Treatment of Single or Double Umbilical Cord Trans + Graft-versus-host Disease (GVHD) Prophylaxis w/ Tacrolimus & Mycophenolate Mofetil

NCT ID: NCT00608517

Last Updated: 2014-05-20

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: NA
• Total Enrollment: 6 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-09-30
• Study Completion Date: 2011-05-31

Brief Summary

RATIONALE: Giving chemotherapy and total-body irradiation before a donor umbilical cord blood transplant helps stop the growth of cancer and abnormal cells and helps 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 tacrolimus and mycophenolate mofetil before and after transplant may stop this from happening.

PURPOSE: To look at the ability of umbilical cord blood cells from one or two unrelated donors to serve as a source of stem cells for people needing a bone marrow transplant.

Detailed Description

OBJECTIVES:

Primary

• To determine the safety (as assessed by the day 100 non-relapse mortality) and feasibility of single or double umbilical cord stem cell transplantation in patients with hematological malignancies receiving graft-versus-host disease (GVHD) prophylaxis comprising tacrolimus and mycophenolate mofetil (MMF).

Secondary

• To assess sustained donor engraftment, neutrophil recovery, platelet recovery, incidence and severity of acute graft-versus-host disease (GVHD) and chronic GVHD, relapse rate, 100-day all-cause mortality, overall survival, and immune reconstitution after single or double umbilical cord stem cell transplantation in patients with hematologic malignancies receiving graft-versus-host disease(GVHD) prophylaxis comprising tacrolimus and mycophenolate mofetil (MMF).

OUTLINE:

• Conditioning: Patients receive myeloablative or reduced-intensity conditioning regimen according to age and prior treatment.

• Myeloablative conditioning (pediatric patients): Patients undergo total-body irradiation on days -7 to -4, and receive cyclophosphamide IV over 1 hour on days -3 and -2, methylprednisolone IV twice daily on days -3 to -1, and anti-thymocyte globulin IV over 4 hours on days -3 to -1.
• Myeloablative conditioning (adult patients 18-40 years old): Patients receive fludarabine phosphate IV over 30 minutes on days -6 to -4, cyclophosphamide IV over 1 hour on days -5 and -4, and undergo total-body irradiation on days -3 to -1.
• Reduced-intensity conditioning (patients over 40 and no more than 50 years old OR deemed ineligible for above myeloablative conditioning regimen due to previous treatment): Patients receive fludarabine phosphate IV over 30 minutes on days -6 to -2 and cyclophosphamide IV over 1 hour on day -6 and undergo total-body irradiation on day -1.
• Umbilical cord blood transplantation (UCBT): All patients undergo single- or double-unit umbilical cord blood transplantation (UCBT)on day 0.
• Graft-versus-host disease prophylaxis: Patients receive tacrolimus IV continuously or orally twice daily on days -2 to 180 followed by a tapering and mycophenolate mofetil IV or orally twice daily on days 0-100 followed by a tapering over the next 3 months. Patients also receive filgrastim (G-CSF) IV or subcutaneously beginning on day 0* and continuing until blood counts recover.

NOTE: *In adult patients receiving a reduced intensity transplant, G-CSF will be started when the total white cell count falls below 2.5 x 109/L.

After completion of study treatment, patients are followed monthly for 1 year and then every 2-4 months thereafter.

Conditions

Graft Versus Host Disease; Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Pediatric Myeloablative conditioning

Patients undergo total-body irradiation on days -7 to -4, and receive cyclophosphamide IV over 1 hour on days -3 and -2, methylprednisolone IV twice daily on days -3 to -1, and anti-thymocyte globulin IV over 4 hours on days -3 to -1.

Group Type: EXPERIMENTAL

anti-thymocyte globulin

Intervention Type: BIOLOGICAL

Given IV

cyclophosphamide

Intervention Type: DRUG

Given IV

methylprednisolone

Intervention Type: DRUG

Given IV

total-body irradiation

Intervention Type: RADIATION

Given daily for 1-4 days

Adult Myeloablative conditioning

Patients receive fludarabine phosphate IV over 30 minutes on days -6 to -4, cyclophosphamide IV over 1 hour on days -5 and -4, and undergo total-body irradiation on days -3 to -1.

Group Type: EXPERIMENTAL

cyclophosphamide

Intervention Type: DRUG

Given IV

fludarabine phosphate

Intervention Type: DRUG

Given IV

total-body irradiation

Intervention Type: RADIATION

Given daily for 1-4 days

Reduced-intensity conditioning

Patients receive fludarabine phosphate IV over 30 minutes on days -6 to -2 and cyclophosphamide IV over 1 hour on day -6 and undergo total-body irradiation on day -1.

