Acute Lymphoblastic LeukemiaPhase 1NCT00686556
Total Marrow Irradiation for Refractory Acute Leukemia
A Phase 1 study testing cyclophosphamide, cyclosporine and Fludarabine in people with Acute Lymphoblastic Leukemia and Myelodysplastic Syndrome, run by Masonic Cancer Center, University of Minnesota at 1 site in United States.
Trial summary
RATIONALE: Giving chemotherapy and total marrow irradiation before a donor umbilical cord blood or hematopoietic stem cell transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. Read more about this study
- Who is it for?
- Ages Up to 55 years
- Conditions the study is for
- Acute Lymphoblastic Leukemia, Myelodysplastic Syndrome, Multiple Myeloma
- What is being tested?
- cyclophosphamide, cyclosporine and Fludarabine
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2012to Dec 2016
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 55 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Acute lymphoblastic leukemia
- ≥ Complete remission 2 (CR2) (adults ≥ 18 years and ≤ 55 years)
- CR2 in pediatrics (defined as <18 years) and <12 months duration of first remission
- ≥ CR3 or not in remission (pediatric patients <18 years)
- T cell leukemia ≥ CR2
- Evidence of pre-transplant minimal residual disease (MRD) by flow cytometry, FISH or cytogenetics
Show all 31Show fewer
- Myelodysplastic syndrome
- ≤ 55 years of age and ≥ 10% blasts, not responsive to hypomethylating agents and/or conventional therapy
- Acute myeloid leukemia
- Not in remission (pediatric patients <18 years)
- Not in remission (10-30% blasts in the bone marrow for adult patients ≥18 years and ≤ 55 years)
- Evidence of pre-transplant minimal residual disease (MRD) by flow cytometry, FISH or cytogenetics
- Multiple myeloma
- No prior autologous transplant and fitting into one of the following disease categories:
- Early disease stage (CR1/PR1) with high-risk molecular features
- Early disease stage (CR1/PR1) with high-risk clinical features
- Late disease stage (CR2/PR2+) with high-risk clinical features
- Other high risk hematologic malignancies - to be approved by 2 or more hematology/oncology and BMT physicians
- Patients with prior CNS involvement are eligible provided that it has been treated and is in remission. CNS therapy (chemotherapy or radiation) should continue as medically indicated during the protocol.
- Have acceptable organ function within 14 days of study registration defined as:
- Renal: glomerular filtration rate > 60ml/min/1.73m2
- Hepatic: bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), Alkaline phosphatase (ALP) < 5 x upper limit of normal (ULN)
- Pulmonary function: Carbon Monoxide Diffusing Capacity corrected (DLCOcorr) > 50% of normal, (oxygen saturation [>92%] can be used in child where pulmonary function tests (PFT's) cannot be obtained)
- Cardiac: left ventricular ejection fraction ≥ 45% by echocardiogram (ECHO) or multi gated acquisition scan (MUGA)
- Karnofsky performance status (PS) >80% for ages 16 years and older or Lansky Play Score >50 for < 16 years
- An acceptable source of stem cells according to current University of Minnesota BMT program guidelines:
- UCB graft will be composed of two partially HLA matched units. Each unit must be matched at 4-6 HLA loci to the recipient and to each other. If two matched units are not available, then a single HLA 4-6 matched unit may be used if of adequate cell dose - total graft dose must be >3 x 107 MNC/kg
- HLA-matched related donor (6/6 or 5/6 antigen match)
- HLA-matched unrelated adult donor (if previously identified)
- Women of childbearing potential must agree to use adequate contraception (diaphragm, birth control pills, injections, intrauterine device [IUD], surgical sterilization, subcutaneous implants, or abstinence, etc.) for the duration of treatment.
- Voluntary written consent
Who cannot join
- Active uncontrolled infection at time of enrollment or documented fungal infection within 3 months.
