Neoplasms

Digestive System Diseases

Gland and Hormone Related Diseases

All Conditions

Symptoms and General Pathology

Nervous System Diseases

Rare Diseases

Pancreatic Neoplasms

Cancer Pain

Pain

Abdominal Pain

Visceral Pain

Gastrointestinal Neoplasms

Digestive System Neoplasms

Endocrine Gland Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Endocrine System Diseases

Nociceptive Pain

Neurologic Manifestations

Pancreatic Cancer

This arm provides active 1Hz repetitive TMS (rTMS) applied to SII

This arm provides sham 1Hz repetitive TMS (rTMS) applied to SII

1Hz repetitive transcranial magnetic stimulation for 10 days 26 minutes each day

Transcranial Magnetic Stimulation

Felipe Fregni, MD, PhD

This is a phase II study that aims to investigate prospectively a new therapy for a cohort of patients with chronic pain attributed to pancreatic cancer. The justification of this study is that the pain is the most important factor for the quality of life of these patients and rTMS has been shown to be significantly associated with pain improvement in patients with abdominal pain due to chronic pancreatitis. This therapeutic trial will be a 10-day, randomized, parallel-group design, double-blind, incomplete cross-over, placebo controlled clinical trial conducted at Beth Israel Deaconess Medical Center. The principal aim of this investigation is the study of pain after a therapeutic intervention. The primary outcome is pain reduction indexed by pain reduction and or analgesic intake reduction. The second aim of the study is to assess the safety this new treatment in patients with pancreatic cancer. The third aim of this study is to investigate whether rTMS treatment is associated with a change in the activity of right secondary somatosensory cortex using magnetic resonance spectroscopy. Because patients with locally advanced or advanced pancreatic cancer often require increasing doses of narcotic pain medications, such as morphine, oxycodone and fentanyl, in order to control their pain, adverse side effects are frequent observed in this population of patients. Therefore rTMS treatment might represent a new therapeutic approach that might be useful not only for pancreatic cancer but also to other types of cancer.

The primary aim of this protocol is to investigate a possible novel treatment for visceral pain in patients with locally advanced or advanced pancreatic cancer. Pain is a major contributor to the poor quality of life in patients with pancreatic cancer. Most patients with locally advanced or advanced pancreatic cancer have abdominal pain that requires treatment with increasing doses of narcotic pain medication. The refractory nature of pancreatic cancer pain to pharmacologic therapy led us to hypothesize that one mechanism leading to pain in these patients is dysfunction of brain cortical regulation of visceral sensation. This notion is supported by the finding that deep electrical stimulation of the brain can produce pain relief in patients with intractable pain due to progressive cancers of various types. In addition, patients with pancreatitis, a non-malignant pancreatic condition causing chronic pain, can continue to experience disabling pain even after total pancreatectomy. These finding suggests that pain symptoms in pancreatic cancer can be sustained by a pancreas-independent, neural-based mechanisms in the brain.

Visceral sensation is processed in the secondary somatosensory area (SII). Therefore, pancreatic cancer pain may be sustained by dysfunction of SII rather than by local effects of the cancer alone. We hypothesize further, that dysfunction of SII is one of hyper-excitability. According to this hypothesis, suppression of SII activity may help control the pain in patients with pancreatic cancer and may provide synergy with pharmacologic treatment.

Temporary inhibition of SII activity can be obtained by a novel, non-invasive procedure called transcranial magnetic stimulation (TMS). TMS can suppress brain excitability beyond the duration of the direct application of TMS if appropriate stimulation parameters are utilized. This hypothesis is supported by a sham controlled, double blind pilot trial of 5 subjects with idiopathic chronic pancreatitis: active rTMS applied to SII resulted in significant pain improvement in three of the subjects while sham did not provide any benefit in any of these patients. Furthermore, recent evidence suggests that stimulation of other brain areas, such as the dorsolateral pre-frontal cortex, can modulate acute, experimentally invoked pain (Graff-Guerrero et al 2005).

We will rigorously test the hypothesis that pain due to pancreatic cancer is sustained by dysfunction of SII characterized by hyperexcitability through two specific aims:

1. The first aim of this study is to examine whether 1Hz repetitive TMS (rTMS) applied to SII for ten days during two consecutive weeks in patients with abdominal pain due to pancreatic cancer has an analgesic effect.

