Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Lymphoma

Leukemia

Hematologic Neoplasms

Primary Myelofibrosis

Hematologic Diseases

Lymphosarcoma

Antineoplastic Agents

Antirheumatic Agents

All Drugs and Chemicals

Anti-Infective Agents

Dermatologic Agents

Central Nervous System Depressants

Other Dietary Supplements

Cyclophosphamide

Fludarabine

Fludarabine phosphate

Cyclosporine

Cyclosporins

Lenograstim

Mycophenolic Acid

Tacrolimus

Benzocaine

Mesna

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Calcineurin Inhibitors

Enzyme Inhibitors

Tannic Acid

Day -6, -5 Fludarabine 30 mg/M2 IV over 30-60 minutes Cyclophosphamide 14.5 mg/kg IV over 1-2 hours\*, Mesna 14.5 mg/kg IV in 4 divided doses

Day -4 through -2 Fludarabine 30 mg/M2 IV over 30-60 minutes

Day -1 Total Body Irradiation 200 cGy, donor apheresis

Day 0 T cell replete PBSC

Days 3, 4 Cyclophosphamide 50 mg/kg IV Mesna 50 mg/kg IV in 4 divided doses

Day 5 Begin tacrolimus ,mycophenolate, and G-CSF

Fludarabine 30 mg/m2/day will be administered over 30-60 minutes intravenous infusion on Days -6 through -2. Fludarabine will be dosed according to the recipient's Adjusted Ideal Body Weight (AIBW) unless AIBW is less than Ideal Body Weight (IBW).

For decreased creatinine clearance (\< 61 mL/min) determined by the Cockcroft Formula:

Cockcroft-Gault CrCl = (140-age) \* (Wt in kg) \* (0.85 if female) / (72 \* Cr)

Fludarabine dosage should be reduced per standard of care.

Pre-transplant

Cy 14.5 mg/kg/day will be administered as a 1-2 hour intravenous infusion with a high volume fluid flush on Days -6 and -5. Cy will be dosed according to the recipient's actual body weight unless the patient weighs more than 125% of IBW, in which case the drug will be dosed according to the adjusted IBW

Post-transplant

Hydration prior to cyclophosphamide may be given according to Standard Practice Guidelines.

Cyclophosphamide \[50mg/kg\] will be given on Day 3 post-transplant (between 60 and 72 hours after marrow infusion) and on Day 4 post-transplant (approximately 24 hours after Day 3 cyclophosphamide). Cy will be dosed according to the recipient's actual body weight unless the patient weighs more than 125% of IBW, in which case the drug will be dosed according to the adjusted IBW. Cyclophosphamide will be given as an IV infusion over 1-2 hours.

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Pre-transplant

Mesna should be given in divided doses IV 30 min pre- and at 3, 6, and 8 hours post-cyclophosphamide. Mesna dose will be based on the cyclophosphamide dose being given. The total daily dose of mesna is equal to 100% of the total daily dose of cyclophosphamide.

Post-transplant

Mesna should be given in divided doses IV 30 min pre- and at 3, 6, and 8 hours post-cyclophosphamide. Mesna dose will be based on the cyclophosphamide dose being given. The total daily dose of mesna is equal to 100% of the total daily dose of cyclophosphamide.

200 cGy will be administered in a single fraction on Day -1 via linear accelerator.

Total Body Irradiation

Donors who consent to PBSC donation will receive 5 daily doses of G-CSF, 10 μg/kg/day by subcutaneous injection commencing on day -5. PBSC's will be collected in the afternoon of day -1, stored at 4C overnight, and infused as soon as possible on day 0. If the collection on day -1 contains less than 5.0 X 106 CD34+ cells per kg recipient weight, a second collection will be performed the following morning and infused on day 0. Quantitation of CD34 and CD3 cells will be performed by the Cellular Therapy Lab. For all patients, the target number of CD34 cells to be infused should be 5-6 X 106 cells per kg recipient weight. PBSC in excess of 6.0 x 106 CD34 cells/kg recipient weight may be cryopreserved.

