Phase 2 N=50 Treatment

Stem Cell Transplantation and T-Cell Add-Back to Treat Bone Marrow Malignancies

Hematologic Malignancies · Bone Marrow Transplant Rejection

Bottom Line

View on ClinicalTrials.gov: NCT00079391 ↗

Enrolled (actual)

Serious AEs

51.0%

Results posted

May 2012

Primary outcome: Primary: The Proportion of Patients Who Develop Full Donor T Cell Chimerism at Day 30 — 44.9 percentage of participants

Study Design & Population

Study type: Interventional
Phase: Phase 2
Interventions: allogeneic hematopoietic stem cell transplantation (Device)
Age: Pediatric, Adult, Older Adult · 2+ yrs
Sex: All
Sponsor: National Heart, Lung, and Blood Institute (NHLBI)
Primary completion: Dec 2008

Outcome Measures

Outcome	Result	p-value
PRIMARY The Proportion of Patients Who Develop Full Donor T Cell Chimerism at Day 30	44.9	—
SECONDARY Overall Survival	47.9	—
SECONDARY Non Relapse Mortality.	21.1	—
SECONDARY Cumulative Incidence of Relapse	39.8	—
SECONDARY Acute Graft Versus Host Disease (Before Day 60 T Cell Add Back)	20	—
SECONDARY Acute GVHD Overall	39	—

Summary

This study will evaluate the safety and effectiveness of stem cell transplantation in which the donor's T cells (a type of lymphocyte, or white blood cell) are removed and then added back. Certain patients with bone marrow malignancies undergo transplantation of donated stem cells to generate new and normally functioning bone marrow. However, T-cells from the donor may see the patient's cells as foreign and mount an immune response to reject them, causing what is called "graft-versus-host-disease" (GVHD). Therefore, in this protocol, T-cells are removed from the donor cells to prevent this complication. However, because T-cells are important in fighting viral infections as well as any remaining malignant cells (called graft-versus-leukemia effect), the donor T-cells are given to the patient (added back) at a later time after the transplant when they can provide needed immunity with less risk of causing GVHD. Patients between 10 and 55 years of age with acute or chronic leukemia, myelodysplastic syndrome, or myeloproliferative syndrome may be eligible for this study. Prospective participants and their donors are screened with a medical history and physical examination, blood tests (including a test to match for genetic compatibility), breathing tests, chest and sinus x-rays, and tests of heart function. They also undergo a bone marrow biopsy and aspiration. For this procedure, done under local anesthetic, about a tablespoon of bone marrow is withdrawn through a needle inserted into the hipbone. They undergo apheresis to collect lymphocytes for research studies. This procedure involves collecting blood through a needle in the arm, similar to donating a unit of blood. The lymphocytes are then separated and removed by a cell separator machine, and the rest of the blood is returned through a needle in the other arm. Before treatment begins, patients have a central intravenous line (flexible plastic tube) placed in a vein in the chest. This line remains in place during the stem cell transplant and recovery period for drawing and transfusing blood, giving medications, and infusing the donated cells. Preparation for the transfusion includes high-dose radiation and chemotherapy. Patients undergo total body irradiation in 8 doses given in two 30-minute sessions a day for 4 days. Eight days before the transplant, they begin taking fludarabine, and 3 days before the procedure they start cyclophosphamide.

Eligibility Criteria

INCLUSION CRITERIA

RECIPIENT:

1. Ages 10-55 years inclusive (but less than 56)
2. Chronic myelogenous leukemia (CML) in chronic phase
3. Acute lymphoblastic leukemia (ALL) categories
Adults in first remission with high-risk features
All second or subsequent remissions, primary induction failure, partially responding or untreated relapse
4. Acute myelogenous leukemia (AML)
AML in first remission Except AML with good risk karyotypes
All AML in second or subsequent remission, primary induction failure and resistant relapse
5. Myelodysplastic syndromes categories
refractory anemia with transfusion dependence
refractory anemia with excess of blasts
transformation to acute leukemia, chronic myelomonocytic leukemia
6. Myeloproliferative disorders in transformation to acute leukemia
7. Chronic lymphocytic leukemia refractory to fludarabine treatment and with bulky progressive disease or with thrombocytopenia (less than or equal to 100,000 /micro L) or anemia (less than or equal to 10g/dl) not due to recent chemotherapy
8. Non-Hodgkin's lymphoma including Mantle cell lymphoma relapsing or refractory to current chemotherapy and monoclonal antibody treatment and unsuitable for autologous stem cell transplantation
9. No major organ dysfunction precluding transplantation
10. Diffusion capacity of lung for carbon monoxide (DLCO) greater than or equal to 60% predicted
11. Left ventricular ejection fraction: greater than or equal to 40%
12. Eastern Cooperative Oncology Group(ECOG) performance status of 0 or 1
13. Able to give informed consent
14. Negative pregnancy test for women of childbearing age

INCLUSION CRITERIA

DONOR

1. Human leukocyte antigen (HLA) 6/6 identical family donor
2. Weight greater than or equal to 18 kg
3. Age greater than or equal to 2 or less than or equal to 80 years old
4. Fit to receive granulocyte colony -stimulating factor(G-CSF) and give peripheral blood stem cells (normal blood count, normotensive, no history of stroke)

EXCLUSION CRITERIA

RECIPIENT

1. Patient pregnant
2. Age less than 10 years and 56 years or more
3. Patients with CML in chronic phase who are 41 years or over in whom imatinib mesylate (STI-571)is the treatment of choice
4. ECOG performance status of 2 or more
5. Severe psychiatric illness
6. Major anticipated illness or organ failure incompatible with survival from BMT
7. DLCO less than 60% predicted
8. Left ventricular ejection fraction: less than 40%
9. Serum creatinine greater than 3mg/dl
10. Serum bilirubin greater than 4 mg/dl
11. HIV positive 12. Debilitation or age making the risk of intensive myeloablative therapy unacceptable

EXCLUSION CRITERIA

DONOR

1. Pregnant or lactating
2. Donor unfit to receive G-CSF and undergo apheresis
3. HIV positive
4. Weight less than 18 kg
5. Age less than 2 or greater than 80 years
6. Severe psychiatric illness

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT00079391). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.