   1. The primary outcome for this aim is the difference in pain score level on the Visual Analogue Scale at Day 11 and at Day 28 compared to the week before rTMS. The null hypothesis is that there is no difference in pain score between pre and post-treatment.
   2. The secondary outcome for this aim is to assess the difference in the use of narcotics for pain control on Day 11 and Day 28 compared to Day 1. The null hypothesis is that there is no difference in narcotic use (in IV morphine equivalency units) between pre and post-treatment.
2. The second aim of the study is to assess the safety of rTMS in patients with pancreatic cancer.
3. The third aim of this study is to investigate whether rTMS treatment is associated with a change in the activity of right SII using magnetic resonance spectroscopy. Therefore we will compare the levels of these substances between the two different time points (baseline and post-treatment) and between left and right SII. We expect a decrease in the excitatory neurotransmitters levels (Glutamine - Glx) in the stimulated area as a result of the inhibitory rTMS.

SAFETY In a pilot study of chronic pancreatitis patients, no subject experienced adverse effects from a single session of rTMS. Subjects in an ongoing study of a 10-day course or rTMS in chronic pancreatitis patients also have not experienced adverse events (10 patients thus far). Fifteen-day courses of rTMS have been used for the treatment of various neuropsychiatric diseases without any complications if safety guidelines are carefully followed. We will adhere to the current safety recommendations for rTMS endorsed by the International Society for Transcranial Stimulation and the International Federation for Clinical Neurophysiology. Therefore, we hypothesize that the proposed rTMS protocol will be safe for our patient population.

TMS for the Treatment of Pancreatic Cancer Pain

The Effect of a 10-day Course of Transcranial Magnetic Stimulation on Abdominal Pain in Patients With Locally Advanced and Advanced Pancreatic Cancer, a Randomized Phase II Study.

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Beth Israel Deaconess Medical Center

Principal Investigator

Heart and Blood Diseases

Blood and Lymph Conditions

Immune System Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Syndrome

Lymphoma

Leukemia

Graft vs Host Disease

Hodgkin Disease

Preleukemia

Myelodysplastic Syndromes

Precancerous Conditions

Hematologic Diseases

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hemorrhagic Disorders

Bone Marrow Diseases

Lymphosarcoma

Homologous Wasting Disease

Hodgkin Lymphoma

Acute Graft Versus Host Disease

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Antirheumatic Agents

Dermatologic Agents

Reproductive Control Agents

Etoposide

Cytarabine

Cyclophosphamide

Fludarabine

Fludarabine phosphate

Doxorubicin

Liposomal doxorubicin

Methotrexate

Rituximab

Vincristine

Cyclosporine

Cyclosporins

Lenograstim

Tacrolimus

Sirolimus

Etoposide phosphate

Alemtuzumab

Mesna

Antineoplastic Agents, Immunological

Immunologic Factors

Antimetabolites

Immunosuppressive Agents

Antiviral Agents

Enzyme Inhibitors

Clotrimazole

Miconazole

Antifungal Agents

Calcineurin Inhibitors

Rituximab: 375 mg/m(2) intravenous (IV), day 1 for patients with cluster of differentiation 20 (CD20)-positive disease.

Cyclosporine: IV over 2 hours or orally every 12 hours on days -1 to 100, followed by a taper if graft versus host disease (GVHD) does not develop.

Allogenic stem cell transplant (ASCT)

Fludarabine:30 mg/m(2) per day IV infusion over 30 minutes, daily. On days -6, -5, -4, and -3.

Cyclophosphamide:1200 mg/m(2) per day IV infusion over 2 hours on Days 6, -5, -4, -3 Mesna: 1200 mg/m(2) per day IV infusion, Daily on days 6, -5,-4, and -3

Conditioning Chemotherapy

Tacrolimus: starting day -3 before transplant, given initially at 0.02 mg/kg/day CIV. Continue IV and then switch to an equivalent oral dose (when patient taking po) titrated for a goal level of 5 to 10 ng/ml; Sirolimus: given as an initial loading dose of 12 mg p.o. on day -3 pre-transplant, 4 mg starting day -2 pre-transplant and titrated for levels 3-12 ng/ml; Methotrexate 5 mg/m2 IV on days +1, +3, +6, and +11 post-transplant. Tacrolimus and sirolimus will be tapered at day +63, day +119 and day +180 post-transplant as tolerated.