Group Type: EXPERIMENTAL

cyclophosphamide

Intervention Type: DRUG

Given IV

fludarabine phosphate

Intervention Type: DRUG

Given IV

total-body irradiation

Intervention Type: RADIATION

Given daily for 1-4 days

Interventions

anti-thymocyte globulin

Given IV

Intervention Type: BIOLOGICAL

cyclophosphamide

Given IV

Intervention Type: DRUG

fludarabine phosphate

Given IV

Intervention Type: DRUG

methylprednisolone

Given IV

Intervention Type: DRUG

total-body irradiation

Given daily for 1-4 days

Intervention Type: RADIATION

Other Intervention Names

ATG; Cytoxin; Fludara; Medrol

Eligibility Criteria

Inclusion Criteria

Only one of the following should be present:

• Acute leukemia (lymphocytic or myeloid or undifferentiated or biphenotypic) in complete remission 2 or beyond
• Acute lymphocytic leukemia, Philadelphia chromosome positive in complete remission 1 or beyond
• Acute myeloid leukemia in complete remission 1 if it has evolved from a myeloproliferative disorder (MPD) or myelodysplastic syndrome (MDS).
• Acute leukemia in complete remission 1 if there is a failure to recover normal blood counts or the development of MDS following induction chemotherapy.
• Therapy related acute leukemia in complete remission 1 or beyond
• Chronic myeloid leukemia (CML) chronic phase-1 (imatinib failures, imatinib intolerance), or any CML beyond first chronic phase
• Myelodysplastic syndromes (Intermediate -1 or higher risk by IPSS)
• Therapy related MDS (irrespective of IPSS)
• Multiple myeloma must have had prior chemotherapy or autologous transplant
• Chronic lymphocytic leukemia must have failed two lines of conventional therapy but still chemosensitive to third line therapy.
• Chemosensitive Non-Hodgkin's lymphoma or Hodgkin's lymphoma in CR or PR after failing induction therapy.
• High risk acute leukemia/lymphoma eg Nk/T cell, HTLV associated leukemia/lymphoma, other T cell lymphoma/leukemia in first best response
• For patients with acute leukemia-they must be in a remission (less than 5% leukemic marrow blasts) at time of study entry.

• Karnofsky score of > 70%
• Estimated creatinine clearance of > 60 ml/min
• Left ventricular ejection fraction of >50%
• Pulmonary function test with DLCO, FEV1 and FVC of >60%
• Total bilirubin and SGOT of < 3.0 x upper limits of normal
• Note: Age 18- 40 years for adult myeloablative conditioning Age > 40 -50 years for adult reduced intensity conditioning

• Karnofsky or Lansky score of > 70%
• Estimated Creatinine clearance of > 60 ml/min
• Left ventricular ejection fraction of >50%
• Pulmonary function test with FEV1 and FVC of >60% (for patients >6 years of age)
• Total bilirubin and SGOT of < 3.0 x upper limits of normal
• Note: All pediatric patients will receive myeloablative conditioning

• No available HLA identical or 1 antigen/allele mismatched (Class I-A, B or Class II DR locus) related donor

• At least a HLA 4/6 match (Class I-A, B by low resolution, Class II-DR by high resolution) to recipient
• For double UCB SCT each unit should be at least a 4/6 match (Class I-A,B by low resolution, Class II-DR by high resolution) to recipient, and should be at least a 4/6 match (Class I-A,B by low resolution, Class II-DR by high resolution) to each other

• For Single UCB SCT: the unit will have ≥ 3.5 X 107 NC/kg of recipient body weight (For pediatric patients a cell dose ≥ 3.0 X 107 NC/kg of recipient body weight is acceptable). Recipient body weight will be determined as per standard guidelines.
• For Double UCB SCT: (done only if no single UCB unit ≥ 3.5 X 107 NC/kg of recipient body weight is available for adults, and ≥ 3.0 X 107 NC/kg of recipient body weight is available for pediatric patients )
• The larger of the two units (UCB1) will have a minimum cell dose of 2.0 X 107 NC/kg of recipient body weight. The smaller of the two units (UCB2) will have a minimum of 0.5 X 107 NC/kg of recipient body weight.

The total cell dose UCB1 + UCB2 will be ≥ 2.5 X 107 NC/kg of recipient body weight.

-Adult patients eligible for a double UCB SCT but without an appropriate second UCB unit will be enrolled in the study if their single UCB unit contains ≥ 2.5 x 107 NC/kg recipient body weight.

Exclusion Criteria

• Organ dysfunction as per standard guidelines. Unable to give informed consent (for adults only)
• Pregnant or lactating
• Sexually active individuals capable of becoming pregnant or causing a pregnancy who are unable or unwilling to use appropriate contraceptives.
• Active use of illicit drugs as evidenced by a positive toxicology screen for a substance not prescribed by a medical professional just prior to initiating the preparative regimen
• Actively smoking as evidenced by a positive nicotine screen just prior to initiating the preparative regimen
• HIV positive
• Patients with other unrelated malignancies will be excluded except:
• diagnosis of skin cancer (squamous cell or basal cell)
• diagnosis of cervical dysplasia (CIN I-III)
• any other malignancy which is currently in remission and was treated with curative intent more than 5 years preceding study entry
• In patients with secondary MDS or secondary acute leukemias-the previous non-hematopoietic neoplasm should be in remission but can be within 5 years of study entry

• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Vanderbilt-Ingram Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Brian Engelhardt, MD

Assistant Professor of Medicine; Hematologist/Oncologist

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Brian Engelhardt, MD

Role: STUDY_CHAIR

Vanderbilt-Ingram Cancer Center

Locations

Vanderbilt-Ingram Cancer Center - Cool Springs

Nashville, Tennessee, United States

Vanderbilt-Ingram Cancer Center at Franklin

Nashville, Tennessee, United States

Veterans Affairs Medical Center - Nashville

Nashville, Tennessee, United States

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, United States

Countries

United States

Other Identifiers

VU-VICC-BMT-0552

Identifier Type: -

Identifier Source: secondary_id

VICC BMT 0552

Identifier Type: -

Identifier Source: org_study_id

NCT00244036

Identifier Type: -

Identifier Source: nct_alias