Neoplasms

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Syndrome

Lymphoma

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Neoplasms by Histologic Type

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Antineoplastic Agents

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All Drugs and Chemicals

Cyclophosphamide

Fludarabine

Fludarabine phosphate

MEDI-507 0.1 mg/kg on transplant day-8, 0.6 mg/kg on days-7 and -6

MEDI-507

Cyclophosphamide 60 mg/kg on transplant days -7 and -6; Fludarabine 25 mg/m2 days -5,-4,-3,-2,-1; MEDI-507 0.1 mg/kg on day -8, 0.6 mg/kg on days -7,-6

Non-myeloablative Ex-Vivo T-cell Depleted PBSC Transplant

Thomas Spitzer, M.D.

The purpose of this study is to determine if recipients of non-myeloablative ex-vivo T-cell depleted peripheral blood (PBSC) stem cell transplantation using a mismatched related donor will have less severe graft versus host disease (GVHD), transplant related mortality, and less graft failure compared to alternative haploidentical stem cell transplantation.

One major obstacle to further advancement in the role of bone marrow transplant (BMT) in hematological malignancies is graft-versus-host-disease (GVHD), which can best be prevented by removing T-cells from the donor stem cell product. However, previous experience with T-cell depletion has been associated with an increased rate of engraftment failure and leukemic relapse. Another obstacle is that a large fraction of leukemia and lymphomas afflict older patients who are more prone to GVHD and have co-morbid conditions that prevent them from being a candidate for BMT.

This trial uses a non-myeloablative conditioning regimen with cyclophosphamide, MEDI-507, fludarabine, and thymic irradiation followed by a T-cell depleted PBSC infusion. Cyclosporine is used for GVHD prophylaxis, and tapered beginning on day 35. Data from our mouse model and previous clinical trials have demonstrated that this approach can induce mixed chimerism without GVHD, with the potential for conversion of mixed chimerism to full donor hematopoiesis following donor leukocyte infusions.

Non-Myeloablative HLA-Mismatched Ex-Vivo T-cell Depleted Stem Cell Transplantation for Hematologic Malignancies

Dana-Farber Cancer Institute

Massachusetts General Hospital

Director Cellular Therapy and Transplantation Laboratory

Lymphatic Diseases

Anti-Infective Agents

Channel Blockers

Anticonvulsants

Mycophenolic Acid

Tacrolimus

Busulfan

Phenytoin

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

* All participants except those with acute lymphoblastic leukemia and lymphoblastic lymphoma: Busulfan will be administered 1 mg/kg oral (or 0.8 mg/kg IV) four times per day for four days, followed by cyclophosphamide 50 mg/kg once per day for two days.
* Participants with acute lymphocytic leukemia or lymphoblastic lymphoma: Cyclophosphamide will be administered 50 mg/kg once per day for two days, followed by total body irradiation at 300 cGy per day for four days.

Participant will receive Busulfan injections, 4 times a day for 4 days with dilantin prophylaxis (in patients 10 years of age or older). Busulfan levels in the blood will be measured and dose adjusted, if needed.

Patient will receive Cy by IV once a day for 2 days.

Patients will receive TBI once a day for 4 days.

Total body irradiation

Heather Symons, M.D.

The purpose of this study is to see if giving high dose chemotherapy and total body irradiation before and repeating high dose chemotherapy after a bone marrow transplant could reduce the incidence of graft rejection and disease for patients with blood cancers

Allogeneic blood or marrow transplantation (alloBMT), following either marrow-ablative or nonmyeloablative conditioning, is a potentially curative treatment for a variety of hematologic malignancies and non-malignant hematologic disorders. Of all the potential sources of allografts, transplantation of stem cells from a human leukocyte antigen (HLA)-matched sibling has generally produced the best overall outcomes, i.e. overall and progression-free survival. Unfortunately, only about a third of candidates for alloBMT have HLA-matched siblings.

