A Myeloablative Conditioning Regimen and Total Body Irradiation Followed by the Transplantation for Patients With Hematological Malignancy - Full Text View

Sponsored by:	Memorial Sloan-Kettering Cancer Center
Information provided by:	Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:	NCT00597519

Purpose

In this study two cord blood collections will be used to increase the number of cord blood cells you will receive on transplant day. We call this a "double unit" cord blood transplant. A previous study suggests double unit cord blood transplant may have a better result. The main purpose of this study is to find out how good a cord blood transplant using two cord blood collections from two different babies is at curing you of your cancer. Double unit cord blood transplants are now being studied as a way to increase the number of cord blood cells given to bigger children and adult patients.

Based on studies that have already been done double unit cord blood transplant appears to be safer than if only one cord blood unit is used. However, double unit cord blood transplant is a fairly new form of treatment.

Condition	Intervention	Phase
Cancer Leukemia Myelodysplastic Syndrome Non-Hodgkin's Lymphoma	Drug: Fludarabine, Cyclophosphamide Procedure: Transplantation	Phase II

MedlinePlus related topics: Cancer Leukemia, Adult Acute Leukemia, Adult Chronic Leukemia, Childhood Lymphoma

Drug Information available for: Cyclophosphamide Fludarabine Fludarabine monophosphate Cyclosporin Cyclosporine Granulocyte colony-stimulating factor Mycophenolate Mofetil Mycophenolate mofetil hydrochloride Diphenhydramine Diphenhydramine citrate Diphenhydramine hydrochloride Promethazine Promethazine hydrochloride Acetaminophen Hydroxyzine Hydroxyzine dihydrochloride Hydroxyzine pamoate

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Open Label, Single Group Assignment, Safety/Efficacy Study
Official Title:	A Myeloablative Conditioning Regimen Consisting of Cyclophosphamide, Fludarabine and Total Body Irradiation Followed by the Transplantation of Unrelated Donor Double Unit Umbilical Cord Blood Grafts for Patients With Hematological Malignancy.

Further study details as provided by Memorial Sloan-Kettering Cancer Center:

Primary Outcome Measures:

To obtain a preliminary estimate of efficacy of double unit UCBT as measured by overall and disease-free survival at 1 year. [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

The incidence and rate of donor derived neutrophil and platelet recovery; the contribution of each unit to initial and sustained engraftment; the incidence and severity of acute GVHD at 100 days [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	30
Study Start Date:	March 2006
Estimated Study Completion Date:	March 2010
Estimated Primary Completion Date:	March 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Treatment: Experimental Patients with hematopoietic malignancy at high-risk for relapse or with advanced disease will receive myeloablative conditioning with cyclophosphamide (Cy), low dose fludarabine (Flu) and total body irradiation (TBI) with post transplantation cyclosporine (CSA) and mycophenolate mofetil (MMF) for GVHD prophylaxis.	Drug: Fludarabine, Cyclophosphamide Fludarabine 25 mg/m2/day IV in the morning x 3 days (days -7, -6 and -5) for a total dose of 75 mg/m2 followed by Cyclophosphamide on days -6 and -5. 60mg/kg/day IV over 30-60 minutes x 2 days (days -6 and -5). High volume fluids should commence approximately 12 hours prior to drug and continue until 24 hours after second dose. Total Body Irradiation: 125 cGy x 11 doses (TID on days -3, -2, -1 and BID on day 0) for a total TBI dose of 1375 cGy. All patients will receive GVHD prophylaxis with 2 drugs: Cyclosporine A and Mycophenolate mofetil (MMF). Units should be given consecutively each over approximately 10-30 minutes.Pre-medication should include acetaminophen and diphenhydramine or hydroxyzine.G-CSF 5 mcg/kg/day IV/SQ (dose rounded to vial size to a maximum of 480 mcg) will be given from day +1 until ANC ≥ 2500/uL x 2 days. Procedure: Transplantation The UCB ( Umbilical Cord Blood) collection known as a unit is processed to remove excess plasma and red cells, tested for sterility, HLA-typed, cryopreserved and stored. This protocol involves the administration of two UCB units from two different donors. The units will be thawed in the Cytotherapy Laboratory as per the current standard operating procedure.

Arms

Assigned Interventions

Treatment: Experimental

Patients with hematopoietic malignancy at high-risk for relapse or with advanced disease will receive myeloablative conditioning with cyclophosphamide (Cy), low dose fludarabine (Flu) and total body irradiation (TBI) with post transplantation cyclosporine (CSA) and mycophenolate mofetil (MMF) for GVHD prophylaxis.

Drug: Fludarabine, Cyclophosphamide

Fludarabine 25 mg/m2/day IV in the morning x 3 days (days -7, -6 and -5) for a total dose of 75 mg/m2 followed by Cyclophosphamide on days -6 and -5. 60mg/kg/day IV over 30-60 minutes x 2 days (days -6 and -5). High volume fluids should commence approximately 12 hours prior to drug and continue until 24 hours after second dose.

Total Body Irradiation: 125 cGy x 11 doses (TID on days -3, -2, -1 and BID on day 0) for a total TBI dose of 1375 cGy. All patients will receive GVHD prophylaxis with 2 drugs: Cyclosporine A and Mycophenolate mofetil (MMF).

Units should be given consecutively each over approximately 10-30 minutes.Pre-medication should include acetaminophen and diphenhydramine or hydroxyzine.G-CSF 5 mcg/kg/day IV/SQ (dose rounded to vial size to a maximum of 480 mcg) will be given from day +1 until ANC ≥ 2500/uL x 2 days.