Fludarabine:25 mg/m(2) per day IV over 30 minutes, Daily on days 1-5 Cytarabine: 2,000 mg/m(2) IV over 4 hours,on Days 1, 2, 3, 4, 5 Filgrastim: 5 mcg/kg per day subcutaneous (SC) beginning 24 hours PRIOR to initiation of chemotherapy

FLAG

Fludarabine:25 mg/m(2) per day IV infusion over 30 minutes, daily on days 1-4 Etoposide :50 mg/m(2) per day continuous IV infusion over 24 hours on days 1-4 Doxorubicin:10 mg/m(2)/day CIV, days 1-4 Vincristine:0.4 mg/m(2) per day continuous IV infusion over 24 hours daily on days 1-4 Cyclophosphamide:750 mg/m(2) IV infusion over 30 minutes on day 5

EPOCH-F

Alemtuzumab:20 mg/day IV over 8 h on days 8 to 4 pre-transplant.

Steven Z Pavletic, M.D.

Background:

Major problems with stem cell transplantation (SCT) for cancer treatment are a lack of suitable donors for patients without a human leukocyte-antigen (HLA) tissue-matched sibling and graft-versus-host disease (GVHD), a serious side effects of immune-suppressing chemotherapy that is given to bring the cancer under control before SCT. In GVHD, the patients immune system attacks the transplanted donor cells.

This study will try to improve the results of SCT from unrelated HLA-matched donors using targeted immune-depleting chemotherapy to bring the cancer under control before transplantation and to lower the chance of graft rejection, followed by reduced-intensity transplant chemotherapy to make the procedure less toxic.

Objectives:

To evaluate the safety and effectiveness of targeted immune-depleting chemotherapy followed by reduced-intensity transplant chemotherapy in patients with advanced cancers of the blood and immune system.

To evaluate the safety and effectiveness of two different drug combinations to prevent GVHD. Both regimens have been successful in preventing GVHD, but they work by different mechanisms and affect the rebuilding of the immune system after the transplant.

Eligibility:

People 18 to 74 years of age with advanced or high-risk cancers of the blood and immune system who do not have a suitable HLA-matched sibling.

Design:

All patients receive chemotherapy before transplant to treat the cancer and suppress immune function.

All patients receive a conditioning regimen of cyclophosphamide for 4 days and fludarabine for 4 days before SCT to prepare for the transplant.

Patients are randomly assigned to one of two combination drug treatments to prevent GHVD as follows:

* Group 1: Tacrolimus starting 3 days before SCT and continuing for 6 months, plus methotrexate on days 1, 3, 6, and 11 post-SCT, plus sirolimus starting 3 days before the SCT and continues for 6 months following SCT.
* Group 2: Alemtuzumab for 4 days starting 8 days before SCT, plus cyclosporine starting 1 day before SCT and continuing for 6 months.

Patients receive the donors stem cells and immune cells 2 days after completing the conditioning regimen.

Patients are followed at the clinic regularly for the first 6 months after SCT, and then less often for at least 5 years. Some visits may include bone marrow aspirates and biopsies, blood draws, and other tests to monitor disease status.

A skin biopsy, oral mucosa biopsy, and saliva collection are done to study chronic GVHD.

...

Background:

* The major limitations to the broader applicability of allogeneic hematopoietic stem cell transplantation (HSCT) for the treatment of malignancies are lack of suitable donors and therapy-related toxicities which include delayed and incomplete immune reconstitution and graft-versus-host disease (GVHD). Based on the theory that the rapid establishment of donor chimerism was essential for an optimal graft-versus-tumor effect, we have employed a strategy of targeted immune depleting chemotherapy prior to reduced-intensity allogeneic HSCT. It is our intent to investigate this approach in the setting of human leukocyte-antigen (HLA)-matched unrelated donors in a pilot manner.
* A clearly superior GVHD prophylaxis regimen has not been established in the unrelated donor transplant setting. The best results that have been reported are with the combination of alemtuzumab plus cyclosporine \[AC\] and the combination of tacrolimus, methotrexate, and sirolimus \[TMS\]. These two regimens work by mechanisms which are biologically distinct and potentially have markedly different effects upon immune reconstitution that have not been well studied. In addition, neither of these regimens has been assessed for their effects on chronic GVHD using the National Institutes of Health (NIH) Consensus Conference Criteria. It is our intent to study the effects that these two regimens have on immune reconstitution and chronic GVHD in the setting sequential targeted immune-depleting chemotherapy and reduced-intensity allogeneic HSCT from HLA-matched unrelated donors.

