AlloHCT From Matched Unrelated Donors in Pts w/ Advanced Hematologic Malignancies & Disorders

NCT00547196 | Completed Results DMC

• 4 other identifiers: 02165P30CA033572CHNMC-02165CDR0000570249
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 2

Brief Summary

RATIONALE: Giving chemotherapy with or without total-body irradiation before a donor umbilical cord blood transplant helps stop the growth of cancer or abnormal cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. When the 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 cyclosporine and mycophenolate mofetil before and after transplant may stop this from happening. PURPOSE: This clinical trial is studying how well four different chemotherapy regimens given with or without total-body irradiation before umbilical cord blood transplant work in treating patients with relapsed or refractory hematologic cancer.

Conditions

Leukemia; Lymphoma; Myelodysplastic Syndromes

Keywords

refractory chronic lymphocytic leukemia; adult acute myeloid leukemia in remission; recurrent adult acute myeloid leukemia; 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); adult acute lymphoblastic leukemia in remission; accelerated phase chronic myelogenous leukemia; blastic phase chronic myelogenous leukemia; chronic phase chronic myelogenous leukemia; de novo myelodysplastic syndromes; previously treated myelodysplastic syndromes; secondary myelodysplastic syndromes; recurrent adult Burkitt lymphoma; recurrent adult diffuse large cell lymphoma; recurrent adult diffuse mixed cell lymphoma; recurrent adult diffuse small cleaved cell lymphoma; recurrent adult grade III lymphomatoid granulomatosis; recurrent adult immunoblastic large cell lymphoma; recurrent adult lymphoblastic lymphoma; recurrent grade 1 follicular lymphoma; recurrent grade 2 follicular lymphoma; recurrent grade 3 follicular lymphoma; recurrent mantle cell lymphoma; recurrent marginal zone lymphoma; recurrent small lymphocytic lymphoma; extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue; nodal marginal zone B-cell lymphoma; splenic marginal zone lymphoma; relapsing chronic myelogenous leukemia; recurrent cutaneous T-cell non-Hodgkin lymphoma; secondary acute myeloid leukemia

Outcome Measures

Primary Outcomes (1)

• Survival Rate at Day 100 After Allogeneic Transplant From Umbilical Cord Blood (UCB)

  Number of surviving patients at Day 100 post-transplant divided by number of patients undergone transplantation.

  From transplant to Day 100 post-transplant

Secondary Outcomes (1)

• Survival Rate at Day 180 After Allogeneic Transplant From Umbilical Cord Blood (UCB)

  From transplant up to Day 180 post-transplant

Study Arms (4)

Regimen I (FTBI, Cyclophosphamide, Fludarabine)

EXPERIMENTAL

Patients undergo FTBI 2-3 times a day on days -9 to -6 for a total of 11 fractions. Patients also receive cyclophosphamide IV over 2 hours on days -5 and -4 and fludarabine phosphate IV on days -5 to -2. UCB transplantation: Patients receive 2 combined units of UCB IV on day 0. Patients also receive G-CSF IV or subcutaneously beginning on day 5 (or later) and continuing until blood counts recover. GVHD prophylaxis: Patients receive cyclosporine IV twice daily beginning on day -1 followed by a taper according to institutional guidelines. Patients also receive mycophenolate mofetil orally or IV beginning on day 0 and continuing until day 27 (or as clinically indicated).

Biological: filgrastim; Drug: Cyclophosphamide; Drug: Cyclosporine; Drug: Fludarabine phosphate; Drug: Mycophenolate Mofetil; Procedure: allogeneic hematopoietic stem cell transplantation; Procedure: umbilical cord blood transplantation; Radiation: Fractionated total body irradiation

Regimen II (Busulfan, Fludarabine, Melphalan)

EXPERIMENTAL

Patients receive a test dose of busulfan on day -10 and then dose adjusted busulfan IV 3-4 times daily on days -9 to -6, melphalan IV on days -5 and -4, and fludarabine phosphate IV on days -5 to -2. UCB transplantation: Patients receive 2 combined units of UCB IV on day 0. Patients also receive G-CSF IV or subcutaneously beginning on day 5 (or later) and continuing until blood counts recover. GVHD prophylaxis: Patients receive cyclosporine IV twice daily beginning on day -1 followed by a taper according to institutional guidelines. Patients also receive mycophenolate mofetil orally or IV beginning on day 0 and continuing until day 27 (or as clinically indicated).