- Evidence of Human immunodeficiency virus (HIV) infection
- Pregnant or breast feeding. The agents used in this study may be teratogenic to a fetus and there is no information on the excretion of agents into breast milk. All females of childbearing potential must have a blood test or urine study within 2 weeks prior to registration to rule out pregnancy.
- Prior myeloablative transplant within the last 6 months
- Prior total body irradiation (TBI) making total marrow irradiation (TMI) not feasible
Trial locations and contacts
1 site in 1 country.
United States1 site
Masonic Cancer Center at University of Minnesota
Minneapolis, Minnesota, 55455
About this study
Official title: Total Marrow Irradiation and Myeloablative Chemotherapy Followed By Double Umbilical Cord BloodTransplantation In Patients With Refractory Acute Leukemia
RATIONALE: Giving chemotherapy and total marrow irradiation before a donor umbilical cord blood or hematopoietic stem cell transplant helps stop the growth of cancer cells. It may also 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 cyclosporine and mycophenolate mofetil after the transplant may stop this from happening.
PURPOSE: This phase I trial is studying the side effects and best dose of total marrow irradiation when given together with combination chemotherapy and umbilical cord blood hematopoietic stem cell transplant in treating patients with acute leukemia, acute myeloid leukemia or multiple myeloma that did not respond to previous therapy.
Read the detailed description
OBJECTIVES:
Primary
- Determine the maximum tolerated dose of total marrow irradiation (TMI) delivered by image-guided tomographic intensity-modulated radiotherapy when administered in combination with myeloablative chemotherapy in patients undergoing double umbilical cord blood (UCB) transplantation or hematopoietic stem cell for refractory acute leukemia.
Secondary
- Determine the incidence of engraftment (defined as achievement of neutrophil count > 500/uL at 42 days after transplantation).
- Determine the incidence of platelet engraftment at 6 months and at 1 year after transplantation.
- Evaluate the incidence of complete donor chimerism and the relative contribution of each UCB unit to donor engraftment within the first 100 days after transplantation.
- Determine the incidence of transplantation-related mortality (TRM) at 6 months after treatment with a TMI-containing myeloablative conditioning regimen.
- Determine the incidence of grade II-IV and grade III-IV acute graft-versus-host disease (GVHD) at 100 days after transplantation.
- Determine the incidence of chronic GVHD at 1 year after transplantation.
- Determine the incidence of relapse at 1 year after transplantation.
- Determine the survival and disease-free survival at 1 and 2 years after transplantation.
- Assess the durability of remission based on presence of rapid early response (defined by clearance of leukemic blasts from the bone marrow at 21 days after transplantation).
OUTLINE: This is a dose-escalation study of total marrow irradiation (TMI).
- Myeloablative conditioning regimen: Patients receive fludarabine phosphate IV over 1 hour once daily for 3 days between days -12 and -6 and cyclophosphamide IV once daily for 2 days between days -11 and -6. Patients undergo TMI once daily for 4-8 days between days -8 and -1.
- Donor umbilical cord blood (UCB) transplantation: Patients undergo single-unit or double-unit donor UCB transplantation on day 0. Patients receive filgrastim (G-CSF) IV or subcutaneously once daily beginning on day 1 and continuing until blood counts recover.
- Related Donor: Related donor bone marrow will be collected (target cell dose 5x10^8 nucleated cells/kg recipient weight, minimum 3x10^8 nucleated cells/kg recipient weight) and infused without processing on day 0.
- Graft-versus-host disease (GVHD) prophylaxis: Patients receive cyclosporine IV over 2 hours or orally 2-3 times daily beginning on day -3 and continuing until day 100, followed by a taper until day 180, in the absence of GVHD. Patients also receive mycophenolate mofetil IV or orally 2-3 times daily beginning on day -3 and continuing until day 30 (or 7 days after engraftment), in the absence of acute GVHD.
Patients are followed periodically for up to 2 years after transplantation.