Objectives:

* Primary objectives:

  1. to assess the effects of two biologically distinct GVHD prophylaxis regimens, TMS and AC, on immune reconstitution in patients receiving targeted-immune depletion and reduced-intensity allogeneic HSCT from HLA-matched unrelated donors. As part of a comprehensive assessment of immune reconstitution, the primary immunologic endpoint will be the determination of cluster of differentiation 4 (CD4)+ T cell receptor V BETA repertoire by complementarity determining region 3 (CDR3) spectratyping at 3 months post-transplant.
  2. to assess overall safety of these two regimens in this setting, as determined by engraftment, acute GVHD, early and late treatment-related mortality, and overall survival.
  3. to determine and monitor incidence, organ severity and overall severity of chronic GVHD prospectively using the newly developed NIH Consensus Conference diagnosis and staging criteria and preliminarily validate those tools for use in clinical practice and trials.
* Secondary objectives include further assessment of immune reconstitution, study of engraftment kinetics, and assessment of those patients who receive higher doses of anthracyclines for long and short term toxicities

Eligibility:

* Adults (18-74 years) with advanced or high risk hematologic malignancies including acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), myelodysplastic syndrome (MDS), chronic lymphocytic leukemia (CLL), non-hodgkin lymphoma (NHL), hodgkin lymphoma (HL), chronic myelogenous leukemia (CML), multiple myeloma, and myeloproliferative disorder (MPD) who lack a suitable HLA matched sibling.
* An unrelated donor matched at a minimum of 7 of 8 alleles (HLA-A,-B,-C, and DRB1) by high resolution typing, identified through the National Marrow Donor Program.
* Life expectancy of at least 3 months, Eastern Cooperative Oncology Group (ECOG) less than or equal to 2 and relatively normal major organ functions.

Design:

* Patients will receive disease-specific induction chemotherapy (etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin (EPOCH-fludarabine (F)/rituximab (R) or fludarabine, cytarabine, and granulocyte colony-stimulating factor (FLAG)) prior to transplant for disease control and immune depletion. If disease is controlled (greater than partial response (PR)) and immune depletion objectives have been met, patients may forgo induction chemotherapy and move forward to the transplant conditioning regimen.
* All patients will receive an identical conditioning regimen consisting of cyclophosphamide 1200 mg/m(2)/day intravenous (IV) for 4 days and fludarabine 30 mg/m(2)/day for 4 days.
* Patients will be stratified according to degree of HLA-match and randomized at the time of enrollment to one of two GHVD prophylaxis regimens:

  * Group 1: Tacrolimus starting 3 days before stem cell transplant (SCT), and continuing for 6 months, plus methotrexate on days 1, 3, 6, and 11 post-SCT, plus sirolimus starting 3 days before the SCT and continues for 6 months following SCT.
  * Group 2: Alemtuzumab for 4 days starting 8 days before SCT, plus cyclosporine starting 1 day before SCT and continuing for 6 months.
* A maximum of 105 patients will be enrolled and randomly assigned to the two arms in order to yield 44 patients per arm (88 total patients) who are able to be evaluated for development of severe chronic GVHD.

Chemotherapy and Unrelated Donor Stem Cell Transplantation for Patients With Cancers of the Blood and Immune System

Phase II Trial of Targeted Immune-Depleting Chemotherapy and Reduced-Intensity Allogeneic Hematopoietic Stem Cell Transplantation Using 8/8 and 7/8 HLA-matched Unrelated Donors and Utilizing Two Graft-versus-Host Disease Prophylaxis Regimens for the Treatment of Leukemias, Lymphomas, and Pre-malignant Blood Disorders

Acute GVHD is assessed by the 1994 Consensus Conference on Acute GVHD Grading criteria. See Przepiorka D, Weisdorf D, Martin P, et al. 1994 Consensus Conference on Acute GVHD Grading. Bone Marrow Transplant. 1995; 15:825-8., for grading criteria.

