Symptoms and General Pathology

All Conditions

Neoplasms

Blood and Lymph Conditions

Immune System Diseases

Rare Diseases

Syndrome

Leukemia

Leukemia, Myeloid

Myeloproliferative Disorders

Preleukemia

Myelodysplastic Syndromes

Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Neoplasms by Histologic Type

Hematologic Diseases

Bone Marrow Diseases

Precancerous Conditions

Chronic Disease

Disease Attributes

Myelodysplastic-Myeloproliferative Diseases

Chronic Graft Versus Host Disease

Chronic Myeloid Leukemia

Chronic Myeloproliferative Disorders

Myelodysplastic/myeloproliferative Disease

Antineoplastic Agents

Antirheumatic Agents

All Drugs and Chemicals

Anti-Infective Agents

Cyclophosphamide

Fludarabine

Fludarabine phosphate

Mycophenolic Acid

Tacrolimus

Thymoglobulin

Busulfan

Immunosuppressive Agents

Antineoplastic Agents, Alkylating

Immunologic Factors

Alkylating Agents

Antimetabolites

Calcineurin Inhibitors

Enzyme Inhibitors

Anti-Bacterial Agents

Antibiotics, Antitubercular

Antitubercular Agents

Days -7 through -2: Fludarabine 30 mg/m2/day iv x 6 days Days -6 through -5 Busulfan 1 mg/kg po qid x 2 days Days -4 through -3 Thymoglobulin 2,5 mg/kg po qd x 2 days Days -1 through +30: Mycophenolate mofetil 30 mg/kg/day, maximum 2 g/day, iv or po x 30 days Days -1 through +150: Tacrolimus 0.03 mg/kg/day with further correction by concentration

Days -7 through -2: Fludarabine 30 mg/m2/day iv x 6 days Days -4 through -3: Busulfan 1 mg/kg po qid x 2 days Day 0: Infusion of unmanipulated graft Day +3 and +4: Cyclophosphamide 50 mg/kg/day iv Days +5 through +35: Mycophenolate mofetil 30 mg/kg/day, maximum 2 g/day, iv or po x 30 days Days +5 through +120: Tacrolimus 0.03 mg/kg/day with further correction by concentration

Unrelated allogeneic stem cell transplantation

Fludarabine monophosphate

Mycophenolate mofetil

Boris V. Afanasyev, Professor

Purpose There is a growing evidence of high efficacy of post-transplantation cyclophocphomide (PTCy)-based GVHD prophylaxis in haploidentical and matched related and unrelated bone marrow transplantation. There is limitted, but growing data on safety and efficacy of this prophylaxis in unrelated and peripheral blood stem cell transplantations. Use of PTCy in chronic myeloproliferative neoplasms and myelodisplatic syndrome is of particular interest. On the one hand, PTCy could reduce the incidence of chronic GVHD and long-term bormidity. On the other hand, there is a concern, that PTCy can increase the incidence of graft failures in this group of patients. Currently published data indicate that low-dose Thymoglobulin-based prophylaxis is the most promissing compatitor in terms of acute and chronic GVHD control. So there is a rationale to randomize Thymoglobulin and PTCy as GVHD prophilaxis. Pre-transplant assesment of moratlity (PAM)-index will be used as the strata for randomization, as it is the paramter that takes into account the most important factors effecting survival. The conditioning regimen and the other two components of GVHD prophylaxis (mycophenolate mofetil and tacrolimus) will be identical in the two arms of the study.

Trial of GVHD Prophylasxis With PTCy or Thymoglobulin in Unrelated SCT

Randomized Trial of GVHD Prophylasxis With Post-transplantation Cyclophocphomide (PTCy) or Thymoglobulin in Unrelated SCT Recepients With Chronic Myeloproliferative Neoplasms and Myelodisplatic Syndrome

Toxicity parameters based on NCI CTCAE 4.03 grades: hepatotoxicity (liver function tests), nephrotoxicity (creatinine), neurotoxicity (attending physician assessment), mucositis (attending physician assessment), hemorrhagic cystitis (attending physician assessment), cardiotoxicity (ECG, echocardiography). Additional toxicity parameters: incidence and severity of veno-occlusive disease, incidence of transplant-associated microangiopathy