- Being tested
- cyclophosphamide, cyclosporine, Fludarabine, mycophenolate mofetil, total marrow irradiation
- Keywords
- recurrent adult acute lymphoblastic leukemia, recurrent childhood acute lymphoblastic leukemia, recurrent adult acute myeloid leukemia, recurrent childhood acute myeloid leukemia, adult acute myeloid leukemia with 11q23 (MLL) abnormalities, adult acute myeloid leukemia with inv(16)(p13;q22), adult acute myeloid leukemia with t(15;17)(q22;q12), adult acute myeloid leukemia with t(16;16)(p13;q22), adult acute myeloid leukemia with t(8;21)(q22;q22), ALL, MDS
- Medical subject headings
- Precursor Cell Lymphoblastic Leukemia-Lymphoma, Myelodysplastic Syndromes, Multiple Myeloma, Leukemia, Myeloid, Acute, Congenital Abnormalities
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
cyclophosphamideDrug
Also called Cytoxan
60 mg/kg/day intravenous x 2 days pre-transplant, total dose 120 mg/kg
cyclosporineDrug
Also called CSA
Beginning on Day -3 pre-transplant maintaining a level of >200 ng/mL. CSA dosing will be monitored and altered as clinically appropriate by Pharm D or physician, and discontinue at approximately day + 180 post-transplant.
FludarabineDrug
Also called Fludara
25 mg/m2/day intravenous as a 1 hour infusion for consecutive 3 days pre-transplant, total dose 75 mg/m2
Also called MMF
Beginning on day -3, use intravenous route between days -3 and +5, followed by oral administration on Day +6 through +30, if tolerated. 15mg/kg/dose for patients <40 kg, 3 gm/day for patients >40 kg.
total marrow irradiationRadiation
Also called TMI
Dose escalating schedule per Cohort (TMI: 300 cGy) once daily.
umbilical cord blood transplantationProcedure or surgery
Also called umbilical cord blood, allogeneic hematopoietic stem cell transplantation
product will be infused via intravenous drip on Day 0 according to current University of Minnesota guidelines for Umbilical Cord Blood Grafts
Granulocyte colony-stimulating factorBiological
Also called G-CSF
5 mcg/kg/day intravenous or subcutaneous based on body weight beginning on Day +1 after umbilical cord blood infusion until absolute neutrophil count exceeds 2.5 x 10^9/L for 3 consecutive days.
HLA-matched related donor bone marrowBiological
Also called mobilized peripheral blood stem cells
Related donor bone marrow or mobilized stem cells will be collected (target cell dose 5x10^8 nucleated cells/kg recipient weight, minimum 3x10^8 nucleated cells/kg recipient weight) and infused without processing on day 0 according to University of Minnesota Blood and Marrow Transplant Program guidelines.
| Study group | Role | What they receive |
|---|---|---|
| Cohort -1 | Experimental | Patient receives preparative therapy including Fludarabine, cyclophosphamide, and total marrow irradiation of 12 Gy on Days -4 through -1, and starts immunosuppressive therapy using cyclosporine, Mycophenolate Mofetil, followed by umbilical cord blood transplantation, or HLA-matched related donor bone marrow transplantation and granulocyte colony-stimulating factor administration. Receives: Drug: cyclophosphamide; Drug: cyclosporine; Drug: Fludarabine; Drug: mycophenolate mofetil; Radiation: total marrow irradiation; Procedure: umbilical cord blood transplantation; Biological: Granulocyte colony-stimulating factor; Biological: HLA-matched related donor bone marrow |
| Cohort 1 | Experimental | Patient receives preparative therapy including Fludarabine, cyclophosphamide, and total marrow irradiation of 15 Gy on Days -5 through -1, and starts immunosuppressive therapy using cyclosporine, Mycophenolate Mofetil, followed by umbilical cord blood transplantation, or HLA-matched related donor bone marrow transplantation and granulocyte colony-stimulating factor administration. Receives: Drug: cyclophosphamide; Drug: cyclosporine; Drug: Fludarabine; Drug: mycophenolate mofetil; Radiation: total marrow irradiation; Procedure: umbilical cord blood transplantation; Biological: Granulocyte colony-stimulating factor; Biological: HLA-matched related donor bone marrow |