For patients who lack HLA-matched siblings, there are three alternative sources of stem cells for alloBMT: 1) volunteer unrelated donors; 2) umbilical cord blood; and 3) partially HLA-mismatched, or haploidentical, related donors. Since any patient shares exactly one HLA haplotype with each biological parent or child and half of siblings, an eligible haploidentical donor can be identified rapidly in nearly all cases. However, haploidentical BMT has been associated with significant risks of graft rejection and severe GVHD, which are manifestations of excessive alloreactivity by host and donor T cells, respectively.

The risk of severe GVHD may be reduced in intensively conditioned recipients of grafts that have been rigorously depleted of mature T cells or selectively depleted of alloreactive T cells, but the risks of serious infection and death from prolonged immune compromise in these patients remains high. Cyclophosphamide(Cy) is a highly immunosuppressive antineoplastic agent that has an established role in conditioning for alloBMT.

Typically, the drug is administered prior to transplantation to prevent graft rejection by suppressing the host immune system. However, pre-transplantation conditioning with Cy increases the risk of GVHD following allogeneic T cell infusion in mouse models. In contrast, administration of a properly timed, high dose of Cy after BMT inhibits both graft rejection and GVHD.

Safety Study of Bone Marrow Transplant Using Mismatched Tissue Followed by Chemotherapy

A Phase II Trial of Myeloablative Conditioning and Transplantation of Partially HLA-mismatched Bone Marrow for Patients With Hematologic Malignancies

Percentage of participants who achieved donor chimerism \>=95%.

Number of participants deceased for reasons other than disease relapse or progression.

Percentage of participants who experience grade II-IV or III-IV acute graft-versus-host-disease (GVHD) by Przepiorka criteria. The stages are defined as follows:

* Stage II: Rash on \>50% of skin, bilirubin 2-3 mg/dL, or diarrhea 500-1000 mL/day
* Stage III: Bilirubin 3-15 mg/dL or diarrhea \>1000 mL/day
* Stage IV: Generalized erythroderma with bullae or bilirubin \>15 mg/dL This outcome was estimated using proportional subdistribution hazard regression model for competing risks (Fine and Gray 1999)

Percentage of participants who experience chronic GVHD. Chronic GVHD is graded using NIH consensus criteria and Seattle criteria. This outcome was estimated using proportional subdistribution hazard regression model for competing risks (Fine and Gray 1999)

Percentage of participants alive (overall survival) and alive without disease relapse, progression, or diagnosis of myeloid malignancy (event-free survival). Estimated using Kaplan-Meier method.

Percentage of participants who experienced disease progression or relapse. This outcome was estimated using proportional subdistribution hazard regression model for competing risks (Fine and Gray 1999)

Otsuka Pharmaceutical Co., Ltd.

National Center for Research Resources (NCRR)

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Only the following adverse events were collected per protocol: non-relapse mortality in the first 100 days after BMT; graft failure; and all unexpected events considered significant by the principal investigator. Adverse events were assessed weekly through Day 60 and at Days 180, 365, and 730.

Myeloablative Haploidentical BMT

Age, Categorical

Age, Continuous

Sex: Female, Male

Race and Ethnicity were not collected from any participant.

Race and Ethnicity Not Collected

United States

Region of Enrollment

The entire set of participants was analyzed as one group, and the analysis was planned this way from the beginning of the study.

Heather Symons, MD

8 participants were not evaluable for this outcome because they died prior to Day 60.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Non-Myeloablative HLA-Mismatched Ex-Vivo T-cell Depleted Stem Cell Transplantation for Hematologic Malignancies	NCT00113646	Lymphoma Leukemia Multiple Myelom... Myelodysplastic...	MEDI-507 Non-myeloablati...	- 65 Years	Massachusetts General Hospital
Safety Study of Bone Marrow Transplant Using Mismatched Tissue Followed by Chemotherapy	NCT00796562	MDS Leukemias Lymphomas	Busulfan Cyclophosphamid... Total body irra...	6 Months - 65 Years	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Spots Global Cancer Trial Database for mismatched

Every month we try and update this database with for mismatched cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for mismatched

Every month we try and update this database with for mismatched cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for mismatched cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.