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Anti-Infective Agents

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All Drugs and Chemicals

Mycophenolic Acid

Tacrolimus

Immunosuppressive Agents

Immunologic Factors

Calcineurin Inhibitors

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Anti-Bacterial Agents

Antibiotics, Antitubercular

Antitubercular Agents

peripheral blood lymphocyte therapy

mycophenolate mofetil

tacrolimus

allogeneic bone marrow transplantation

radiation therapy

Ephraim J. Fuchs, MD

RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Bone marrow transplantation may be able to replace immune cells that have been destroyed by radiation therapy used to kill tumor cells. Sometimes the transplanted cells can make an immune response against the body's normal tissues. Mycophenolate mofetil and tacrolimus may be an effective treatment for graft-versus-host disease caused by bone marrow transplantation.

PURPOSE: Phase II trial to study the effectiveness of total-body irradiation, tacrolimus, and mycophenolate mofetil plus bone marrow transplantation in treating patients with hematologic cancers.

OBJECTIVES: I. Determine whether sustained engraftment of HLA identical sibling marrow can be achieved in patients treated with total body irradiation before transplant and tacrolimus and mycophenolate mofetil after transplant. II. Document the nonhematologic toxicities of this regimen. III. Characterize immune reconstitution of patients during this treatment regimen. IV. Document the incidence of aplasia and graft-versus-host disease associated with donor leukocyte infusions when administered after this regimen.

OUTLINE: Patients receive total body irradiation in a single fraction on day -1. Tacrolimus is given orally twice per day on days -1 to 50. Mycophenolate mofetil is given orally on day 0 and twice per day on days 1 to 28. Patients receive donor bone marrow infusion on day 0. Patients are evaluated on days 56, 180, 292, and 365. If there is donor engraftment, donor chimerism is less than 80%, there is no active graft-versus-host disease, no disease progression, less than 50% decrease in donor cell chimerism from last measurement, and the patient is not taking immunosuppressive agents, then donor leukocyte infusions are administered on days 70, 194, and 306. Patients are followed annually for 5 years.

PROJECTED ACCRUAL: A total of 20 patients will be accrued for this study.

Total-Body Irradiation, Tacrolimus, and Mycophenolate Mofetil Plus Bone Marrow Transplantation in Treating Patients With Hematologic Cancers

Non-Myeloablative Allogeneic Bone Marrow Transplant for Hematologic Malignancies

National Cancer Institute (NCI)

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Diseases and Abnormalities at or Before Birth

Congenital Abnormalities

Vaccines

Immunomodulating Agents

autologous tumor cell vaccine

Carol A. Huff, MD

RATIONALE: Vaccines made from the patient's cancer cells may help the body build an effective immune response to kill cancer cells. Giving vaccine therapy together with donor lymphocyte infusion after a stem cell transplant from the patient's brother or sister may kill any cancer cells that remain after transplant.

PURPOSE: This clinical trial is studying the side effects, best dose, and how well vaccine therapy with or without donor lymphocyte infusion works in treating patients with acute myeloid leukemia, acute lymphoblastic leukemia, or multiple myeloma undergoing donor stem cell transplant.

OBJECTIVES:

* Determine time to relapse and overall survival of patients with high-risk acute myeloid leukemia, acute lymphoblastic leukemia, or multiple myeloma treated with autologous tumor cell vaccine with or without donor lymphocyte infusion after HLA-matched related sibling nonmyeloablative hematopoietic stem cell transplantation.
* Evaluate the safety and tolerability of this regimen in these patients.
* Determine the maximum tolerated dose of donor lymphocyte infusions in these patients.

OUTLINE: Patients undergo collection of tumor cells for production of the cancer cell vaccine and then undergo HLA-matched related sibling nonmyeloablative hematopoietic stem cell transplantation (HSCT). Patients then receive cancer cell vaccine with or without donor lymphocyte infusion. The donor lymphocytes are obtained from the same relative who donated stem cells for the HSCT.

PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study.

Vaccine Therapy With or Without Donor Lymphocyte Infusion in Treating Patients With Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, or Multiple Myeloma Undergoing Donor Stem Cell Transplant

Posttransplant Immunotherapy With Donor Lymphocyte Infusions and Autologous Tumor Vaccines After HLA-Matched Transplant

Anemia

Anemia, Refractory, with Excess of Blasts

Anemia, Refractory

Childhood Acute Lymphoblastic Leukemia

Myelodysplastic Syndrome With Excess Blasts

Anti-Inflammatory Agents

Antiemetics

Neuroprotective Agents

Gastrointestinal Agents

Fludarabine

Fludarabine phosphate

Prednisolone

Methylprednisolone

Thiotepa

Methylprednisolone Acetate

Methylprednisolone Hemisuccinate

Prednisolone acetate

Prednisolone hemisuccinate

Prednisolone phosphate

Antilymphocyte Serum

Antimetabolites

Glucocorticoids

Hormones

Hormone Antagonists

Protective Agents

Antineoplastic Agents, Alkylating

Alkylating Agents

administration of donor lymphocytes made using costimulatory blockade ex vivo

anti-thymocyte globulin

fludarabine phosphate

methylprednisolone

thiotepa

allogeneic hematopoietic stem cell transplantation

in vitro-treated peripheral blood stem cell transplantation

total-body irradiation

Eva Guinan, MD

RATIONALE: Giving total-body irradiation and chemotherapy, such as thiotepa and fludarabine, before a donor stem cell transplant helps stop the growth of cancer or abnormal cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving methylprednisolone and antithymocyte globulin before transplant and peripheral blood cells that have been treated in the laboratory after transplant may stop this from happening.