| Cohort 2 | Experimental | Patient receives preparative therapy including Fludarabine, cyclophosphamide, and total marrow irradiation of 18 Gy on Days -6 through -1, and starts immunosuppressive therapy using cyclosporine, Mycophenolate Mofetil, followed by umbilical cord blood transplantation, or HLA-matched related donor bone marrow transplantation and granulocyte colony-stimulating factor administration. Receives: Drug: cyclophosphamide; Drug: cyclosporine; Drug: Fludarabine; Drug: mycophenolate mofetil; Radiation: total marrow irradiation; Procedure: umbilical cord blood transplantation; Biological: Granulocyte colony-stimulating factor; Biological: HLA-matched related donor bone marrow |
| Cohort 3 | Experimental | Patient receives preparative therapy including Fludarabine, cyclophosphamide, and total marrow irradiation of 21 Gy on Days -7 through -1, and starts immunosuppressive therapy using cyclosporine, Mycophenolate Mofetil, followed by umbilical cord blood transplantation, or HLA-matched related donor bone marrow transplantation and granulocyte colony-stimulating factor administration. Receives: Drug: cyclophosphamide; Drug: cyclosporine; Drug: Fludarabine; Drug: mycophenolate mofetil; Radiation: total marrow irradiation; Procedure: umbilical cord blood transplantation; Biological: Granulocyte colony-stimulating factor; Biological: HLA-matched related donor bone marrow |
| Cohort 4 | Experimental | Patient receives preparative therapy including Fludarabine, cyclophosphamide, and total marrow irradiation of 24 Gy on Days -8 through -1, and starts immunosuppressive therapy using cyclosporine, Mycophenolate Mofetil, followed by umbilical cord blood transplantation, or HLA-matched related donor bone marrow transplantation and granulocyte colony-stimulating factor administration. Receives: Drug: cyclophosphamide; Drug: cyclosporine; Drug: Fludarabine; Drug: mycophenolate mofetil; Radiation: total marrow irradiation; Procedure: umbilical cord blood transplantation; Biological: Granulocyte colony-stimulating factor; Biological: HLA-matched related donor bone marrow |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose (MTD) of total marrow irradiation (TMI)
Maximum tolerated dose (MTD) is the highest dose of a drug or treatment that does not cause unacceptable side effects. The MTD of TMI will be determined by using the modified Continual Reassessment Method (CRM). The goal of this CRM will be to identify 1 of the 5 dose levels which corresponds to the desired maximum toxicity rate of <=15%.
Measured: Day 42 and 6 months
Secondary outcomes (10)
Incidence of neutrophil engraftment
Neutrophil engraftment is defined as the first day of three consecutive days where the neutrophil count (absolute neutrophil count) is 500 cells/mm3 (0.5 x 109/L) or greater.
Measured: Day 42
Incidence of platelet engraftment
Platelet engraftment is defined as 20,000/mm^3 (20 x 10^9/L) for 3 consecutive days unsupported by a platelet transfusion.
Measured: 6 Months and 1 Year After Transplantation
Incidence of complete donor chimerism
Defined as a state in bone marrow transplantation in which bone marrow and host cells exist compatibly without signs of graft-versus-host rejection disease.
Measured: Day 100
Incidence of transplantation-related mortality
In the field of transplantation, toxicity is high and all deaths without previous relapse or progression are usually considered as related to transplantation.
Measured: 6 Months
Incidence of grade II-IV and grade III-IV acute graft-versus-host disease (GVHD) after transplantation
Acute Graft-Versus-Host Disease is a severe short-term complication created by infusion of donor cells into a foreign host.
Measured: Day 100
Incidence of chronic GVHD after transplantation
Chronic Graft-Versus-Host Disease is a severe long-term complication created by infusion of donor cells into a foreign host.
