Trial record 15 of 39 for:    "Paroxysmal nocturnal hemoglobinuria"

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

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT00587054
First received: December 21, 2007
Last updated: May 17, 2011
Last verified: May 2011
  Purpose

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.


Condition Intervention Phase
Allogeneic Stem Cell Transplant
Leukemia
Non-Hodgkins
Lymphoblastic Lymphoma
Myelodysplastic Syndrome
Paroxysmal Nocturnal Hemoglobinuria (PNH)
Drug: cytoreductive regimen followed by a CD34+E- selected allogeneic stem cell transplant
Phase 2

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

Resource links provided by NLM:


Further study details as provided by Memorial Sloan-Kettering Cancer Center:

Primary Outcome Measures:
  • To evaluate the impact of a novel cytoreductive regimen followed by allogeneic stem cell transplant on transplant related morbidity and mortality. [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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. [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]

Enrollment: 129
Study Start Date: June 2001
Study Completion Date: May 2011
Primary Completion Date: May 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
6/6 HLA matched, related donors
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.

Experimental: 2
5/6 HLA compatible related plus 5/6 and 6/6 HLA compatible unrelated donors
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.


Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00587054

Locations
United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10065
Sponsors and Collaborators
Memorial Sloan-Kettering Cancer Center
Investigators
Principal Investigator: Ann Jakubowski, MD Memorial Sloan-Kettering Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Ann Jakubowski, MD, Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT00587054     History of Changes
Other Study ID Numbers: 01-070, CA23766, CA33049
Study First Received: December 21, 2007
Last Updated: May 17, 2011
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Memorial Sloan-Kettering Cancer Center:
leukemia
non-Hodgkins
lymphoblastic lymphoma
myelodysplastic syndrome
paroxysmal nocturnal hemoglobinuria (PNH)
cytoreductive regimen
allogeneic stem cell transplant

Additional relevant MeSH terms:
Hemoglobinuria
Leukemia
Lymphoma
Hemoglobinuria, Paroxysmal
Myelodysplastic Syndromes
Preleukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Lymphoma, Non-Hodgkin
Proteinuria
Urination Disorders
Urologic Diseases
Urological Manifestations
Signs and Symptoms
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Anemia, Hemolytic
Anemia
Hematologic Diseases
Bone Marrow Diseases
Precancerous Conditions
Leukemia, Lymphoid
Thiotepa
Fludarabine
Fludarabine monophosphate
Antineoplastic Agents, Alkylating
Alkylating Agents

ClinicalTrials.gov processed this record on July 20, 2014