St. Petersburg State Pavlov Medical University

Head of adolescent and adult department of oncology, heamatology and transplantation

Leukemia, Myeloid, Acute

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Lymphoma

Leukemia, Lymphocytic, Chronic, B-Cell

Graft vs Host Disease

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Leukemia, B-Cell

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Lymphosarcoma

Chronic Lymphocytic Leukemia

Homologous Wasting Disease

Acute Graft Versus Host Disease

Days -8 through -4: Busulfan 1 mg/kg po qid x 4 days Days -3 through -2: Cyclophosphamide 50mg/kg/day iv x 2 days Or Days -7 through -2: Fludarabine 30 mg/m2/day iv x 6 days Days -4 through -3: Busulfan 1 mg/kg po qid x 2 days Day 0: Infusion of unmanipulated graft Day +3 and +4: Cyclophosphamide 50 mg/kg/day iv

Days -8 through -4: Busulfan 1 mg/kg po qid x 4 days Days -3 through -2: Cyclophosphamide 50mg/kg/day iv x 2 days Or Days -7 through -2: Fludarabine 30 mg/m2/day iv x 6 days Days -4 through -3: Busulfan 1 mg/kg po qid x 2 days Day 0: Infusion of unmanipulated graft Day +3 and +4: Cyclophosphamide 50 mg/kg/day iv Days +5 through +35: Mycophenolate mofetil 30 mg/kg/day, maximum 2 g/day, iv or po x 30 days Days +5 through +120: Tacrolimus 0.03 mg/kg/day with further correction by concentration

Days -8 through -4: Busulfan 1 mg/kg po qid x 4 days Days -3 through -2: Cyclophosphamide 50mg/kg/day iv x 2 days Or Days -7 through -2: Fludarabine 30 mg/m2/day iv x 6 days Days -4 through -3: Busulfan 1 mg/kg po qid x 2 days Day 0: Infusion of unmanipulated graft Day +3 and +4: Cyclophosphamide 50 mg/kg/day iv Days +5 through +35: Mycophenolate mofetil 45 mg/kg/day, maximum 3 g/day, iv or po x 30 days Days +5 through +120: Tacrolimus 0.03 mg/kg/day with further correction by concentration

Allogeneic hematopoietic stem cell transplantation

Boris V Afanasyev, MD, Prof.

This study evaluates the efficacy of high-dose post-transplantation cyclophosphomide as graft-versus-host disease (GVHD) prophylaxis after allogeneic stem cell transplantation in patients with different risk of GVHD. The risk-adapted strategy involves using single-agent cyclophosphomide in recipients of matched bone marrow graft, and combining cyclophosphomide with tacrolimus and mycophenolate mofetil in recipients of matched peripheral blood stem cells and mismatched bone marrow.

Post-transplantation Cyclophosphamide as GVHD Prophylaxis After HSCT

High-dose Post-transplantation Cyclophosphamide as Graft Versus-host Disease Prophylaxis After Allogeneic Hematopoietic Stem Cell Transplantation

Ivan S Moiseev

Vice-director for science of R.M. Gorbacheva Memorial Institute of Hematology, Oncology and Transplantation

Heart and Blood Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Hodgkin Disease

Lymphoma, Non-Hodgkin

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hemorrhagic Disorders

Hodgkin Lymphoma

Dermatologic Agents

Reproductive Control Agents

Micronutrients

Hematinics

Vitamins

Methotrexate

Lenograstim

Folic Acid

Vitamin B Complex

Folic Acid Antagonists

Folinic Acid

Folate

Vitamin B9

Fludarabine administered by vein at dose of 40 mg/m2 in 100 ml of normal saline (NS) on Days -6 through -3.

First two doses of Busulfan, 80 mg/m2 administered as an outpatient or as an inpatient to facilitate for this pharmacokinetically directed therapy. Busulfan is administered at the dose calculated to achieve a total (including first two doses delivered on day -13 and -12) systemic exposure of 20,000 ± 12% µMol-min based on the pharmacokinetic studies.