Measured: 1 Year
Incidence of relapse after transplantation
The return of disease after its apparent recovery/cessation.
Measured: 1 Year
Disease-free survival after transplantation
Disease-free survival (progression-free survival [PFS]) is the length of time during and after medication or treatment during which the disease being treated (usually cancer) does not get worse. It is sometimes used as a metric to study the health of a person with a disease to try to determine how well a new treatment is working.
Measured: 1 year and 2 years
Durability of remission based on presence of rapid early response after transplantation
Remission - a decrease in or disappearance of signs and symptoms of cancer. In partial remission, some, but not all, signs and symptoms of cancer have disappeared. In complete remission, all signs and symptoms of cancer that can be detected with modern technology have disappeared, although cancer still may be in the body.
Measured: Day 21
Overall survival after transplantation
The percentage of people in a study or treatment group who are alive for a certain period of time after they were diagnosed with or treated for a disease, such as cancer.
Measured: 1 year and 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 May 2008 (estimated)
- Study startAug 2012
- Primary completionNov 2016
- Study completionDec 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Lymphoblastic LeukemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Masonic Cancer Center, University of Minnesota
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- John Wagner, MD, Principal investigator, Masonic Cancer Center, University of Minnesota
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00686556
- Sponsor's protocol ID
- 2007LS024
- Other IDs
- MT2006-24, 0708M14041
- Status last verified
- Dec 2017
- First submitted
- 29 May 2008
- Last updated
- 5 Dec 2017
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 5 Dec 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Total Marrow Irradiation and Myeloablative Chemotherapy Followed By Double Umbilical Cord BloodTransplantation In Patients With Refractory Acute Leukemia
- ClinicalTrials.gov ID
- NCT00686556
- Acronym / sponsor ID
- 2007LS024
- Keywords
- recurrent adult acute lymphoblastic leukemia, recurrent childhood acute lymphoblastic leukemia, recurrent adult acute myeloid leukemia, recurrent childhood acute myeloid leukemia, adult acute myeloid leukemia with 11q23 (MLL) abnormalities, adult acute myeloid leukemia with inv(16)(p13;q22), adult acute myeloid leukemia with t(15;17)(q22;q12), adult acute myeloid leukemia with t(16;16)(p13;q22)
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Masonic Cancer Center, University of MinnesotaUniversity, hospital or other
- Study start
- Aug 2012 (actual)
- Primary completion
- Nov 2016 (actual)
- Study completion
- Dec 2016 (actual)
- First posted
- 30 May 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
RATIONALE: Giving chemotherapy and total marrow irradiation before a donor umbilical cord blood or hematopoietic stem cell transplant helps stop the growth of cancer cells. It may also 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 cyclosporine and mycophenolate mofetil after the transplant may stop this from happening.
PURPOSE: This phase I trial is studying the side effects and best dose of total marrow irradiation when given together with combination chemotherapy and umbilical cord blood hematopoietic stem cell transplant in treating patients with acute leukemia, acute myeloid leukemia or multiple myeloma that did not respond to previous therapy.
Detailed description
OBJECTIVES:
Primary
- Determine the maximum tolerated dose of total marrow irradiation (TMI) delivered by image-guided tomographic intensity-modulated radiotherapy when administered in combination with myeloablative chemotherapy in patients undergoing double umbilical cord blood (UCB) transplantation or hematopoietic stem cell for refractory acute leukemia.
Secondary
- Determine the incidence of engraftment (defined as achievement of neutrophil count > 500/uL at 42 days after transplantation).
- Determine the incidence of platelet engraftment at 6 months and at 1 year after transplantation.
- Evaluate the incidence of complete donor chimerism and the relative contribution of each UCB unit to donor engraftment within the first 100 days after transplantation.
- Determine the incidence of transplantation-related mortality (TRM) at 6 months after treatment with a TMI-containing myeloablative conditioning regimen.