Hematopoietic stem cell infusion

Tacrolimus will be given at a dose of .03 mg/kg IV over 24 hours. Tacrolimus will be changed to a PO dosing schedule once a therapeutic level is achieved and the patient is tolerating PO. Whole bloodblood levels of tacrolimus will be measured around Day 7 and then should be checked at least weekly thereafter and the dose adjusted accordingly to maintain a level of 5-10 ng/mL. Tacrolimus will be discontinued after the last dose around Day 180, or may be continued if active GVHD is present. Cyclosporine (target concentration 200-400 ng/ml) may be substituted for tacrolimus if the patient is intolerant of tacrolimus.

Either the sodium salt of mycophenolate or mycophenolate mofetil (MMF) may be used as prophylaxis of GvHD and will be dosed by actual bodyweight. Only MMF is available as IV formulation. Sodium mycophenolate will be given at a dose of 10mg/kg PO TID rounded to the nearest number of 180mg tablets. MMF will be given at a dose of 15 mg/kg PO TID. The maximum total daily dose should not exceed 2160 mg (sodium salt) or 3 grams (mofetil). Mycophenolate prophylaxis will be discontinued after the last dose on Day 35, or may be continued if active GVHD is present.

Mycophenolate

G-CSF will be given beginning on Day 5 at a dose of 5 mcg/kg/day (rounding to the nearest vial dose is allowed), until the absolute neutrophil count (ANC) is \> 1,000/mm3 for three consecutive days.

G-CSF

Rafic J Farah, MD

The purpose of this study is to determine whether stem cells collected from a donor's blood stream will be as safe and effective as using bone marrow collected from a donor's pelvic bone.

This is a pilot study to assess the safety and potential efficacy of haploidentical peripheral blood stem cell transplantation using a nonmyeloablative preparative regimen and post-transplant cyclophosphamide. The overall objective of this study is to collect the efficacy and safety data to provide the basis to decide whether a larger study of clinical efficacy is warranted in this setting.

Nonmyeloablative Hematopoietic Cell Transplantation (HCT) for Patients With Hematologic Malignancies Using Related, HLA-Haploidentical Donors: A Pilot Trial of Peripheral Blood Stem Cells (PBSC) as the Donor Source

The cumulative incidence of grades III/IV acute GvHD at day +84 will be assessed. The first day of acute GvHD onset will be used to calculate a cumulative incidence curve by certain grade. An overall cumulative incidence curve will be computed along with a 90% CI with graft failure, relapse/progression, and death as competing risks.

The cumulative incidence of chronic GvHD at one year will be assessed. An overall cumulative incidence curve will be computed along with a 90% CI with graft failure, relapse/progression, and death as competing risks.

The cumulative incidence of NRM at 1 year will be assessed. An overall cumulative incidence curve will be computed along with a 90% CI with relapse/progression as competing risk.

The cumulative incidence of relapse at 1 year will be assessed. An overall cumulative incidence curve will be computed along with a 90% CI with NRM as competing risk.

Achievement of an ANC ≥ 500/mm3 for three consecutive measurements on different days. The first of the three days will be designated the day of neutrophil recovery.

Primary graft failure \< 5% donor CD3 chimerism

Initial recovery followed by neutropenia with \< 5% donor chimerism.

The first day of a sustained platelet count \>20,000/mm3 with no platelet transfusions in the preceding seven days.

Donor chimerism \>= 50% on day \>= 84 after transplantation. Donor engraftment also should be tested on day +28.

Progression-free survival is the minimum time interval to relapse/recurrence, to death or to last follow-up.

Infections will be reported by anatomic site, date of onset, organism and resolution, if any.

Rafic Farah, MD

Assistant Professor of Medicine

Pheochromocytoma

Neuroblastoma

Neuroectodermal Tumors, Primitive, Peripheral

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Neuroepithelial

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Paraganglioma

Neuroendocrine Tumors

Neuroepithelioma

Paragangliomas 1

Neuroendocrine Tumor

Pharmaceutical Solutions

Micronutrients

Iodine

3-Iodobenzylguanidine

Radiopharmaceuticals

Therapeutic 131 I-Metaiodobenzylguanidine (131I-MIBG) will be infused intravenously, intravenous fluids will be administered to help maintain urine flow and isotope excretion. Potassium iodide solution will be administered to protect thyroid function. G-CSF will be used if necessary for neutrophil recovery. Hematopoietic stem cell infusion if meets the criteria.