Biological: filgrastim; Drug: Busulfan; Drug: Cyclosporine; Drug: Fludarabine phosphate; Drug: Melphalan; Drug: Mycophenolate Mofetil; Procedure: allogeneic hematopoietic stem cell transplantation; Procedure: umbilical cord blood transplantation

Regimen III (TBI, Cyclophosphamide, Fludarabine)

EXPERIMENTAL

Patients receive fludarabine phosphate IV on days -8 to -4 and cyclophosphamide IV over 2 hours on day -3 and undergo TBI (single dose) on day -2. UCB transplantation: Patients receive 2 combined units of UCB IV on day 0. Patients also receive G-CSF IV or subcutaneously beginning on day 5 (or later) and continuing until blood counts recover. GVHD prophylaxis: Patients receive cyclosporine IV twice daily beginning on day -1 followed by a taper according to institutional guidelines. Patients also receive mycophenolate mofetil orally or IV beginning on day 0 and continuing until day 27 (or as clinically indicated).

Biological: filgrastim; Drug: Cyclophosphamide; Drug: Cyclosporine; Drug: Fludarabine phosphate; Drug: Mycophenolate Mofetil; Procedure: allogeneic hematopoietic stem cell transplantation; Procedure: umbilical cord blood transplantation; Radiation: total-body irradiation

Regimen IV (Fludarabine, Melphalan)

EXPERIMENTAL

Patients receive fludarabine phosphate IV on days -7 to -3 and melphalan IV on day -2. UCB transplantation: Patients receive 2 combined units of UCB IV on day 0. Patients also receive G-CSF IV or subcutaneously beginning on day 5 (or later) and continuing until blood counts recover. GVHD prophylaxis: Patients receive cyclosporine IV twice daily beginning on day -1 followed by a taper according to institutional guidelines. Patients also receive mycophenolate mofetil orally or IV beginning on day 0 and continuing until day 27 (or as clinically indicated).

Biological: filgrastim; Drug: Cyclosporine; Drug: Fludarabine phosphate; Drug: Melphalan; Drug: Mycophenolate Mofetil; Procedure: allogeneic hematopoietic stem cell transplantation; Procedure: umbilical cord blood transplantation

Interventions

filgrastim BIOLOGICAL

Regimen I (FTBI, Cyclophosphamide, Fludarabine); Regimen II (Busulfan, Fludarabine, Melphalan); Regimen III (TBI, Cyclophosphamide, Fludarabine); Regimen IV (Fludarabine, Melphalan)

Busulfan DRUG

Also known as: Busilvex

Regimen II (Busulfan, Fludarabine, Melphalan)

Cyclophosphamide DRUG

Also known as: CTX

Regimen I (FTBI, Cyclophosphamide, Fludarabine); Regimen III (TBI, Cyclophosphamide, Fludarabine)

Cyclosporine DRUG

Also known as: CsA

Regimen I (FTBI, Cyclophosphamide, Fludarabine); Regimen II (Busulfan, Fludarabine, Melphalan); Regimen III (TBI, Cyclophosphamide, Fludarabine); Regimen IV (Fludarabine, Melphalan)

Fludarabine phosphate DRUG

Also known as: Fludara

Regimen I (FTBI, Cyclophosphamide, Fludarabine); Regimen II (Busulfan, Fludarabine, Melphalan); Regimen III (TBI, Cyclophosphamide, Fludarabine); Regimen IV (Fludarabine, Melphalan)

Melphalan DRUG

Also known as: Alkeran

Regimen II (Busulfan, Fludarabine, Melphalan); Regimen IV (Fludarabine, Melphalan)