Chronic GVHD is assessed by the 2005 Chronic GVHD Consensus Project. First the individual organ scoring is done, and then based on that the Global score is determined (mild-moderate-severe). See Citation: Filipovich AH, Weisdorf D, Pavletic S, et al. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biol Blood Marrow Transplant. 2005; 11:945-56., for grading criteria.

The percentage of C-C motif chemokine receptor 7 (CCR7)+CD45RA+ naïve T cells within the CD4 T cell populations was determined by flow cytometry.

The percentage of CCR7+CD45RA+ naïve T cells within the CD4 and CD8 T cell populations was determined by flow cytometry.

Ribonucleic acid (RNA) was extracted from sorted CD4 and cluster of differentiation 8 (CD8) T cells and analyzed for Vbeta repertoire by nested polymerase chain reaction (PCR) analysis using Vbeta family specific primers and a labeled constant region primer (spectratyping). The receptor repertoire diversity was calculated from spectratyping data by creating a normal standard for repertoire diversity from healthy normal controls and assessing the divergence of individual patient's T cell receptor repertoire from these standard normal donor values. In this Vbeta repertoire divergence index, lower numbers are consistent with a more normal highly diverse repertoire, and high numbers represent a highly skewed, oligoclonal repertoire. The assay is described in Memon SA et al, J Immunol Methods, 2012, 375: 84-92. The repertoire diversity of the CD4 and CD8 T cells of the donor infusion is shown for comparison.

Acute GVHD is assessed by the 1994 Consensus Conference on acute GVHD Grading criteria. See Przepiorka D, Weisdorf D, Martin P, et al. 1994 Consensus Conference on Acute GVHD Grading. Bone Marrow Transplant. 1995; 15:825-8., for grading criteria.

Here are the number of participants with adverse events. For a detailed list of adverse events, see the adverse event module.

Days to engraftment is defined as neutrophil recovery: designated by the first of 3 consecutive days with an absolute neutrophil count (ANC) above 500/mm(3).

Platelet recovery: designated by the first of 7 days where the platelet count remains above 20,000/mm(3) without transfusion support

Lymphocyte recovery: designated by the first of 3 consecutive days with absolute lymphocyte count (ALC) above 500/mm(3).

Time between the first day of transplant to the day of death.

Any death occurring within 28 days after transplantation in a patient in continuous remission.

Any death occurring 28 days or more after transplantation in a patient in continuous remission.

During depletion of lymphocytes during transplant conditioning, levels of homeostatic cytokines increase in the blood. These then decline with the expansion of new donor-derived cells. The rapidity of decline may predict acute graft versus host disease (AGVHD). Decline in cytokine IL-7 will be assessed by the enzyme-linked immunosorbent assay (ELISA).

Cluster of differentiation 3 (CD3) - cluster of differentiation 56 (CD56) + Natural Killer (NK) cells within the lymphocyte population were determined by flow cytometry. The absolute numbers of cells/µl were calculated from the absolute lymphocyte count.

Cluster of Differentiation 3 (CD3)+CD4+ and CD3+Cluster of Differentiation 8 (CD8)+ T cells within the lymphocyte population were determined by flow cytometry. The absolute numbers of cells/µl were calculated from the absolute lymphocyte count.

Cluster of differentiation 3 (CD3)+cluster of differentiation 4 (CD4)+ and CD3+CD8+ T cells within the lymphocyte population were determined by flow cytometry. The absolute numbers of cells/µl were calculated from the absolute lymphocyte count.

National Cancer Institute (NCI)

One participant was enrolled and given induction chemotherapy but was never randomized to Arm TMS or AC. Subject had one AE (infection with normal ANC or Grade 1 or 2 neutrophils: Pharynx). Subject was taken off study for disease progression and died.

TMS Arm

Rituximab: Rituximab: 375 mg/m2 IV, day 1 for patients with CD20-positive disease

Allogenic stem cell transplant (ASCT): Allogenic stem cell transplant

Conditioning Chemotherapy: Fludarabine:30 mg/m2 per day IV infusion over 30 minutes, daily On days -6, -5, -4, and -3 Cyclophosphamide:1200 mg/m2 per day IV infusion over 2 hours on Days 6, -5, -4, -3 Mesna: 1200 mg/m2 per day IV infusion, Daily on days 6, -5,-4, and -3

TMS: Tacrolimus: 0.02 mg/kg , start day 3. Continue IV or PO. Taper will begin at day +63 if no acute GVHD then at day +119 and discontinue at day +180 as tolerated Methotrexate: 5 mg/m2 IV over 15 minutes on days 1, 3, 6, and 11. Sirolimus: 12 mg PO on days -3 to 63, followed by a taper if GVHD does not develop.

