Conditioning Regimen and the Transplantation of Unrelated Donor Umbilical Cord Blood in Patients With Hematologic Malignancies.

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by Memorial Sloan-Kettering Cancer Center
Sponsor:
Information provided by (Responsible Party):
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT00739141
First received: August 19, 2008
Last updated: April 9, 2014
Last verified: April 2014
  Purpose

The traditional way of doing a donor transplant is to give high doses of chemotherapy and radiation before giving the stem cells. However, high doses of chemotherapy and radiation can have serious side-effects. The doctors think that the transplant will be safer and more likely to be successful with reduced doses of chemotherapy and radiation. The purpose of this study is to find out how good a combination of chemotherapy and radiation at reduced doses followed by a cord blood transplant are at treating cancer.

The stem cells chosen for the transplant are from umbilical cord blood. Umbilical cord blood is collected from healthy newborn babies and frozen. One cord blood collection is called a "cord blood unit." On transplant day, the cord blood will be given through the catheter just like a blood transfusion. Transplants done this way have been successful. However, this type of transplant is fairly new. Therefore, it is important to study it so the doctors can better understand how it works.

Most blood or bone marrow transplants using donor stem cells are done as part of a study. When patients are on a study we test new ways of treating them which we think may be better than the old ways. We collect information about the result of this treatment so we can understand how well the treatment works. This is so we can learn better ways to treat our patients.


Condition Intervention Phase
Leukemia
Myelodysplastic Syndrome
Non-Hodgkins Lymphoma
Chronic Myelogenous Leukemia
Other: fludarabine, cyclophosphamide, thiotepa, radiation therapy, unrelated donor umbilical cord blood graft
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Reduced Intensity Conditioning Regimen and the Transplantation of Unrelated Donor Umbilical Cord Blood in Patients With Hematologic Malignancies.

Resource links provided by NLM:


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

Primary Outcome Measures:
  • To obtain a preliminary estimate of disease-free survival at 1 year post UCBT. [ Time Frame: conclusion of study ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • The speed of neutrophil and platelet recovery post allograft [ Time Frame: conclusion of study ] [ Designated as safety issue: No ]
  • The incidence and speed of donor-derived engraftment and contribution of each UCB unit to engraftment. [ Time Frame: conclusion of study ] [ Designated as safety issue: No ]

Estimated Enrollment: 55
Study Start Date: August 2008
Estimated Study Completion Date: August 2015
Estimated Primary Completion Date: August 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
There are three chemotherapy drugs involved. They are called fludarabine (5 doses), cyclophosphamide (1 dose), and thiotepa (2 doses). Also two days of radiation therapy. This is called Total Body Irradiation or TBI. The TBI if given for two days before, the transplant. On transplant day, the cord blood cells will be given through a catheter. The immune suppressing drugs given are called cyclosporine-A (CSA) and mycophenolate mofetil (MMF). These will be started 3 days before the transplant and will be given through the catheter. Later they can be given as tablets.
Other: fludarabine, cyclophosphamide, thiotepa, radiation therapy, unrelated donor umbilical cord blood graft
Cyclophosphamide 50 mg/kg/dose x 1 IV day -6 (1 dose) Fludarabine 30 mg/m2/dose x 5 IV days -6 to -2 (5 doses) Thiotepa 5 mg/kg/dose x 2 IV days -5 to -4 (2 doses) TBI 200 cGy/dose x 2 days -2 to -1 (2 doses). On transplant day, the cord blood cells will be given through your catheter. The immune suppressing drugs you will receive are called cyclosporine-A (CSA) and mycophenolate mofetil (MMF). These will be started 3 days before the transplant and will be given through your catheter. Later they can be given as tablets.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • At least one cycle of induction or re-induction chemotherapy or lymphoma chemotherapy or azacitidine or decitabine or tyrosine kinase inhibitor.
  • Patients aged 18-70 years at initial referral with no available and suitably matched related or unrelated donor.
  • Acute myelogenous leukemia (AML):
  • Complete first remission (CR1) at high risk for relapse as defined by:
  • Known prior diagnosis of myelodysplasia (MDS) or myeloproliferative disorder;
  • Therapy related AML;
  • White cell count at presentation > 100,000;
  • Presence of extramedullary leukemia at diagnosis;
  • Any unfavorable sub type by FAB or WHO classification;
  • High-risk cytogenetics (eg those associated with MDS, abnormalities of 5, 7, 8, Philadelphia chromosome, complex karyotype)or high risk molecular abnormalities;
  • Requirement for 2 or more inductions to achieve CR1.
  • Any patient with newly diagnosed AML with intermediate risk cytogenetics.
  • Any patient unable to tolerate consolidation chemotherapy as would have been deemed appropriate by the treating physician.
  • Complete second remission (CR2).
  • Other acute leukemias that are ambiguous lineage or of other types eg blastic plasmacytoid dendritic cell neoplasm in CR1 or CR2
  • Acute lymphoblastic leukemia (ALL):
  • lymphoblastic leukemia (ALL):
  • Complete first remission (CR1) at high risk for relapse as defined by:
  • White cell count at presentation > 30,000 for B-cell lineage and >100,000 for Tcell lineage;
  • Presence of a high-risk cytogenetic abnormality such as t(9;22), t(1;19), t(4;11) or other MLL rearrangements (11q23)or other high-risk molecular abnormality;
  • Failure to achieve complete remission after four weeks of induction therapy;
  • Any patient with newly diagnosed ALL > or = to 50 years-old;
  • Any patient unable to tolerate consolidation and/or maintenance chemotherapy as would have been deemed appropriate by the treating physician.
  • Complete second remission (CR2).
  • Myelodysplastic Syndrome (MDS):
  • Intermediate-1 International Prognostic Scoring System (IPSS) score with poor risk cytogenetics as defined by IPSS.
  • Intermediate- 2 or High International Prognostic Scoring System (IPSS) score.
  • MDS/ myeloproliferative disorder overlap syndromes.
  • Any score with life threatening cytopenia(s), including red cell or platelet transfusion dependence.
  • Receipt of at least one cycle of cytotoxic chemotherapy, azacitidine or decitabine.
  • MDS patients must have < or = to 5% bone marrow myeloblasts and ANC > or = to 0.5 (growth factor supported if necessary) at transplant work-up.
  • Chronic myelogenous leukemia (CML) patients who have failed or are intolerant of tyrosine kinase inhibitors.
  • Any Non-Hodgkins lymphoma (including chronic lymphocytic leukemia) at high-risk of relapse not suitable for either high dose myeloablative conditioning or non-myeloablative conditioning
  • Eligible patients with DLC NHL will:

have relapsed disease following initial therapy but failed to mobilize or had bone marrow involvement and therefore are not suitable for an autologous transplant OR

  • have failed an autologous transplant and be in CR after salvage chemotherapy.
  • Eligible patients with transformed indolent NHL/CLL will:

have CR/PR of the large cell component of their disease after either salvage chemotherapy or an autologous transplant.

  • Eligible patients with mantle cell NHL will:

be high-risk as such as p53 positivity and be in 1st CR/PR after initial therapy OR have relapsed disease following initial therapy and be in 2nd or 3rd CR/PR after salvage chemotherapy.

  • Eligible patients with indolent B cell NHL (such as, but not limited to, follicular, small cell or marginal zone NHL) or CLL will have 2nd or subsequent progression (pre-allograft cytoreduction necessary but CR/PR not required).
  • Timing of UCBT:
  • Admission for UCBT must be within an acceptable time period after the pre-allograft chemotherapy. This will be defined as within 100 days of the start day of the last cycle of chemotherapy (or decitabine or azacitidine) or other disease active agent).
  • Organ Function and Performance Status Criteria:
  • Karnofsky score > or = to 70 %.
  • calculated creatinine clearance > or = to 60 ml/min
  • bilirubin < than or = to 1.5 mg/dL, ALT < than or = to 3 x upper limit of normal unless benign congenital hyperbilirubinemia,
  • pulmonary function (spirometry and corrected DLCO) > or = to 50% normal.
  • left ventricular ejection fraction > or = to 50%.
  • albumin > or = to 3.0.
  • Graft Criteria:
  • 2 UCB units selected according to current MSKCC unit selection algorithm. HLA testing to be done using molecular techniques: A and B antigen to at least intermediate resolution and DRB1 allele at high-level resolution.
  • Each unit will be at least 4/6 HLA-A, B antigen and DRB1 allele matched with the recipient.
  • In addition, each unit will have a cryopreserved dose of at least 2.0 x 10^7 total nucleated cells/recipient body weight (TNC/kg).
  • Units with attached segments for confirmatory typing will be given preference.

Exclusion Criteria:

  • Diagnosis: acute leukemia in morphologic relapse or with morphologic persistent disease (cytogenetic or molecular persistence/relapse in morphologic CR are eligible); MDS or CML or other myeloproliferative disorder with > 5% blasts.
  • Prior allogeneic transplant.
  • Active and uncontrolled infection at time of transplantation.
  • HIV infection.
  • Inadequate performance status/ organ function.
  • Pregnancy 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00739141

Contacts
Contact: Juliet Barker, MBBS 212-639-3468
Contact: Hugo Castro-Malaspina, MD 212-639-8197

Locations
United States, New York
Memorial Sloan-Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Juliet Barker, MBBS    212-639-3468      
Contact: Hugo Castro-Malaspina, MD    212-639-8197      
Principal Investigator: Juliet Barker, MBBS         
Sponsors and Collaborators
Memorial Sloan-Kettering Cancer Center
Investigators
Principal Investigator: Juliet Barker, MBBS Memorial Sloan-Kettering Cancer Center
  More Information

Additional Information:
No publications provided by Memorial Sloan-Kettering Cancer Center

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT00739141     History of Changes
Other Study ID Numbers: 08-087
Study First Received: August 19, 2008
Last Updated: April 9, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Memorial Sloan-Kettering Cancer Center:
CYCLOPHOSPHAMIDE (CYTOXAN)
CYCLOSPORINE A
FLUDARABINE
G-CSF
MYCOPHENOLATE MOFETIL (MMF)
THI0TEPA
UMBILICAL CORD BLOOD (UCB)
08-087

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Lymphoma
Lymphoma, Non-Hodgkin
Myelodysplastic Syndromes
Preleukemia
Hematologic Neoplasms
Neoplasms by Histologic Type
Neoplasms
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Precancerous Conditions
Neoplasms by Site
Cyclophosphamide
Cyclosporins
Cyclosporine
Mycophenolate mofetil
Thiotepa
Fludarabine phosphate
Fludarabine
Mycophenolic Acid
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 28, 2014