Donor Umbilical Cord Blood Transplant in Treating Patients With Hematologic Cancer

NCT00723099 | Completed Phase 2 Results DMC

• 4 other identifiers: 2239.00NCI-2009-015512239P30CA015704
• Study Type: interventional
• Target: 73
• Locations: 1 country
• Sites: 6

Brief Summary

This phase II trial is studying how well umbilical cord blood transplant from a donor works in treating patients with hematological cancer. Giving chemotherapy and total-body irradiation (TBI) 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 an unrelated donor, that do not exactly match the patient's blood, 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 (called graft-versus-host disease). Giving cyclosporine and mycophenolate mofetil before and after transplant may stop this from happening.

Conditions

Acute Lymphoblastic Leukemia; Acute Myeloid Leukemia; Aggressive Non-Hodgkin Lymphoma; Chronic Myelogenous Leukemia; Chronic Phase Chronic Myelogenous Leukemia; Indolent Non-Hodgkin Lymphoma; Lymphoma; Mixed Phenotype Acute Leukemia; Myelodysplastic Syndrome; Myeloproliferative Neoplasm; Recurrent Chronic Lymphocytic Leukemia; Recurrent Follicular Lymphoma; Recurrent Lymphoplasmacytic Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Plasma Cell Myeloma; Recurrent Small Lymphocytic Lymphoma; Recurrent T-Cell Non-Hodgkin Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Chronic Myelogenous Leukemia; Refractory Follicular Lymphoma; Refractory Hodgkin Lymphoma; Refractory Lymphoplasmacytic Lymphoma; Refractory Mantle Cell Lymphoma; Refractory Small Lymphocytic Lymphoma; T-Cell Non-Hodgkin Lymphoma

Outcome Measures

Primary Outcomes (1)

• Overall Survival

  Kaplan-Meier and cumulative incidence estimates will be used.

  At 1 year

Secondary Outcomes (8)

• Median Time to ANC > 500

  By day 55

• Number of Participants With Graft Failure/Rejection

  By day 55

• Time to Platelet Engraftment of > 20,000 Cells Per mm3

  By 6 months

• Percent of Patients With Grade II-IV Acute Graft Versus Host Disease

  By day 100

• Percent of Patients With Acute GVHD Grades III-IV

  100 days

Study Arms (1)

Treatment (chemotherapy, transplant)

EXPERIMENTAL

CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV over 1 hour on days -6 to -2 and cyclophosphamide IV over 1-2 hours on day -6. Patients undergo a lower dose of TBI on day -1. UMBILICAL CORD BLOOD TRANSPLANT: Patients undergo donor umbilical cord blood infusion on day 0. IMMUNOSUPRESSIVE THERAPIES: Patients receive cyclosporine IV over 1 hour every 8-12 hours on days 0 to +180 and mycophenolate mofetil IV or PO every 8 hours on days -3 to +96.

Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Drug: Cyclophosphamide; Drug: Cyclosporine; Drug: Fludarabine Phosphate; Other: Laboratory Biomarker Analysis; Drug: Mycophenolate Mofetil; Radiation: Total-Body Irradiation; Procedure: Umbilical Cord Blood Transplantation

Interventions

Allogeneic Hematopoietic Stem Cell Transplantation PROCEDURE

Undergo umbilical cord blood transplant

Also known as: Allogeneic Hematopoietic Cell Transplantation, Allogeneic Stem Cell Transplantation, HSC, HSCT

Treatment (chemotherapy, transplant)

Cyclophosphamide DRUG

Given IV

Also known as: (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, CP monohydrate, CTX, CYCLO-cell, Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR- 138719

Treatment (chemotherapy, transplant)

Cyclosporine DRUG

Given IV

Also known as: 27-400, Ciclosporin, CsA, Cyclosporin, Cyclosporin A, Gengraf, Neoral, OL 27-400, Sandimmun, Sandimmune, SangCya

Treatment (chemotherapy, transplant)

Fludarabine Phosphate DRUG

Given IV

Also known as: 2-F-ara-AMP, 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-, Beneflur, Fludara, SH T 586

Treatment (chemotherapy, transplant)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (chemotherapy, transplant)

Mycophenolate Mofetil DRUG

Given IV or PO

Also known as: Cellcept, MMF

Treatment (chemotherapy, transplant)

Total-Body Irradiation RADIATION

Undergo TBI

Also known as: Total Body Irradiation, Whole-Body Irradiation

Treatment (chemotherapy, transplant)

Umbilical Cord Blood Transplantation PROCEDURE

Undergo umbilical cord blood transplant

Also known as: Cord Blood Transplantation, UCB transplantation

Treatment (chemotherapy, transplant)