Minimum dose of 10 mCi/kg and up to 18 mCi/kg maximum will be diluted in 25 ml of normal saline, and will be infused intravenously over 90-120 minutes.

131 I-Metaiodobenzylguanidine (131I-MIBG)

For the therapeutic MIBG administration, potassium iodide solution will be administered in a loading dose of 6mg/kg orally at least 8 hours prior to the MIBG injection, and then will be given at 1mg/kg/dose every 4 hours on days 0-6, then 1 mg/kg/day through day 45 post injection. The minimum dose of potassium iodide to be given is one drop, which equals 50 mg.

Potassium iodide solution

It is recommended that patients with ANC less than 750 after MIBG infusion begin G-CSF 5 mcg/kg/day subcutaneously (or receive equivalent single dose of Neulasta every 14 days while neutropenic) until neutrophil recovery (generally \>5000).

The majority of patients on this protocol will have autologous PBSCs available. Allogeneic stem cells may be utilized in patients who has received a prior allogeneic transplant. The minimum quantity for peripheral blood stem cells is 1.5 x 106 CD34+ cells/kg (optimum \> 2 x 106 CD34+ cells/kg). The minimum dose for bone marrow is 1.0 x 108 mononuclear cells/kg (optimum \>2.0 x 108 mononuclear cells/kg). Infusion will be performed according to institutional guidelines.

hematopoietic stem cell infusion

Emily Greengard, MD

This is a best available therapy/compassionate use single institution study designed to determine the palliative benefit and toxicity of 131I-MIBG in patients with progressive neuroblastoma and metastatic pheochromocytoma who are not eligible for therapies of higher priority. Patients may receive a range of doses depending on stem cell availability and tumor involvement of bone marrow. Response rate, toxicity, and time to progression and death will be evaluated.

Primary Objective is to provide access to therapy with 131I-MIBG for patients with relapsed/refractory neuroblastoma or metastatic pheochromocytoma.

Secondary Objective is to assess disease response to 131I-MIBG therapy for patients with relapsed/refractory neuroblastoma or metastatic pheochromocytoma.

Tertiary Objectives are to 1) gain more information about the toxicities of 131I-MIBG therapy; 2) assess improvement of symptoms, including pain and fatigue, for patients with relapsed/refractory neuroblastoma or metastatic pheochromocytoma who are receiving 131I-MIBG therapy.

* The therapeutic dose of 131I-MIBG will be based on the following:

  1. Minimum dose of 10 mCi/kg for patients without a stem cell source whose renal function is above the upper limit of normal but still meets eligibility criteria.
  2. Dose of 12 mCi/kg for patients without a stem cell source with normal renal function and meets other eligibility criteria.
  3. Dose of \> 12 mCi/kg to 18 mCi/kg maximum at investigator's discretion for patients meeting eligibility criteria with stem cells available.
* A urinary catheter and intravenous fluids will be used for bladder protection, and potassium iodide solution for thyroid Protection.
* G-CSF is recommended for patients with ANC less than 750 after MIBG infusion.
* hematopoietic stem cell infusion is recommended for patients with grade 4 hematologic toxicity following 131I-MIBG therapy that continues to have an ANC \<200 on G-CSF without signs of recovery for \>2 weeks and any patient requiring platelet transfusion more than two times weekly for 4 consecutive weeks.
* Follow-up will be done until disease progression, death or other therapies are initiated.

MIBG for Refractory Neuroblastoma and Pheochromocytoma

131I-Metaiodobenzylguanidine (131I-MIBG) Therapy for Refractory Neuroblastoma and Pheochromocytoma

The number of patients with relapsed/refractory neuroblastoma or metastatic pheochromocytoma who receive access to 131 I-MIBG.

Disease response to 131 I-MIBG therapy in patients with relapsed/refractory neuroblastoma or metastatic pheochromocytoma. Disease response will be measured by Curie Score for patients with MIBG avid disease only or by both Currie Score and RECIST criteria for patients who have measureable disease in addition to MIBG avid disease. Disease response will be assessed at day 56 (+/- 14 days) and then every 3 months until 1-year post treatment, then every 6 months until progression, death or other therapy.

