A Phase 1/2 interventional study of Campath and Busulfan in Myelodysplastic and Myeloproliferative Disorders, Acute Myelogenous Leukemia and Acute Lymphoblastic Leukemia, sponsored by Baylor College of Medicine. Terminated at 2 sites in United States. Open to participants aged Up to 70 Years. Per ClinicalTrials.gov, last updated 2016-05-04.
Sponsored by Baylor College of Medicine · Phase 1/2, Interventional, and Treatment
Blood disorders such as leukemia or lymphoma or hemoglobinopathies can benefit from receiving an allogeneic (meaning that the cells are from a donor) stem cell transplant. Stem cells are created in the bone marrow. They grow into different types of blood cells that the body needs, including red blood cells, white blood cells, and platelets. In a transplant, the body's stem cells would be killed and then replaced by stem cells from the donor. Usually, patients are given very high doses of chemotherapy (drugs which kill cancer cells) prior to receiving a stem cell transplant. However, patients that are older, have received several prior treatments, or have other organ diseases are at a high risk of getting life-threatening treatment-related side effects from high doses of chemotherapy. Over the past several years, some doctors have begun to use lower doses of chemotherapy for preparing patients for a stem cell transplant.
A condition that can occur after a stem cell transplant from a donor is Graft Versus Host Disease (GVHD). It is a rare but serious disorder that can strike persons whose immune system is suppressed and have received either a blood transfusion or a bone marrow transplant. Symptoms may include skin rash, intestinal problems similar to inflammation of the bowel and liver dysfunction.
This research study uses a combination of lower-dose chemotherapy agents that is slightly different from those that have been used before.
The medicines that will be used in this study are Fludarabine, Busulfan, both chemotherapy medicines, and Campath. Campath is a monoclonal antibody (a type of substance produced in the laboratory that binds to cancer cells). It helps the immune system see the cancer cell as something that needs to be destroyed.
This research study will help us learn if using Fludarabine, Busulfan and Campath prior to an allogeneic stem cell transplant can provide treatment for blood disorders while decreasing the incidence of side effects.
Allogeneic stem cell transplantation with high-dose chemotherapy affords a better chance of cure of malignant and non-malignant hematological diseases compared to autologous transplantation, because of the lack of stem cell contamination and the immune mediated graft vs. leukemia effect. Unfortunately, high-dose chemotherapy and allogeneic stem cell transplantation has a substantial treatment related mortality, that is particularly high in older patients (greater than 50 yrs of age), or in those with co-morbidities such as congestive heart disease and pulmonary disease. Patients who have pre-existing infections or who have had multiple relapses with prior chemotherapy are also at high risk. In all these groups, treatment related mortality may exceed 50%, making them ineligible for high-dose chemotherapy and allogeneic stem cell transplantation.
Recently interest has increased in using less toxic chemotherapy protocols that are termed submyeloablative. The intent is to allow partial engraftment of a donor immune and hemopoietic systems with subsequent progressive replacement of the host's own hemopoiesis and immunity. As the donor immune system becomes established, patients may develop full donor chimerism, without passing through the period of prolonged aplasia associated with conventional conditioning regimens, and with less of the associated toxicity. Preliminary results in high-risk patients have shown treatment related mortality (TRM) of 15-20%, versus 50% expected, with an overall survival rate of 70-80% at 1-2 years post transplant.
As might be anticipated, the major problem with sub-ablative conditioning is that the graft failure rate is increased, with published figures of 5-30% versus 1-5% predicted in fully ablated patients. The incorporation of lymphodepleting antibodies in the preliminary conditioning regimen may allow these rejection rates to be diminished. Moreover, a highly efficient lymphodepleting MAb or MAb combination might be successfully substituted in part or in whole for cytotoxic and immunosuppressive drugs, further increasing the safety and efficacy of the subablative approach to stem cell transplantation. Our own data using the crude polyclonal mixture of antibodies in ATG as a component of pre-transplant conditioning revealed an improvement in engraftment during matched unrelated donor transplantation.The lymphodepleting monoclonal antibody Campath IH has many of the properties desired for this application, and we propose to incorporate it in our conditioning regimen. Since CAMPATH1H persists after infusion, we would expect it to have additional anti-GvHD effector function, further reducing treatment related mortality (TRM).