Eligibility Criteria

• Age: Up to 69 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients \> 70 may be considered if performance status \> 80% or Eastern Cooperative Oncology Group (ECOG) =\< 1 and comorbidity score \< 3; these patients must be discussed with the principal investigator (PI), Rachel Salit prior to enrollment
• Adequate cardiac function defined as absence of decompensated congestive heart failure, or uncontrolled arrhythmia and:
• Left ventricular ejection fraction \>= 35% or
• Fractional shortening \> 22%
• Adequate pulmonary function defined as diffusion capacity of carbon monoxide (DLCO) \> 30% predicted, and absence of oxygen (O2) requirements
• Adequate hepatic function; patients with clinical or laboratory evidence of liver disease will be evaluated for the cause of liver disease, its clinical severity in terms of liver function, histology, and the degree of portal hypertension; patients with fulminant liver failure, cirrhosis with evidence of portal hypertension or bridging fibrosis, alcoholic hepatitis, esophageal varices, a history of bleeding esophageal varices, hepatic encephalopathy, or correctable hepatic synthetic dysfunction evidenced by prolongation of the prothrombin time, ascites related to portal hypertension, bacterial or fungal abscess, biliary obstruction, chronic viral hepatitis with total serum bilirubin \> 3 mg/dL, and symptomatic biliary disease will be excluded
• Adequate renal function defined as creatinine =\< 2.0 mg/dl (adults) or creatinine clearance \> 40 ml/min (pediatrics)
• All adults with a creatinine \> 1.2 or a history of renal dysfunction must have estimated creatinine clearance \> 40 ml/min
• Performance status score: Karnofsky (for adults) \>= 60 or ECOG 0-2; Lansky (for children) score \>= 50
• If recent mold infection, e.g., Aspergillus, must be cleared by infectious disease
• Second hematopoietic cell transplant: Must be \>= 3 months after prior myeloablative transplant
• Patients who have received \< 2 cycles of multiagent chemotherapy and patients who have received no multiagent chemotherapy within the 3 months previous to umbilical cord blood transplant (UCBT) as well as patients experiencing graft failure following previous allogeneic transplant
• Acute myeloid leukemia/acute lymphoblastic leukemia, including biphenotypic acute leukemia or mixed-lineage leukemia: Must have \< 5% morphologic marrow blasts in an evaluable marrow (\> 25% of normal cellularity for age) collected less than one month prior to start of conditioning; patients persistently aplastic for greater than one month since completing last chemotherapy are also eligible with the approval of the PI or designee
• Chronic myelogenous leukemia: All types, except refractory blast crisis; chronic phase patients must have failed or been intolerant to Gleevec or other tyrosine kinase inhibitors; at time of transplant, patients must have \< 5% blasts in an evaluable marrow (\> 25% of normal cellularity for age) by morphology within the bone marrow
• Myelodysplastic syndrome (MDS): Any subtype; morphologic blasts must be less than 5% in an evaluable marrow (\> 25% of normal cellularity for age); if blasts are 5% or more, patient requires induction chemotherapy pre-transplant to reduce blast count to less than 5%; patients who have a hypocellular marrow in the absence of excess blasts that is related to the underlying disease or as a result of treatment for MDS may also be eligible with the approval of the PI or designee

You may not qualify if:

• Patients with an available 5-6/6 HLA-A, B, DRB1 matched sibling donor
• Pregnancy or breastfeeding
• Evidence of human immunodeficiency virus (HIV) infection or known HIV positive serology
• Uncontrolled viral or bacterial infection at the time of study enrollment
• Active or recent (prior 6 month) invasive fungal infection without infectious disease (ID) consult and approval
• Active central nervous system malignancy
• Patients who have received \>= 2 cycles of multiagent chemotherapy within the 3 months previous to UCBT; patients who have had previous autologous transplant within 12 months of UCBT are excluded regardless of history of recent treatment
• DONOR: Any cord blood units with \< 1.5 x 10\^7 total nucleated cells per kilogram recipient weight
• DONOR: Any cord blood units without the full maternal testing and negative results for hepatitis A, B, C, HIV, and human T-lymphotropic virus (HTLV-1) viruses; any additional available virology results on the unit itself will be reviewed but are not mandated, complete or always available; cord blood units are presumed to be cytomegalovirus (CMV) negative regardless of serologic testing due to passive transmission of maternal CMV antibodies

Sponsors & Collaborators

• Fred Hutchinson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (6)

University of Colorado Hospital

Aurora, Colorado, 80045, United States

Location

Colorado Blood Cancer Institute

Denver, Colorado, 80218, United States

Location

LDS Hospital

Salt Lake City, Utah, 84143, United States

Location

VA Puget Sound Health Care System

Seattle, Washington, 98101, United States

Location

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

Froedtert and the Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myeloid, Acute; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Chronic-Phase; Lymphoma; Leukemia, Biphenotypic, Acute; Myelodysplastic Syndromes; Myeloproliferative Disorders; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Follicular; Lymphoma, B-Cell, Marginal Zone; Lymphoma, Mantle-Cell; Multiple Myeloma; Lymphoma, T-Cell; Hodgkin Disease

Interventions

Cyclophosphamide; Cyclosporine; Cyclosporins; fludarabine phosphate; Mycophenolic Acid; Whole-Body Irradiation; Cord Blood Stem Cell Transplantation

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Myeloid; Bone Marrow Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Leukemia, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids; Radiotherapy; Therapeutics; Investigative Techniques; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Transplantation; Surgical Procedures, Operative

Limitations and Caveats

Patients were given 200 or 300 cGy TBI based on set definitions of high risk or low risk of graft failure. This was NOT a randomized study designed to show which dose of TBI was more effective.

Results Point of Contact

• Title: Rachel Salit
• Organization: Fred Hutchinson Cancer Research Center

rsalit@fredhutch.org

206-667-1317

Study Officials

• Rachel Salit

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 25, 2008
• First Posted: July 28, 2008
• Study Start: June 25, 2008
• Primary Completion: July 31, 2018
• Study Completion: July 31, 2018
• Last Updated: December 27, 2019
• Results First Posted: October 11, 2019

Record last verified: 2019-12

Locations

US (6)