Evaluation of hematologic toxicities of 131I MIBG therapy. CBC with differential and platelet count will be obtained prior to study enrollment, on day 0 and then twice weekly until ANC\>500/mm3 and platelet count \>20,000 x 3 days without transfusion. Once that is achieved CBC will be then obtained on day 56 and then every 3 months until 1 year post treatment, then every 6 months until progression, death or other therapy. In addition, we will be looking at the percent of patient that require infusion of stem cell product for cytopenias.

ALT, AST, bilirubin will be obtained prior to study enrollment and then weekly until day 42, again on day 56 and then every 3 months until 1 year post treatment, then every 6 months until progression, death or other therapy

T4 and TSH will be obtained prior to study enrollment and again on day 56 and then every 3 months until 1 year post treatment, then every 6 months until progression, death or other therapy.

Assessment of pain will occur on day 0 of therapy, on the day of discharge and then weekly until day 42 and then again on day 56. The PedsQL Pediatric Pain Questionnaire will be used for assessment of pain in all patients. These questionnaires include both patient report and parent report, when appropriate.

Assessment of fatigue will occur on day 0 of therapy, on the day of discharge and then weekly until day 42 and then again on day 56. The PedsQL Multidimensional Fatigue Scale will be used for assessment of fatigue in all patients. These scales include both patient report and parent report, when appropriate.

Masonic Cancer Center, University of Minnesota

Heart and Blood Diseases

Symptoms and General Pathology

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Multiple Myeloma

Neoplasms, Plasma Cell

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Lymphoproliferative Disorders

Myeloproliferative Disorders

Paraproteinemias

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Blood Protein Disorders

Hemorrhagic Disorders

Immunoproliferative Disorders

Lymphatic Diseases

Bone Marrow Diseases

Chronic Disease

Disease Attributes

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Chronic Graft Versus Host Disease

Chronic Myeloid Leukemia

Acute Graft Versus Host Disease

Chronic Myeloproliferative Disorders

Busulfan

Alemtuzumab

Antineoplastic Agents, Immunological

Recipients of HLA identical sibling stem cell transplants

Recipients of unrelated matched or single antigen mismatched donor stem cell transplant or single antigen mismatched family donor stem cell transplants

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

Campath

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.

FK-506

Rammurti T Kamble, MD

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:

1. Busulfan 3.2 mg/kg/day IV daily for 2 days, infused over 3 hours, on Day -5 and Day -4
2. Fludarabine 30mg/m2/day IV daily for 4 days on Day -5 to D -2
3. Campath 10 mg/day IV daily for 3 days on days -6 to D-4.

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.

Reduced Intensity Preparative Regimen Followed by Stem Cell Transplant (FAB)

Reduced-Intensity Preparative Regiment With Fludarabine, Busulfan, And Alemtuzumab (Campath 1H) Followed By Allogeneic Hematopoietic Stem Cell Transplant For Malignant And Non-Malignant Hematological Diseases

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.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Nonmyeloablative Hematopoietic Cell Transplantation (HCT) for Patients With Hematologic Malignancies Using Related, HLA-Haploidentical Donors: A Pilot Trial of Peripheral Blood Stem Cells (PBSC) as the Donor Source	NCT02167958	Leukemia MDS Myelofibrosis Lymphoma	Fludarabine Cyclophosphamid... Mesna Total Body Irra... Hematopoietic s... Tacrolimus Mycophenolate G-CSF	18 Years - 70 Years	University of Pittsburgh
MIBG for Refractory Neuroblastoma and Pheochromocytoma	NCT01850888	Relapsed Neurob... Metastatic Pheo...	131 I-Metaiodob... Potassium iodid... G-CSF hematopoietic s...	1 Year -	Masonic Cancer Center, University of Minnesota
Reduced Intensity Preparative Regimen Followed by Stem Cell Transplant (FAB)	NCT00579111	Myelodysplastic... Acute Myelogeno... Acute Lymphobla... Chronic Myeloge... Multiple Myelom... Plasma Cell Dys... Lymphoprolifera... Hematologic Dis...	Campath Busulfan Fludarabine Hematopoietic s... FK-506	- 70 Years	Baylor College of Medicine

Spots Global Cancer Trial Database for hematopoietic stem cell infusion