First two doses of Busulfan, 80 mg/m2 administered as an outpatient or as an inpatient to facilitate for this pharmacokinetically directed therapy. Busulfan is administered at the dose calculated to achieve a total (including first two doses delivered on day -13 and -12) systemic exposure of 20,000 ± 12% µMol-min based on the pharmacokinetic studies.

Fresh or cryopreserved bone marrow or peripheral blood progenitor cells infused on Day 0.

Stem Cell Infusion

Starting dose of 0.015 mg/kg (ideal body weight) as 24 hour continuous infusion daily adjusted to achieve therapeutic level of 5-15 ng/ml. Tacrolimus changed to oral dosing when tolerated and can be tapered off after day +90 if no graft versus host disease (GVHD) present.

5 mg/m2 by vein on Days 1, 3, 6 and 11 post transplant.

5 mcg/kg/day subcutaneously beginning on Day +7, and continuing until absolute neutrophil count (ANC) is \> 500 \* 10/L for 3 consecutive days.

G-CSF

Uday Popat, MD

The goal of this clinical research study is to learn if giving busulfan and fludarabine before a stem cell transplant can help control the disease better than the standard method in patients with leukemia, lymphoma, multiple myeloma, MDS, or MPD. In this study, 2 doses of busulfan will be given 2 weeks before a stem cell transplant followed by 4 doses of busulfan and fludarabine during the week before the stem cell transplant, rather than the standard method of giving 4 doses of busulfan and fludarabine only during the week before the stem cell transplant.

The safety of this combination therapy will also be studied.

Busulfan is designed to kill cancer cells by binding to DNA (the genetic material of cells), which may cause cancer cells to die. Busulfan is commonly used in stem cell transplants.

Fludarabine is designed to interfere with the DNA of cancer cells, which may cause the cancer cells to die.

Central Venous Catheter:

If you choose to take part in this study, the chemotherapy, some of the other drugs in this study, and the stem cell transplant will be given by vein through your central venous catheter (CVC). A CVC is a sterile flexible tube and needle that will be placed into a large vein while you are under local anesthesia. Blood samples will also be drawn through your CVC. The CVC will remain in your body during treatment. Your doctor will explain this procedure to you in more detail, and you will be required to sign a separate consent form.

Study Drug Administration and Procedures:

For a stem cell transplant, the days before you receive your stem cells are called minus days. The day you receive the stem cells is called Day 0. The days after you receive the stem cells are called plus days.

You will receive a dose of busulfan by vein over about 3 hours on Day -13 and Day -12. With the Day -13 busulfan infusion, about 11 samples of blood (about 1-2 teaspoons each time) will be drawn for pharmacokinetic (PK) testing at various time points before and after you receive your first dose of busulfan. The study staff will tell you the blood testing schedule. PK testing measures the amount of study drug in the body at different time points. The PK testing will help the doctor decide your dose of busulfan for Days -6 through -3. If needed, PK blood testing may also be done on Day -6 during your dose of Busulfan. You may receive the Day -13 and Day -12 busulfan dose either as an outpatient in the clinic or as an inpatient in the hospital.

A heparin lock line will be placed in your vein to lower the number of needle sticks needed for these draws. If it is not possible for the PK tests to be performed for technical reasons, you will be taken off study and receive the standard fixed dose of busulfan.

On Days -13 and -12, you will receive busulfan by vein over 3 hours.

On Days -11 through -7, you will rest.

On Days -6 through -3, you will receive fludarabine by vein over 1 hour, then busulfan by vein over 3 hours.

On Days -2 and -1, you will rest.

On Day 0, you will receive the stem cell transplant by vein.

After the transplant, you will receive tacrolimus, methotrexate, or other drugs to weaken the immune system in the standard manner to lower the risk of graft-vs-host disease (GVHD), a reaction of the donor's immune cells against the recipient's body.

You will receive tacrolimus by vein as a nonstop infusion until you are able to take it by mouth to help lower the risk of GVHD. You will then take tacrolimus by mouth 2 times a day for about 3 months. After that, your tacrolimus dose may be lowered if you do not have GVHD. Your doctor will discuss this with you. On Days 1, 3, and 6, if your stem cells are from a related or matched unrelated donor, you will receive methotrexate over 30 minutes each day by vein to help lower the risk of GVHD. Participants receiving a matched unrelated donor will also receive methotrexate on Day 11 after the transplant.