FLAG: Fludarabine:25 mg/m2 per day IV over 30 minutes, Daily on days 1-5 Cytarabine: 2,000 mg/m2 IV over 4 hours,on Days 1, 2, 3, 4, 5 Filgrastim: 5 mcg/kg per day SC beginning 24 hours PRIOR to initiation of chemotherapy

A - Tacrolimus, Methotrexate, Sirolimus (TMS) Arm

AC Arm

Rituximab: Rituximab: 375 mg/m2 IV, day 1 for patients with CD20-positive disease

Cyclosporine: Cyclosporine: IV over 2 hours or orally every 12 hours on days -1 to 100, followed by a taper if GVHD does not develop.

Allogenic stem cell transplant (ASCT): Allogenic stem cell transplant

Conditioning Chemotherapy: Fludarabine:30 mg/m2 per day IV infusion over 30 minutes, daily On days -6, -5, -4, and -3 Cyclophosphamide:1200 mg/m2 per day IV infusion over 2 hours on Days 6, -5, -4, -3 Mesna: 1200 mg/m2 per day IV infusion, Daily on days 6, -5,-4, and -3

FLAG: Fludarabine:25 mg/m2 per day IV over 30 minutes, Daily on days 1-5 Cytarabine: 2,000 mg/m2 IV over 4 hours,on Days 1, 2, 3, 4, 5 Filgrastim: 5 mcg/kg per day SC beginning 24 hours PRIOR to initiation of chemotherapy EPOCH-F: Fludarabine:25 mg/m2 per day IV infusion over 30 minutes, daily on days 1-4 Etoposide :50 mg/m2 per day continuous IV infusion over 24 hours on days 1-4 Doxorubicin:10 mg/m2/d

B - Cyclosporine (AC) Arm

Rituximab:375 mg/m2 IV, day 1 for patients with CD20-positive disease. Allogenic stem cell transplant (ASCT):Conditioning Chemotherapy:Fludarabine:30 mg/m2 per day IV infusion over 30 minutes, daily On days -6, -5, -4, and -3. Cyclophosphamide:1200 mg/m2 per day IV infusion over 2 hours on Days 6, -5, -4, -3.Mesna: 1200 mg/m2 per day IV infusion, Daily on days 6, -5,-4, and -3.Tacrolimus: 0.02 mg/kg, start day 3. Continue IV or PO. Taper will begin at day +63 if no acute GVHD then at day +119 and discontinue at day +180 as tolerated. Methotrexate: 5mg/m2 IV over 15 minutes on days 1, 3, 6, and 11. Sirolimus: 12 mg PO on days -3 to 63, followed by a taper if GVHD does not develop. Sirolimus: 12 mg PO on days -3 to 63, followed by a taper if GVHD does not develop.FLAG: Fludarabine:25 mg/m2 per day IV over 30 minutes, Daily on days 1-5. Cytarabine: 2,000 mg/m2 IV over 4 hours, on Days 1, 2, 3, 4, 5. Filgrastim: 5 mcg/kg per day SC beginning 24 hours PRIOR to initiation of chemotherapy

Tacrolimus, Methotrexate, Sirolimus (TMS) Arm

Rituximab375 mg/m2 IV, day 1 for pts with CD20-positive disease. Cyclosporine IV over 2 hrs or orally every 12 hrs on days -1-100, followed by a taper if GVHD does not develop. Allogenic stem cell transplant. Conditioning Chemotherapy Fludarabine:30 mg/m2 per day IV infusion over 30 min., daily on days -6, -5, -4, and -3. Cyclophosphamide1200 mg/m2 per day IV infusion over 2 hrs on Days 6, -5, -4, -3. Mesna1200 mg/m2 per day IV infusion, Daily on days 6, -5,-4, and -3. FLAG: Fludarabine25 mg/m2 per day IV over 30 min., Daily on days 1-5. Cytarabine 2,000 mg/m2 IV over 4 hrs, on Days 1, 2, 3, 4, 5. Filgrastim 5 mcg/kg per day SC beginning 24 hrs PRIOR to start of chemotherapy. EPOCH-F: Fludarabine25 mg/m2 per day IV infusion over 30 min., daily on days 1-4. Etoposide 50 mg/m2 per day continuous IV infusion over 24 hrs on days 1-4. Doxorubicin10 mg/m2/d. Grp 2 Alemtuzumab for 4 days starting 8 days before SCT + cyclosporine starting 1 day before SCT and continuing for 6 months.