- Determine the incidence of grade II-IV and grade III-IV acute graft-versus-host disease (GVHD) at 100 days after transplantation.
- Determine the incidence of chronic GVHD at 1 year after transplantation.
- Determine the incidence of relapse at 1 year after transplantation.
- Determine the survival and disease-free survival at 1 and 2 years after transplantation.
- Assess the durability of remission based on presence of rapid early response (defined by clearance of leukemic blasts from the bone marrow at 21 days after transplantation).
OUTLINE: This is a dose-escalation study of total marrow irradiation (TMI).
- Myeloablative conditioning regimen: Patients receive fludarabine phosphate IV over 1 hour once daily for 3 days between days -12 and -6 and cyclophosphamide IV once daily for 2 days between days -11 and -6. Patients undergo TMI once daily for 4-8 days between days -8 and -1.
- Donor umbilical cord blood (UCB) transplantation: Patients undergo single-unit or double-unit donor UCB transplantation on day 0. Patients receive filgrastim (G-CSF) IV or subcutaneously once daily beginning on day 1 and continuing until blood counts recover.
- Related Donor: Related donor bone marrow will be collected (target cell dose 5x10^8 nucleated cells/kg recipient weight, minimum 3x10^8 nucleated cells/kg recipient weight) and infused without processing on day 0.
- Graft-versus-host disease (GVHD) prophylaxis: Patients receive cyclosporine IV over 2 hours or orally 2-3 times daily beginning on day -3 and continuing until day 100, followed by a taper until day 180, in the absence of GVHD. Patients also receive mycophenolate mofetil IV or orally 2-3 times daily beginning on day -3 and continuing until day 30 (or 7 days after engraftment), in the absence of acute GVHD.
Patients are followed periodically for up to 2 years after transplantation.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Cohort -1 | Experimental | Drug: cyclophosphamide, Drug: cyclosporine, Drug: Fludarabine, Drug: mycophenolate mofetil, Radiation: total marrow irradiation, Procedure: umbilical cord blood transplantation, Biological: Granulocyte colony-stimulating factor, Biological: HLA-matched related donor bone marrowPatient receives preparative therapy including Fludarabine, cyclophosphamide, and total marrow irradiation of 12 Gy on Days -4 through -1, and starts immunosuppressive therapy using cyclosporine, Mycophenolate Mofetil, followed by umbilical cord blood transplantation, or HLA-matched related donor bone marrow transplantation and granulocyte colony-stimulating factor administration. |
| Cohort 1 | Experimental | Drug: cyclophosphamide, Drug: cyclosporine, Drug: Fludarabine, Drug: mycophenolate mofetil, Radiation: total marrow irradiation, Procedure: umbilical cord blood transplantation, Biological: Granulocyte colony-stimulating factor, Biological: HLA-matched related donor bone marrowPatient receives preparative therapy including Fludarabine, cyclophosphamide, and total marrow irradiation of 15 Gy on Days -5 through -1, and starts immunosuppressive therapy using cyclosporine, Mycophenolate Mofetil, followed by umbilical cord blood transplantation, or HLA-matched related donor bone marrow transplantation and granulocyte colony-stimulating factor administration. |
| Cohort 2 | Experimental | Drug: cyclophosphamide, Drug: cyclosporine, Drug: Fludarabine, Drug: mycophenolate mofetil, Radiation: total marrow irradiation, Procedure: umbilical cord blood transplantation, Biological: Granulocyte colony-stimulating factor, Biological: HLA-matched related donor bone marrowPatient receives preparative therapy including Fludarabine, cyclophosphamide, and total marrow irradiation of 18 Gy on Days -6 through -1, and starts immunosuppressive therapy using cyclosporine, Mycophenolate Mofetil, followed by umbilical cord blood transplantation, or HLA-matched related donor bone marrow transplantation and granulocyte colony-stimulating factor administration. |