You will receive filgrastim as an injection under the skin 1 time a day, starting 1 week after the transplant, until your blood cell levels return to normal. Filgrastim is designed to help with the growth of white blood cells.

Study Testing:

While you are in the hospital, you will be checked for any side effects as part of your standard of care. Blood (about 2 teaspoons) will be drawn every day to check for side effects, for routine tests, to check your blood counts, kidney and liver function, and to check for infections.

As part of standard care, you will remain in the hospital for about 3-4 weeks after the transplant. After you are sent home from the hospital, you must remain in the Houston area to be checked for infections and other transplant side effects until about 3 months after transplant. During this time, you will return to the clinic at least 1 time each week. The following tests and procedures will be performed:

* You will be asked about how you are feeling and about any side effects you may be having.
* Blood (about 2 teaspoons) will be drawn for routine tests.

About 1, 3, 6, and 12 months after the transplant:

* You will have a physical exam, including measurement of your vital signs (blood pressure, heart rate, temperature, and breathing rate).
* You will be asked about how you are feeling and about any side effects you may be having.
* Blood (about 5 teaspoons) will be drawn to see how well the transplant has "taken."
* You will have a bone marrow aspiration to check the status of the disease, if your doctor thinks it is needed. To collect a bone marrow aspiration, an area of the hip or other site is numbed with anesthetic, and a small amount of bone marrow is withdrawn through a large needle.

Length of Study:

You will be taken off study 3 years after the end of treatment. You may be taken off study early if the disease gets worse, if you have any intolerable side effects, of if you are unable to follow study directions.

You should talk to the study doctor if you want to leave the study early. If you are taken off study early, you still may need to return for routine follow-up visits after the transplant, if your transplant doctor decides it is needed.

It may be life-threatening to leave the study after you have begun to receive the study drugs but before you receive the stem cells.

This is an investigational study. Busulfan and fludarabine are both FDA approved and commercially available. The investigational part of this study is the addition of 2 more doses of busulfan.

Up to 200 patients will take part in this study. All will be enrolled at MD Anderson.

Allogeneic Transplantation Using Timed Sequential Busulfan and Fludarabine Conditioning

Phase II Study of Timed Sequential Busulfan in Combination With Fludarabine in Allogeneic Stem Cell Transplantation

Number of participants expired within the first 100 days after transplant not due to relapsed disease.

Number of participants that are disease free and alive one year post transplant.

Number of participants that were diseased free and alive 3 years post-transplant.

M.D. Anderson Cancer Center

Allogeneic stem cell transplant for patients with hematologic malignancies: The randomization was stratified equally for the first 100 patients at study entry and conditioned regimen with Fludarabine/Timed sequential Busulfan AUC 16,000umol/l vs. Fludarabine/Timed Sequential (TS) Busulfan AUC 20,000umol/l.

Arm 1: Participants w/Hematologic Malignancies Treated w/Fludarabine/TS Busulfan AUC 16,000 Umol/l

Arm 2: Participants w/Hematologic Malignancies Treated w/Fludarabine/TS Busulfan AUC 20,000umol/l.

Total

Age, Categorical

Sex: Female, Male

Race (NIH/OMB)

United States

Saudi Arabia

Region of Enrollment

Uday Popat, M.D. / Stem Cell Transplantation

Allogeneic stem cell transplant for patients with hematologic malignancies: The randomization was stratified equally for the first 100 patients at study entry and conditioned regimen with Fludarabine/Timed Sequential (TS) Busulfan AUC 16,000umol/l vs. Fludarabine/Timed sequential Busulfan AUC 20,000umol/l.

Non-Relapse Mortality Rate (NRM)

Overall Survival

Overall Study

Leukemia, Biphenotypic, Acute

Acute Leukemia of Ambiguous Lineage

Bendamustine Hydrochloride

10 patients Days -7 through -2: Fludarabine 30 mg/m2/day iv x 6 days Days -6 through -3: Busulfan 1 mg/kg po qid №14 Day 0: Infusion of unmanipulated graft Day +3 and +4: Bendamustine 140 mg/m2/day iv.

