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
Study Details
Study Description
Brief 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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Transplant Patients
|
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.
|
Outcome Measures
Primary Outcome Measures
- Overall Survival of Transplant Patients [up to 6 years]
Calculate the median overall survival of transplant patients
Eligibility Criteria
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
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Memorial Sloan-Kettering Cancer Center | New York | New York | United States | 10065 |
Sponsors and Collaborators
- Memorial Sloan Kettering Cancer Center
- National Cancer Institute (NCI)
Investigators
- Principal Investigator: Ann Jakubowski, MD, Memorial Sloan Kettering Cancer Center
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- 01-070
- CA23766
- CA33049
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Transplant Patients |
|---|---|
| Arm/Group Description | Adult Patients (>18 years) with Lymphohematopoietic Disorders will receive Allogeneic T-Cell Depleted Hematopoietic Stem Cell Transplants After a Myeloablative Preparative Regimen With Hyperfractionated TBI, Thiotepa and Fludarabine |
| Period Title: Overall Study | |
| STARTED | 129 |
| COMPLETED | 120 |
| NOT COMPLETED | 9 |
Baseline Characteristics
| Arm/Group Title | Transplant Patients |
|---|---|
| Arm/Group Description | Adult Patients (>18 years) with Lymphohematopoietic Disorders will receive Allogeneic T-Cell Depleted Hematopoietic Stem Cell Transplants After a Myeloablative Preparative Regimen With Hyperfractionated TBI, Thiotepa and Fludarabine |
| Overall Participants | 129 |
| Age (Count of Participants) | |
| <=18 years |
2
1.6%
|
| Between 18 and 65 years |
127
98.4%
|
| >=65 years |
0
0%
|
| Sex: Female, Male (Count of Participants) | |
| Female |
51
39.5%
|
| Male |
78
60.5%
|
Outcome Measures
| Title | Overall Survival of Transplant Patients |
|---|---|
| Description | Calculate the median overall survival of transplant patients |
| Time Frame | up to 6 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Transplant Patients |
|---|---|
| Arm/Group Description | Adult Patients (>18 years) with Lymphohematopoietic Disorders will receive Allogeneic T-Cell Depleted Hematopoietic Stem Cell Transplants After a Myeloablative Preparative Regimen With Hyperfractionated TBI, Thiotepa and Fludarabine |
| Measure Participants | 120 |
| Median (Full Range) [Days] |
727.5
|
Adverse Events
| Time Frame | ||
|---|---|---|
| Adverse Event Reporting Description | ||
| Arm/Group Title | Transplant Patients | |
| Arm/Group Description | Adult Patients (>18 years) with Lymphohematopoietic Disorders will receive Allogeneic T-Cell Depleted Hematopoietic Stem Cell Transplants After a Myeloablative Preparative Regimen With Hyperfractionated TBI, Thiotepa and Fludarabine | |
All Cause Mortality |
||
| Transplant Patients | ||
| Affected / at Risk (%) | # Events | |
| Total | / (NaN) | |
Serious Adverse Events |
||
| Transplant Patients | ||
| Affected / at Risk (%) | # Events | |
| Total | 13/129 (10.1%) | |
| Blood and lymphatic system disorders | ||
| Hemorrhage, other | 1/129 (0.8%) | 1 |
| Cardiac disorders | ||
| Left ventricular failure | 1/129 (0.8%) | 1 |
| Eye disorders | ||
| Vision-double vision | 1/129 (0.8%) | 1 |
| General disorders | ||
| Constitutional symptoms, other | 4/129 (3.1%) | 4 |
| Infections and infestations | ||
| infection unknown absolut neutriphil counts | 1/129 (0.8%) | 1 |
| Infection without neutropenia | 3/129 (2.3%) | 3 |
| Musculoskeletal and connective tissue disorders | ||
| Hypoxia | 3/129 (2.3%) | 3 |
| Nervous system disorders | ||
| Leukoencephalopathy | 1/129 (0.8%) | 1 |
| Seizure | 1/129 (0.8%) | 2 |
| Renal and urinary disorders | ||
| Renal failure | 1/129 (0.8%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||
| Adult respiratory disorder | 1/129 (0.8%) | 1 |
| Skin and subcutaneous tissue disorders | ||
| Rash | 1/129 (0.8%) | 1 |
Other (Not Including Serious) Adverse Events |
||
| Transplant Patients | ||
| Affected / at Risk (%) | # Events | |
| Total | 126/129 (97.7%) | |
| Blood and lymphatic system disorders | ||
| Hemoglobin (Hgb) | 117/129 (90.7%) | 117 |
| Leukocytes | 125/129 (96.9%) | 125 |
| Lymphopenia | 125/129 (96.9%) | 125 |
| Neutrophils | 123/129 (95.3%) | 123 |
| Platelets | 124/129 (96.1%) | 124 |
| Prothrombin time (PT) | 11/129 (8.5%) | 11 |
| Partial thromboplastin time (PTT) | 22/129 (17.1%) | 22 |
| SGOT (AST) | 28/129 (21.7%) | 28 |
| SGPT (ALT) | 42/129 (32.6%) | 42 |
| Metabolism and nutrition disorders | ||
| Alkaline phosphatase | 23/129 (17.8%) | 23 |
| Bilirubin | 31/129 (24%) | 31 |
| Creatinine | 13/129 (10.1%) | 13 |
| Hyperglycemia | 58/129 (45%) | 58 |
| Hyperkalemia | 26/129 (20.2%) | 26 |
| Hypocalcemia | 35/129 (27.1%) | 35 |
| Hypokalemia | 60/129 (46.5%) | 60 |
| Hyponatremia | 35/129 (27.1%) | 35 |
| Hypophosphatemia | 48/129 (37.2%) | 48 |
Limitations/Caveats
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Dr. Ann Jakubowski |
|---|---|
| Organization | Memorial Sloan-Kettering Cancer Center |
| Phone | 212-639-5013 |
| jakubowa@mskcc.org |
- 01-070
- CA23766
- CA33049