| Cohort 3 | Experimental | Drug: cyclophosphamide, Drug: cyclosporine, Drug: Fludarabine, Drug: mycophenolate mofetil, Radiation: total marrow irradiation, Procedure: umbilical cord blood transplantation, Biological: Granulocyte colony-stimulating factor, Biological: HLA-matched related donor bone marrowPatient receives preparative therapy including Fludarabine, cyclophosphamide, and total marrow irradiation of 21 Gy on Days -7 through -1, and starts immunosuppressive therapy using cyclosporine, Mycophenolate Mofetil, followed by umbilical cord blood transplantation, or HLA-matched related donor bone marrow transplantation and granulocyte colony-stimulating factor administration. |
| Cohort 4 | Experimental | Drug: cyclophosphamide, Drug: cyclosporine, Drug: Fludarabine, Drug: mycophenolate mofetil, Radiation: total marrow irradiation, Procedure: umbilical cord blood transplantation, Biological: Granulocyte colony-stimulating factor, Biological: HLA-matched related donor bone marrowPatient receives preparative therapy including Fludarabine, cyclophosphamide, and total marrow irradiation of 24 Gy on Days -8 through -1, and starts immunosuppressive therapy using cyclosporine, Mycophenolate Mofetil, followed by umbilical cord blood transplantation, or HLA-matched related donor bone marrow transplantation and granulocyte colony-stimulating factor administration. |
Who may qualify
- Ages
- Up to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (31 listed)
- Acute lymphoblastic leukemia
- Myelodysplastic syndrome
- Acute myeloid leukemia
- Multiple myeloma
- Other high risk hematologic malignancies - to be approved by 2 or more hematology/oncology and BMT physicians
Key exclusion criteria (5 listed)
- Active uncontrolled infection at time of enrollment or documented fungal infection within 3 months.
- Evidence of Human immunodeficiency virus (HIV) infection
- Pregnant or breast feeding. The agents used in this study may be teratogenic to a fetus and there is no information on the excretion of agents into breast milk. All females of childbearing potential must have a blood test or urine study within 2 weeks prior to registration to rule out pregnancy.
- Prior myeloablative transplant within the last 6 months
- Prior total body irradiation (TBI) making total marrow irradiation (TMI) not feasible
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| cyclophosphamideAlso: Cytoxan60 mg/kg/day intravenous x 2 days pre-transplant, total dose 120 mg/kg | Drug | Cohort -1, Cohort 1, Cohort 2, Cohort 3, Cohort 4 |
| cyclosporineAlso: CSABeginning on Day -3 pre-transplant maintaining a level of >200 ng/mL. CSA dosing will be monitored and altered as clinically appropriate by Pharm D or physician, and discontinue at approximately day + 180 post-transplant. | Drug | Cohort -1, Cohort 1, Cohort 2, Cohort 3, Cohort 4 |
| FludarabineAlso: Fludara25 mg/m2/day intravenous as a 1 hour infusion for consecutive 3 days pre-transplant, total dose 75 mg/m2 | Drug | Cohort -1, Cohort 1, Cohort 2, Cohort 3, Cohort 4 |
| mycophenolate mofetilAlso: MMFBeginning on day -3, use intravenous route between days -3 and +5, followed by oral administration on Day +6 through +30, if tolerated. 15mg/kg/dose for patients <40 kg, 3 gm/day for patients >40 kg. | Drug | Cohort -1, Cohort 1, Cohort 2, Cohort 3, Cohort 4 |
| total marrow irradiationAlso: TMIDose escalating schedule per Cohort (TMI: 300 cGy) once daily. | Radiation | Cohort -1, Cohort 1, Cohort 2, Cohort 3, Cohort 4 |
| umbilical cord blood transplantationAlso: umbilical cord blood, allogeneic hematopoietic stem cell transplantationproduct will be infused via intravenous drip on Day 0 according to current University of Minnesota guidelines for Umbilical Cord Blood Grafts | Procedure or surgery | Cohort -1, Cohort 1, Cohort 2, Cohort 3, Cohort 4 |