Procedure: Transplantation

The UCB ( Umbilical Cord Blood) collection known as a unit is processed to remove excess plasma and red cells, tested for sterility, HLA-typed, cryopreserved and stored. This protocol involves the administration of two UCB units from two different donors. The units will be thawed in the Cytotherapy Laboratory as per the current standard operating procedure.

Detailed Description:

This is a single arm phase 2 study to obtain a preliminary estimate of efficacy of myeloablative double unit umbilical cord blood transplantation (UCBT) as measured by overall and disease-free survival at 1 year post transplantation. The UCB graft will consist of two (or double) units from two unrelated newborn donors. Patients with hematopoietic malignancy at high-risk for relapse or with advanced disease will receive myeloablative conditioning with cyclophosphamide (Cy),low dose fludarabine (Flu) and total body irradiation (TBI) with post transplantation cyclosporine (CSA) and mycophenolate mofetil (MMF) for GVHD prophylaxis.

Eligibility

Ages Eligible for Study:	4 Years to 50 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Age 4 - 50 years
Patient should not have a related or unrelated volunteer donor that is suitably HLA matched and available in the required time period or be a suitable candidate for an autologous stem cell transplant.
Patients will have one of the following hematological malignancies: Acute myelogenous leukemia (AML); Acute lymphoblastic leukemia (ALL)
Acute undifferentiated leukemia (AUL), infant leukemia, or biphenotypic leukemia in CR1, CR2 or CR3. Patients with infant leukemia must be eligible to receive total body irradiation.
Juvenile Myelomonocytic leukemia (JMML) with < 30% bone marrow blasts.
Chronic myelogenous leukemia (CML)
Myelodysplastic Syndrome (MDS)
Non-Hodgkin's Lymphoma
Patients with adequate organ function and performance status
Double Unit Umbilical Cord Blood Grafts

Exclusion Criteria:

available in the required time period.
Patient is a candidate for an autologous stem cell transplant.
Active CNS leukemia.
Acute Myelogenous Leukemia in greater than CR2.
Acute Myelogenous Leukemia evolved from myelofibrosis.
Acute Lymphoblastic Leukemia, acute undifferentiated leukemia, biphenotypic leukemia or infant leukemia greater than CR3.
Any acute leukemia
Bone Marrow aplasia (defined as BM cellularity less than 5% at transplant work-up)
or MDS with greater than 10% bone marrow blasts refractory to chemotherapy
CML in blast crisis
NHL refractory to chemotherapy (less than PR after 2 or more regimens)
Prior autologous or allogeneic HSC transplant at any time
Prior radiation therapy rendering patient ineligible for TBI
Uncontrolled viral, bacteria or fungal infection at time of study enrollment;
Seropositive or NAT positive for HIV
Females who are pregnant or breast feeding
Patient or guardian unable to give informed consent or unable to comply with the treatment protocol including appropriate supportive care, follow-up, and research tests.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00597519

Contacts

Contact: Juliet Barker, MBBS

barkerj@mskcc.org

Locations

United States, New York
Memorial Sloan-Kettering Cancer Center	Recruiting
New York, New York, United States, 10065
Contact: Juliet Barker, MBBS barkerj@mskcc.org

Sponsors and Collaborators

Memorial Sloan-Kettering Cancer Center

Investigators

Principal Investigator:

Juliet Barker, MBBS

Memorial Sloan-Kettering Cancer Center

More Information

Memorial Sloan-Kettering web site This link exits the ClinicalTrials.gov site

Responsible Party:	Memorial Sloan-Kettering Cancer Center ( Juliet Barker, MBBS )
Study ID Numbers:	06-014, CA23766
Study First Received:	December 26, 2007
Last Updated:	September 5, 2008
ClinicalTrials.gov Identifier:	NCT00597519
Health Authority:	United States: Institutional Review Board

Keywords provided by Memorial Sloan-Kettering Cancer Center:

Cancer
Leukemia
Myelodysplastic Syndrome

Non-Hodgkin's Lymphoma
Total Body Irradiation
Umbilical Cord Blood Grafts

Study placed in the following topic categories:

Cyclosporine
Precancerous Conditions
Hematologic Neoplasms
Lymphoma, small cleaved-cell, diffuse
Cyclophosphamide
Cyclosporins
Leukemia
Preleukemia
Promethazine
Mycophenolate mofetil
Lymphoma
Acetaminophen
Myelodysplastic syndromes

Immunoproliferative Disorders
Hematologic Diseases
Myelodysplastic Syndromes
Myelodysplasia
Fludarabine monophosphate
Lymphatic Diseases
Hydroxyzine
Fludarabine
Bone Marrow Diseases
Lymphoproliferative Disorders
Lymphoma, Non-Hodgkin
Diphenhydramine

Additional relevant MeSH terms:

Antimetabolites
Antimetabolites, Antineoplastic
Neoplasms by Histologic Type
Disease
Molecular Mechanisms of Pharmacological Action
Immune System Diseases
Immunologic Factors
Antineoplastic Agents
Physiological Effects of Drugs
Immunosuppressive Agents

Pharmacologic Actions
Neoplasms
Pathologic Processes
Neoplasms by Site
Syndrome
Therapeutic Uses
Myeloablative Agonists
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Alkylating Agents

ClinicalTrials.gov processed this record on January 16, 2009