Cyclosporine (AC) Arm

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Non Hodgkin's Lymphoma (NHL)

Hodgkin's Lymphoma (HL)

Chroni Lymphocytic Leukemia (CLL)

AML/MDS

Chronic Myeloid Leukemia (CML)

CTCL/PTCL

Acute Lymphoblastic Leukemia (ALL)

Multiple Myeloma (MM)

Other

Acute Myeloid Leukemia (AML)/Myelodysplastic Syndrome (MDS); Cutaneous T Cell Lymphoma (CTCL)/Peripheral T Cell Lymphoma (PTCL)

Histology

There were 89 participants in the study. 3 patients enrolled and their cancers progressed prior to randomization so they were taken off study. 3 of these participants went back into remission with additional chemo and were re-enrolled on the protocol and randomized. They are counted twice in the enrolment (e.g. 92) but only once in the Started row.

Dr. Steven Z. Pavletic

2 of 44 patients who completed the AC arm were transplanted after our cutoff for data analysis and are not included.

Percentage of Participants With Grade II-IV Acute Graft Versus Host Disease (GVHD)

Moderate or Severe cGVHD

Severe cGVHD

Percentage of Participants With Chronic Graft Versus Host Disease (cGVHD)

6 mo (TMS=28; AC= 28)

12 mo (TMS=25; AC= 21)

24 mo (TMS=18; AC= 13)

A few measurements were missed, one patient was not evaluable for technical reasons and removed from the analysis, but most of the decline was due to patients that had gone off study.

Recovery of Naïve Cluster of Differentiation 4 (CD4) T Cells

Recovery of Naïve Cluster of Differentiation 8 (CD8) T Cells

1 month

3 months

6 mo (TMS=7; AC= 9)

12 mo (TMS=7; AC=9)

Donor CD4 cells (TMS=8; AC=8)

Rituximab: 375 mg/m2 intravenous (IV), day 1 for patients (pts) with cluster of differentiation 20-positive disease. Allogenic stem cell transplant (txplt). Fludarabine:30 mg/m2 per day IV over 30 min. daily. On days -6, -5, -4, and -3. Cyclophosphamide:1200 mg/m2 per day IV over 2 hrs on Days 6, -5, -4, -3. Mesna:1200 mg/m2 per day IV, Daily on days 6, -5,-4, and -3.Tacrolimus: day -3 before txplt, 0.02 mg/kg/day CIV, then switch to an equivalent oral dose (when pts taking po) titrated for a goal level of 5-10 ng/ml; Sirolimus: loading dose of 12 mg p.o. on day -3 pre-txplt, 4 mg day -2 pre-txplt and titrated for levels 3-12 ng/ml; Methotrexate 5 mg/m2 IV on days +1, +3, +6, and +11 post txplt). Tacrolimus and sirolimus will be tapered at day +63, day +119 and day +180 post-txplt as tolerated. Fludarabine:25 mg/m2 per day IV over 30 minutes, Daily on days 1-5.Cytarabine: 2,000 mg/m2 IV over 4 hrs, on Days 1, 2, 3, 4, 5. Filgrastim: 5 mcg/kg per day SC beginning 24 hrs before chemo.

The original intention was to perform these assays on the first 10 pts within each arm. One pt died within the first mo., others died within the 1st yr. Not all donors gave consent for research analyses to be done on their cells, hence cells from those donors were not available.

Changes in Cluster of Differentiation 4 (CD4) T Cell Receptor Vbeta Repertoire

12 mo (TMS=7; AC= 9)

Donor CD8 cells (TMS=8; AC= 8)

Changes in CD8 T Cell Receptor Vbeta Repertoire

Percentage of Participants With Grade III-IV Acute Graft Versus Host Disease (GVHD)

Toxicities

B - Cyclosporine (AC Arm)

One myeloma patient had graft failure in the AC Arm. 2 of 44 patients who completed the AC arm were transplanted after our cutoff for data analysis and are not included.