| Granulocyte colony-stimulating factorAlso: G-CSF5 mcg/kg/day intravenous or subcutaneous based on body weight beginning on Day +1 after umbilical cord blood infusion until absolute neutrophil count exceeds 2.5 x 10^9/L for 3 consecutive days. | Biological | Cohort -1, Cohort 1, Cohort 2, Cohort 3, Cohort 4 |
| HLA-matched related donor bone marrowAlso: mobilized peripheral blood stem cellsRelated donor bone marrow or mobilized stem cells will be collected (target cell dose 5x10^8 nucleated cells/kg recipient weight, minimum 3x10^8 nucleated cells/kg recipient weight) and infused without processing on day 0 according to University of Minnesota Blood and Marrow Transplant Program guidelines. | Biological | Cohort -1, Cohort 1, Cohort 2, Cohort 3, Cohort 4 |
Primary outcome
Maximum tolerated dose (MTD) of total marrow irradiation (TMI)
Time frame: Day 42 and 6 months
Maximum tolerated dose (MTD) is the highest dose of a drug or treatment that does not cause unacceptable side effects. The MTD of TMI will be determined by using the modified Continual Reassessment Method (CRM). The goal of this CRM will be to identify 1 of the 5 dose levels which corresponds to the desired maximum toxicity rate of <=15%.
10 secondary outcomes
Incidence of neutrophil engraftment
Time frame: Day 42
Incidence of platelet engraftment
Time frame: 6 Months and 1 Year After Transplantation
Incidence of complete donor chimerism
Time frame: Day 100
Incidence of transplantation-related mortality
Time frame: 6 Months
Incidence of grade II-IV and grade III-IV acute graft-versus-host disease (GVHD) after transplantation
Time frame: Day 100
Incidence of chronic GVHD after transplantation
Time frame: 1 Year
Incidence of relapse after transplantation
Time frame: 1 Year
Disease-free survival after transplantation
Time frame: 1 year and 2 years
Durability of remission based on presence of rapid early response after transplantation
Time frame: Day 21
Overall survival after transplantation
Time frame: 1 year and 2 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Dec 2017.
Related trials for Acute Lymphoblastic Leukemia
RecruitingPhase 2/3
A Clinical Trial of MK-1045 in People With B-cell Acute Lymphoblastic Leukemia (MK-1045-005)
B-cell Acute Lymphoblastic Leukemia
RecruitingPhase 1
225Ac-DOTA-Anti-CD38 Daratumumab Monoclonal Antibody With Fludarabine, Melphalan and Total Marrow and Lymphoid Irradiation as Conditioning Treatment for Donor Stem Cell Transplant in Patients With High-Risk Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia and Myelodysplastic Syndrome
Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia
Recruiting
More Than Just X-Rays - Imaging of Chemotherapy-induced Morphological and Functional Cardiovascular and Lung Changes After Childhood ALL and Other Cancers - a Monocentric Late Effects Study (MaximALL)
Acute Lymphatic Leukemia, Lymphoma
RecruitingPhase 1/2
Phase I/II Trial: Engineered Donor Graft (Orca Q) for Pediatric Hematopoietic Cell Transplant (HCT)
Acute Myeloid Leukemia, Acute Lymphoid Leukemia
RecruitingPhase 1/2
A Clinical Study of MK-1045 (CN201) in People With Precursor B-cell Acute Lymphoblastic Leukemia (MK-1045-002)
Acute Lymphoblastic Leukemia
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
John Wagner, MD principal investigator
Masonic Cancer Center, University of Minnesota
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing cyclophosphamide, cyclosporine and Fludarabine in people with Acute Lymphoblastic Leukemia and Myelodysplastic Syndrome, run by Masonic Cancer Center, University of Minnesota at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 31 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Dec 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum tolerated dose (MTD) of total marrow irradiation (TMI) (time frame: Day 42 and 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Dec 2017.