10 patients Days -7 through -2: Fludarabine 30 mg/m2/day iv x 6 days Days -6 through -3: Busulfan 1 mg/kg po qid №14 Day 0: Infusion of unmanipulated graft Day +3 and +4: Bendamustine 100 mg/m2/day iv

10 patients Days -7 through -2: Fludarabine 30 mg/m2/day iv x 6 days Days -6 through -3: Busulfan 1 mg/kg po qid №14 Day 0: Infusion of unmanipulated graft Day +3, +4: Bendamustine 70 mg/m2/day iv.

Allogeneic stem cell transplantation

Bendamustine

Several groups have demonstrated very low incidence of acute and chronic graft-versus-host disease (GVHD) with post-transplantation cyclophosphamide (PTCy) in haploidentical, unrelated and related allogeneic stem cell transplantation (SCT). Nonetheless for majority of the grafts, except for 10/10 HLA-matched bone marrow, with this type of prophylaxis require concomitant administration of calcineurin inhibitors±MMF, which delays immune reconstitution and development of graft-versus-leukemia (GVL) effect. So, despite reduction of transplant-related mortality, use of PTCy doesn't lead to the reduction of relapse incidence. This is particularly important for relapsed or refractory acute leukemia patients, where, despite all efforts to intensify conditioning regimens, relapses after SCT occur in more than 50% of patients, and long-term survival rarely exceeds 10-20%. In preclinical model of haploidentical SCT the substitution of post-transplantation cyclophosphamide with bendamustine, led to comparable GVHD control, but significantly augmented GVL effect. To test this hypothesis and improve the outcome of allogeneic SCT in refractory acute leukemia patients we initiated a pilot trial with high-dose post-transplantation bendamustine for GVHD prophylaxis. The selection of doses is based on the previous dose-escalation studies. Additional immunosuppression could be added for mismatched grafts.

GVHD Prophylaxis With Post-transplantation Bendamustine in Refractory Leukemia

Dose-escalation Study of Graft-versus-host Disease Prophylaxis With High-dose Post-transplantation Bendamustine in Patients With Refractory Acute Leukemia

Consultations are ongoing about how IPD initiative fits the local law "About personal data 152-fz".

Engraftment is defined as the first of 3 consecutive days with an ANC\>500 per μl and WBC\>1000 per μl. Platelet engraftment is not mandatory for the endpoint.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Trial of GVHD Prophylasxis With PTCy or Thymoglobulin in Unrelated SCT	NCT02627573	Leukemia, Chron... Myelodysplastic... Leukemia, Myelo...	Unrelated allog... Busulfan Fludarabine mon... Tacrolimus Mycophenolate m... Cyclophosphamid... Thymoglobulin	18 Years - 75 Years	St. Petersburg State Pavlov Medical University
Post-transplantation Cyclophosphamide as GVHD Prophylaxis After HSCT	NCT02294552	Acute Myeloid L... Acute Lymphoid ... Lymphoma Myelodysplastic... Chronic Lymphoc... Immune System D...	Cyclophosphamid... Busulfan Fludarabine mon... Tacrolimus Mycophenolate m... Allogeneic hema...	18 Years - 65 Years	St. Petersburg State Pavlov Medical University
Allogeneic Transplantation Using Timed Sequential Busulfan and Fludarabine Conditioning	NCT01572662	Leukemia Acute Myeloid L... Acute Lymphocyt... Chronic Myeloid... Chronic Lymphoc... Myeloproliferat... Non-Hodgkins Ly... Hodgkins Lympho... Multiple Myelom... Myelodysplastic...	Fludarabine mon... Busulfan Stem Cell Infus... Tacrolimus Methotrexate G-CSF	5 Years - 75 Years	M.D. Anderson Cancer Center
GVHD Prophylaxis With Post-transplantation Bendamustine in Refractory Leukemia	NCT02799147	Leukemia, Acute... Acute Myeloid L... Mixed-Lineage A...	Allogeneic stem... Fludarabine mon... Busulfan Bendamustine	18 Years - 60 Years	St. Petersburg State Pavlov Medical University

Spots Global Cancer Trial Database for fludarabine monophosphate