Chemotherapy, Total-Body Irradiation, and Umbilical Cord Blood Transplant in Treating Patients With High-Risk Hematological Cancer - Full Text View

Sponsors and Collaborators:	Vanderbilt-Ingram Cancer Center National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00608517

Purpose

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: This phase I trial is studying the side effects and best way to give chemotherapy together with total-body irradiation and umbilical cord blood transplant in treating patients with high-risk hematological cancer.

Condition	Intervention	Phase
Graft Versus Host Disease Leukemia Lymphoma Multiple Myeloma and Plasma Cell Neoplasm Myelodysplastic Syndromes Myelodysplastic/Myeloproliferative Diseases	Drug: anti-thymocyte globulin Drug: cyclophosphamide Drug: fludarabine phosphate Drug: methylprednisolone Procedure: total-body irradiation	Phase I

Genetics Home Reference related topics: aceruloplasminemia hemophilia

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

Drug Information available for: Cyclophosphamide Methylprednisolone Fludarabine Fludarabine monophosphate Tacrolimus Mycophenolate Mofetil Mycophenolate mofetil hydrochloride Tacrolimus anhydrous

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Open Label
Official Title:	The Treatment of Hematologic Malignancies With Single or Double Umbilical Cord Blood Unit Transplantation Followed by Graft-Versus-Host Prophylaxis With Tacrolimus and Mycophenolate Mofetil

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Non-relapse mortality at 100 days [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Sustained donor engraftment [ Designated as safety issue: No ]
Neutrophil and platelet recovery [ Designated as safety issue: Yes ]
Incidence and severity of acute graft-versus-host disease (GVHD) and chronic GVHD [ Designated as safety issue: Yes ]
Relapse rate [ Designated as safety issue: No ]
All-cause mortality at 100 days [ Designated as safety issue: Yes ]
Immune reconstitution [ Designated as safety issue: No ]
Overall survival [ Designated as safety issue: No ]

Estimated Enrollment:	49
Study Start Date:	September 2005
Estimated Primary Completion Date:	September 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Myeloablative conditioning (pediatric patients): Experimental 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.	Drug: anti-thymocyte globulin Given IV Drug: cyclophosphamide Given IV Drug: methylprednisolone Given IV Procedure: total-body irradiation Given daily for 1-4 days
Myeloablative conditioning (adults 18-40 years old): Experimental 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.	Drug: cyclophosphamide Given IV Drug: fludarabine phosphate Given IV Procedure: total-body irradiation Given daily for 1-4 days
Reduced-intensity conditioning: Experimental 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.	Drug: cyclophosphamide Given IV Drug: fludarabine phosphate Given IV Procedure: total-body irradiation Given daily for 1-4 days

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-verus-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 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 GVHD prophylaxis comprising tacrolimus and 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 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.

Eligibility

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

Criteria

DISEASE CHARACTERISTICS:

Diagnosis of 1 of the following:
- Acute leukemia in a remission (less than 5% leukemic marrow blasts) at time of study entry
  - Acute leukemia (lymphocytic, myeloid, undifferentiated, or biphenotypic) in complete remission (CR) 2 or beyond
  - Acute lymphocytic leukemia, Philadelphia chromosome positive disease in CR1 or beyond
  - Acute myeloid leukemia in CR1 if evolved from a myeloproliferative disorder or myelodysplastic syndromes (MDS)
  - Acute leukemia in CR1 if there is a failure to recover normal blood counts or the development of MDS after induction chemotherapy
  - Therapy-related acute leukemia in CR1 or beyond
- Chronic myelogenous leukemia (CML)
  - Chronic phase-1 (imatinib mesylate failure or imatinib mesylate intolerance) or any CML beyond first chronic phase
- Chronic lymphocytic leukemia
  - Must have failed two lines of conventional therapy but still chemosensitive to third-line therapy
- Myelodysplastic syndromes (IPSS intermediate-1 risk or higher)
  - Therapy-related MDS (irrespective of IPSS) eligible
- Multiple myeloma
  - Must have had prior chemotherapy or autologous transplant
- Chemosensitive non-Hodgkin lymphoma or Hodgkin lymphoma
  - In CR or partial response after failing induction therapy
- High-risk acute leukemia/lymphoma (e.g., Nk/T cell, human T-cell lymphotrophic virus [HTLV]-associated leukemia/lymphoma, or other T-cell lymphoma/leukemia) in first best response
No available HLA-identical or 1 antigen/allele-mismatched (Class I-A, B, or Class II DR locus)-related donor
Umbilical cord blood must be at least a HLA 4/6 match (Class I-A, B by low resolution, or Class II-DR by high resolution) to recipient
- For double umbilical cord stem cell transplantation, each unit should be at least a 4/6 match (Class I-A or B by low resolution or Class II-DR by high resolution) to recipient, and should be at least a 4/6 match (Class I-A, B by low resolution or Class II-DR by high resolution) to each other

PATIENT CHARACTERISTICS:

Inclusion criteria:

Karnofsky performance status (PS) 70-100% (adult patients) OR Lansky PS 70-100% (pediatric patients)
Creatinine clearance > 60 mL/min
Left ventricular ejection fraction > 50%
DLCO, FEV_1, and FVC > 60% (for patients > 6 years of age)
Total bilirubin < 3 times upper limit of normal (ULN)
AST < 3 times ULN
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception

Exclusion criteria:

HIV positive
Organ dysfunction
Active use of illicit drugs as evidenced by a positive toxicology screen for a substance not prescribed by a medical professional
Actively smoking as evidenced by a positive nicotine screen just prior to initiating the preparative regimen
Any other unrelated malignancy within the past 5 years* except for the following:
- Skin cancer (squamous cell or basal cell)
- Cervical dysplasia (cervical intraepithelial neoplasm I-III)
- Any other malignancy currently in remission and treated with curative intent NOTE: *For patients with secondary MDS or secondary acute leukemia, the previous nonhematopoietic neoplasm should be in remission but can be within 5 years of study entry

PRIOR CONCURRENT THERAPY:

See Disease Characteristics

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00608517

Locations

United States, Tennessee
Vanderbilt-Ingram Cancer Center - Cool Springs
Nashville, Tennessee, United States
Vanderbilt-Ingram Cancer Center at Franklin
Nashville, Tennessee, United States
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, United States, 37232-6838
Veterans Affairs Medical Center - Nashville
Nashville, Tennessee, United States, 37212

Sponsors and Collaborators

Vanderbilt-Ingram Cancer Center

National Cancer Institute (NCI)

Investigators

Study Chair:

Brian Engelhardt, MD

Vanderbilt-Ingram Cancer Center

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Study ID Numbers:	CDR0000581386, VU-VICC-BMT-0552
Study First Received:	January 31, 2008
Last Updated:	November 16, 2008
ClinicalTrials.gov Identifier:	NCT00608517
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

graft versus host disease
accelerated phase chronic myelogenous leukemia
adult acute lymphoblastic leukemia in remission
adult acute myeloid leukemia in remission
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)
blastic phase chronic myelogenous leukemia
childhood acute lymphoblastic leukemia in remission
childhood acute myeloid leukemia in remission
childhood chronic myelogenous leukemia
chronic phase chronic myelogenous leukemia
de novo myelodysplastic syndromes

extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
myelodysplastic/myeloproliferative disease, unclassifiable
nodal marginal zone B-cell lymphoma
noncontiguous stage II adult Burkitt lymphoma
noncontiguous stage II adult diffuse large cell lymphoma
noncontiguous stage II adult diffuse mixed cell lymphoma
noncontiguous stage II adult diffuse small cleaved cell lymphoma
noncontiguous stage II adult immunoblastic large cell lymphoma
noncontiguous stage II adult lymphoblastic lymphoma
noncontiguous stage II adult non-Hodgkin lymphoma
noncontiguous stage II grade 1 follicular lymphoma
noncontiguous stage II grade 2 follicular lymphoma
noncontiguous stage II grade 3 follicular lymphoma
noncontiguous stage II mantle cell lymphoma
noncontiguous stage II marginal zone lymphoma

Study placed in the following topic categories:

Philadelphia Chromosome
Blast Crisis
Chronic myelogenous leukemia
Methylprednisolone
Graft versus host disease
Hodgkin lymphoma, adult
Lymphoma, Mantle-Cell
Lymphoma, small cleaved-cell, diffuse
Tacrolimus
Lymphoma, large-cell, immunoblastic
Preleukemia
Hemorrhagic Disorders
Multiple myeloma
Leukemia, Lymphocytic, Chronic, B-Cell
Mycophenolate mofetil

Neoplasm Metastasis
Acute myeloid leukemia, adult
Hodgkin Disease
Methylprednisolone Hemisuccinate
Chronic lymphocytic leukemia
Myelodysplastic syndromes
Lymphoma, Large B-Cell, Diffuse
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Immunoproliferative Disorders
Hematologic Diseases
Leukemia, B-cell, chronic
Blood Coagulation Disorders
Acute myelogenous leukemia
Myeloproliferative Disorders
Leukemia, Myeloid

Additional relevant MeSH terms:

Antimetabolites
Anti-Inflammatory Agents
Antimetabolites, Antineoplastic
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Antiemetics
Hormones
Neuroprotective Agents
Pathologic Processes
Therapeutic Uses
Syndrome
Cardiovascular Diseases

Alkylating Agents
Disease
Neoplasms by Histologic Type
Antineoplastic Agents, Hormonal
Immune System Diseases
Gastrointestinal Agents
Glucocorticoids
Protective Agents
Immunosuppressive Agents
Pharmacologic Actions
Neoplasms
Autonomic Agents
Myeloablative Agonists
Antineoplastic Agents, Alkylating
Peripheral Nervous System Agents

ClinicalTrials.gov processed this record on January 16, 2009