The following preparative regimen will be delivered to all patients:
Because CAMPATH-1H infusions will provide a persisting level of antibody over the transplant period, it will contribute to anti-GvHD activity. Additional Graft vs. host disease prophylaxis will consist of FK506 administered from Day-2.
The stem cells will be infused on day 0.
5,441 studies on the registry are indexed under Leukemia; 636 are open to participants now.
This study's enrollment of 4 is below the median of 38 across 4,247 interventional studies indexed under Leukemia.
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Of its 83 completed or terminated interventional studies of FDA-regulated products, 44 (53%) have results posted.
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Conditions that increase treatment related mortality (need more than one to be eligible):
Available healthy donor without any contraindications for donation
Exclusion Criteria:
Recipients of HLA identical sibling stem cell transplants
Drug: Campath · Drug: Busulfan · Drug: Fludarabine · Procedure: Hematopoietic stem cell infusion · Drug: FK-506
Recipients of unrelated matched or single antigen mismatched donor stem cell transplant or single antigen mismatched family donor stem cell transplants
Drug: Campath · Drug: Busulfan · Drug: Fludarabine · Procedure: Hematopoietic stem cell infusion · Drug: FK-506
10 mg/day IV daily for 3 days on days -6 to D-4. Campath may be omitted from the conditioning regimen for patients with malignant diseases and matched related donor transplants
Also known as: Alemtuzumab
3.2 mg/kg/day IV daily for 2 days, infused over 3 hours, on Day -5 and Day -4
30mg/m2/day IV daily for 4 days on Day -5 to D -2
Peripheral blood stem cells when possible. Bone marrow cells will be used if peripheral blood cells are insufficient or unavailable.
FK-506 at a dose of 0.03 mg/kd/day will be administered via continuous infusion over 24 hours from 4pm on Day -2 until engraftment or when the patient is able to take PO, then 0.03 mg/kg PO every 12 hours.
Also known as: Tacrolimus
Number of Patients With Successful Donor Engraftment
Each patient will be classified as a success or failure. A success will be defined as engraftment of at least 35% of cells 100 days after transplant.
Time frame: 100 days
Number of Patients With Treatment Related Grade III or IV Non-hematological Toxicity
Time frame: 100 days
| Milestone | HLA-identical Sibling Transplant | Unrelated Matched or Single Antigen Mismatched Transplant |
|---|---|---|
| Started | 3 | 1 |
| Completed | 1 | 0 |
| Not completed | 2 | 1 |
Each patient will be classified as a success or failure. A success will be defined as engraftment of at least 35% of cells 100 days after transplant.
| participants | HLA-identical Sibling Transplant | Unrelated Matched or Single Antigen Mismatched Transplant |
|---|---|---|
| Number of Patients With Successful Donor Engraftment | 2 | 1 |
| participants | HLA-identical Sibling Transplant | Unrelated Matched or Single Antigen Mismatched Transplant |
|---|---|---|
| Number of Patients With Treatment Related Grade III or IV Non-hematological Toxicity | 1 | 0 |
Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| HLA-identical Sibling Transplant | — | 2/3 (66.7%) | 0/3 (0%) |
| Unrelated Matched or Single Antigen Mismatched Transplant | — | 0/1 (0%) | 0/1 (0%) |
| Event | HLA-identical Sibling Transplant | Unrelated Matched or Single Antigen Mismatched Transplant |
|---|---|---|
| Blood/Bone Marrow - Other: Engraftment FailureBlood and lymphatic system disorders | 1/3 | 0/1 |
| Infection (documented clinically or microbiologically) with Grade 3 or 4 neutrophils (ANC <1.0 x 10eInfections and infestations | 1/3 | 0/1 |
| Age, Customized(participants) | HLA-identical Sibling Transplant | Unrelated Matched or Single Antigen Mismatched Transplant | Total |
|---|---|---|---|
| Between 50 and 65 years | 3 | 0 | 3 |
| >=65 years | 0 | 1 | 1 |
| Sex: Female, Male(Participants) | HLA-identical Sibling Transplant | Unrelated Matched or Single Antigen Mismatched Transplant | Total |
|---|---|---|---|
| Female | 1 | 0 | 1 |
| Male | 2 | 1 | 3 |
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