Mycophenolate Mofetil DRUG

Also known as: MMF

Regimen I (FTBI, Cyclophosphamide, Fludarabine); Regimen II (Busulfan, Fludarabine, Melphalan); Regimen III (TBI, Cyclophosphamide, Fludarabine); Regimen IV (Fludarabine, Melphalan)

allogeneic hematopoietic stem cell transplantation PROCEDURE

Also known as: AlloHCT

Regimen I (FTBI, Cyclophosphamide, Fludarabine); Regimen II (Busulfan, Fludarabine, Melphalan); Regimen III (TBI, Cyclophosphamide, Fludarabine); Regimen IV (Fludarabine, Melphalan)

umbilical cord blood transplantation PROCEDURE

Regimen I (FTBI, Cyclophosphamide, Fludarabine); Regimen II (Busulfan, Fludarabine, Melphalan); Regimen III (TBI, Cyclophosphamide, Fludarabine); Regimen IV (Fludarabine, Melphalan)

total-body irradiation RADIATION

Also known as: TBI

Regimen III (TBI, Cyclophosphamide, Fludarabine)

Fractionated total body irradiation RADIATION

Also known as: FTBI

Regimen I (FTBI, Cyclophosphamide, Fludarabine)

Eligibility Criteria

• Age: 0 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: * Histologically confirmed hematological or lymphatic malignancy, including any of the following: * Acute myeloid leukemia * Relapsed or primary refractory disease with \< 10% blasts on peripheral blood smear * In first remission with poor risk factors and molecular prognosis \[i.e., AML with -5, -7, t(6;9), tri8, -11\] (preparative regimen 3 or 4) * Acute lymphocytic leukemia * In second complete remission or higher OR in first remission with poor risk factors, including any of the following (preparative regimen 1 or 2): * BCR/ABL by fluorescence in situ hybridization (FISH) or reverse transcriptase-polymerase chain reaction * t(9;22)(q34;q11) detected by cytogenetics * Chromosomes \< 44 by cytogenetics * DNA index \< 0.81 by flow cytometry * Any rearrangement of chromosome 11 that results in disruption of MLL gene (11q23) by cytogenetics and SER * In first remission with poor risk factors and molecular prognosis \[ALL with Philadelphia chromosome-positive t(9;22), t(4;22), (q34;q11)\] (preparative regimen 3 or 4) * Chronic myelogenous leukemia * In accelerated phase or greater (preparative regimen 1 or 2) * In accelerated or second chronic phase (preparative regimen 3 or 4) * Myelodysplastic syndromes * With deletion of chromosome 7 or short arm of chromosome 5 (preparative regimen 1 or 2) * In high and high-intermediate risk categories (preparative regimen 3 or 4) * Non-Hodgkin lymphoma in relapse with marrow involvement * Refractory chronic lymphocytic leukemia * Patients deemed ineligible for conventional high-dose chemotherapy programs (i.e., regimens 1 or 2) due to any of the following concurrent medical conditions may be eligible for regimens 3 or 4 at the discretion of the treating physician and principal investigator (preparative regimen 3 or 4): * LVEF \< 50% and \> 40% * FEV1, FVC, or DLCO \< 50% * Bilirubin \> 3 mg/dL * Creatinine \> 2 mg/dL * Two partially HLA-matched umbilical cord blood (UCB) units available * HLA-matched minimally at 4 of 6 HLA-A, HLA-B, and -DRB1 loci with the patient * DRB1 matched by high resolution DNA typing * HLA-A and HLA-B matched by low resolution at the "serological match" level * Two pooled units with a nucleated cell number \> 2.5 x 10\^7/kg * No available HLA-identical sibling or 1 antigen-mismatched related donor * No available HLA-matched unrelated bone marrow donor PATIENT CHARACTERISTICS: * See Disease Characteristics * Karnofsky performance status (PS) 60-100% OR Lansky PS 60-100% OR Zubrod PS 0-1 * Physiological age 60 or less (at any chronological age) * Weight \> 50 kg * Creatinine normal for age OR creatinine clearance by 24-hour urine collection or glomerular filtration rate \> 60 mL/min * Bilirubin ≤ 1.5 mg/dL * LVEF ≥ 50% * DLCO ≥ 60% of predicted * No HIV-1 infection * No active uncontrolled infection * Not pregnant * Negative pregnancy test * Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: * Recovered from prior intensive chemotherapy

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (2)

Banner Good Samaritan Medical Center

Phoenix, Arizona, 85006, United States

Location

City of Hope Medical Center

Duarte, California, 91010-3000, United States

Location

MeSH Terms

Conditions

Leukemia; Lymphoma; Myelodysplastic Syndromes; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Myeloid, Acute; Congenital Abnormalities; Leukemia, Myeloid, Accelerated Phase; Blast Crisis; