG to promote engraftment. Recipients of HLA mismatched related or unrelated stem cells will receive ATG for two days prior to the transplant. G-CSF mobilized CD34+E- PBSCs obtained from the HLA compatible donor will be infused on day 0. Post transplantation G-CSF will be administered only if clinically indicated and should begin on or after d+7. Patients will be clinically evaluated at each clinic visit for incidence and severity of acute and chronic GVHD and transplant associated morbidity. Sequential evaluation of functional reconstitution of hematopoiesis and immunity will be made as per the BMT Service guidelines.

Locations

Country	Name	City	State
United States	Memorial Sloan-Kettering Cancer Center	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
Memorial Sloan Kettering Cancer Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To evaluate the impact of a novel cytoreductive regimen followed by allogeneic stem cell transplant on transplant related morbidity and mortality.		3 years	Yes
Secondary	To estimate the disease-free and overall survival of patients in each disease group treated on this protocol; correlate progenitor cell dose and dose of clonable T cells with engraftment, chimerism, GVHD, and hematopoietic and immune reconstitution.		3 years	Yes

External Links

•   Memorial Sloan-Kettering web site