Days to Engraftment of Neutrophils

Days to Engraftment of Platelets

Days to Engraftment of Lymphocytes

Overall Survival

B - Cyclosporine (C) Arm

Early Treatment Related Mortality

Percentage of Participants With Late Treatment Related Mortality

Following the focus on chronic graft-versus host disease (GVHD) as a primary outcome measure in 2011, this measure was not assessed.

Decline in Homeostatic Cytokine Interleukin 7 (IL-7) Post-Transplant

2 weeks

6 months

12 months

24 months

TMS Arm Rituximab: 375 mg/m2 IV, day 1 for patients with cluster of differentiation 20 (CD20)-positive disease Allogenic stem cell transplant (ASCT):Allogenic stem cell transplant Conditioning Chemotherapy:Fludarabine:30 mg/m2 per day IV infusion over 30 minutes, daily. On days -6, -5, -4, and -3 Cyclophosphamide:1200 mg/m2 per day IV infusion over 2 hours on Days 6, -5, -4, -3 Mesna:1200 mg/m2 per day IV infusion, Daily on days 6, -5,-4, and -3 TMS: Tacrolimus: 0.02 mg/kg, start day 3. Continue IV or PO. Taper will begin at day +63 if no acute GVHD then at day +119 and discontinue at day +180 as tolerated Methotrexate: 5 mg/m2 IV over 15 minutes on days 1, 3, 6, and 11 Sirolimus: 12 mg PO on days -3 to 63, followed by a taper if GVHD does not develop.

FLAG: Fludarabine:25 mg/m2 per day IV over 30 minutes, Daily on days 1-5 Cytarabine: 2,000 mg/m2 IV over 4 hours, on Days 1, 2, 3, 4, 5 Filgrastim: 5 mcg/kg per day SC beginning 24 hours PRIOR to initiation of chemotherapy

2 of 44 patients who completed the AC arm were transplanted after our cutoff for data analysis and are not included. A total of 5 completed participants did not contribute data due to missing samples, and participants who died and were not able to supply samples for the time points indicated.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
TMS for the Treatment of Pancreatic Cancer Pain	NCT00324428	Pain Visceral Pain Pancreatic Canc...	Transcranial Ma...	18 Years - 65 Years	Beth Israel Deaconess Medical Center
Chemotherapy and Unrelated Donor Stem Cell Transplantation for Patients With Cancers of the Blood and Immune System	NCT00520130	Myelodysplastic... Hodgkin's Lymph... Non-Hodgkin's D... Acute Leukemia Multiple Myelom...	Rituximab Cyclosporine Allogenic stem ... Conditioning Ch... TMS FLAG EPOCH-F Alemtuzumab	18 Years - 74 Years	National Institutes of Health Clinical Center (CC)
Chemotherapy and Unrelated Donor Stem Cell Transplantation for Patients With Cancers of the Blood and Immune System	NCT00520130	Myelodysplastic... Hodgkin's Lymph... Non-Hodgkin's D... Acute Leukemia Multiple Myelom...	Rituximab Cyclosporine Allogenic stem ... Conditioning Ch... TMS FLAG EPOCH-F Alemtuzumab	18 Years - 74 Years	National Institutes of Health Clinical Center (CC)
TMS Electrochemotherapy for Glioblastoma Multiforme	NCT02283944	Glioblastoma	TMS	18 Years -	University of Aarhus
Effect of Lamotrigine on Cognition in NF1	NCT02256124	Neurofibromatos...	Lamotrigine Placebo	12 Years - 18 Years	Erasmus Medical Center
Study of Palifermin (Kepivance) in Persons Undergoing Unrelated Donor Allogeneic Hematopoietic Cell Transplantation	NCT02356159	Myelodysplastic... Hodgkin's Lymph... Non-Hodgkin's L... Acute Leukemia Multiple Myelom...	Rituximab Conditioning ch... TMS FLAG EPOCH-F Hematopoietic s... Palifermin	18 Years -	National Institutes of Health Clinical Center (CC)
TMS Electrochemotherapy for Glioblastoma Multiforme	NCT02283944	Glioblastoma	TMS	18 Years -	University of Aarhus

Spots Global Cancer Trial Database for tms

Every month we try and update this database with for tms 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 tms

Every month we try and update this database with for tms 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 tms 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.