PURPOSE: This phase I trial is studying the side effects and best dose of laboratory-treated peripheral blood cell infusion after donor stem cell transplant in treating patients with hematologic cancers or other diseases.

OBJECTIVES:

Primary

* Establish the feasibility of delayed infusion of ex vivo anergized donor peripheral blood mononuclear cells (PBMC) after CD34 (cluster designation 34)-selected megadose haploidentical hematopoietic stem cell transplantation (HSCT) in patients with hematopoietic cancers or other diseases.
* Determine the feasibility of collecting parental allogeneic stimulator cells to induce anergy to the nonshared donor-recipient haplotype in these patients.
* Determine the feasibility of collecting donor PBMC as a source of T cells for ex vivo anergization.
* Determine the number of transplanted individuals who meet the criteria for proceeding to delayed infusion of ex vivo anergized donor PBMC.
* Establish the safety of delayed infusion of ex vivo anergized donor PBMC by establishing the maximum number of donor T cells that can be infused without unacceptable graft-versus-host disease.

Secondary

* Evaluate, in vitro, the induction and specificity of alloantigen hyporesponsiveness in donor PBMC after ex vivo anergization.
* Assess, in vitro, the function of immune cells engrafted in these patients.
* Assess, in vitro, whether alloantigen hyporesponsive donor T cells are present in these patients.
* Develop, preliminarily, in vitro data on the extent of pathogen-specific immunity and its rate of recovery.
* Describe the patterns of opportunistic infections in these patients.

OUTLINE: This is a multicenter, dose-escalation study of ex vivo anergized allogeneic peripheral blood mononuclear cells (PBMC). Patients who are treated on any dose level except dose level 1 are stratified according to age (under 17 \[pediatric\] vs 17 and over \[adult\]).

* Myeloablative conditioning regimen: Patients undergo total-body irradiation twice daily on days -11 to -9. Patients also receive thiotepa IV over 4 hours on days -8 and -7, fludarabine phosphate IV over 30 minutes on days -7 to -3, and anti-thymocyte globulin IV over 8 hours and methylprednisolone IV over 15-30 minutes on days -6 to -3.
* Allogeneic peripheral blood stem cell transplantation (PBSCT): Patients undergo CD34-selected PBSCT on day 0.
* Ex vivo anergized allogeneic PBMC infusion: If cells have engrafted and patients are free of active uncontrolled infection and graft-vs-host disease, patients undergo allogeneic or autologous PBMC infusion on day 35 or 42.

Cohorts of 3-8 patients receive escalating doses of ex vivo anergized allogeneic PBMCs until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 2 of 5 or 3 of 8 patients experience dose-limiting toxicity.

After completion of study, patients are followed periodically for 2 years.

PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study.

Laboratory-Treated Lymphocyte Infusion After Haploidentical Donor Stem Cell Transplant

Delayed Infusion of Ex Vivo Anergized Peripheral Blood Mononuclear Cells Following CD34 Selected Peripheral Blood Stem Cell Transplantation From a Haploidentical Donor for Patients With Acute Leukemia and Myelodysplasia

ability to collect sufficient cells, make anergized product with good viability, without contamination and infuse per study toxicity of the conditioning regimen, the likelihood of engraftment, and the subsequent percentage of individuals who would be eligible to receive aDLI were determined.

rates of graft failure with CD34 selected product, adverse and severe adverse reactions attributable to infusion of anergized donor cells, including fever, hypotension, acute graft vs host disease, organ dysfunction

incidence of viral infection and type of immune reconstitution by phenotype and function of T cells

National Institute of Allergy and Infectious Diseases (NIAID)

Dana-Farber Cancer Institute

Principal Investigator

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Total-Body Irradiation, Tacrolimus, and Mycophenolate Mofetil Plus Bone Marrow Transplantation in Treating Patients With Hematologic Cancers	NCT00003572	Leukemia Lymphoma Multiple Myelom... Myelodysplastic...	peripheral bloo... mycophenolate m... tacrolimus allogeneic bone... radiation thera...	18 Years - 70 Years	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Vaccine Therapy With or Without Donor Lymphocyte Infusion in Treating Patients With Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, or Multiple Myeloma Undergoing Donor Stem Cell Transplant	NCT00469820	Leukemia Multiple Myelom...	autologous tumo... peripheral bloo...	18 Years - 70 Years	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Laboratory-Treated Lymphocyte Infusion After Haploidentical Donor Stem Cell Transplant	NCT00376480	Leukemia Myelodysplastic...	anti-thymocyte ... peripheral bloo... fludarabine pho... methylprednisol... thiotepa allogeneic hema... in vitro-treate... total-body irra...	- 50 Years	Dana-Farber Cancer Institute
Laboratory-Treated Lymphocyte Infusion After Haploidentical Donor Stem Cell Transplant	NCT00376480	Leukemia Myelodysplastic...	anti-thymocyte ... peripheral bloo... fludarabine pho... methylprednisol... thiotepa allogeneic hema... in vitro-treate... total-body irra...	- 50 Years	Dana-Farber Cancer Institute
Total-Body Irradiation, Tacrolimus, and Mycophenolate Mofetil Plus Bone Marrow Transplantation in Treating Patients With Hematologic Cancers	NCT00003572	Leukemia Lymphoma Multiple Myelom... Myelodysplastic...	peripheral bloo... mycophenolate m... tacrolimus allogeneic bone... radiation thera...	18 Years - 70 Years	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

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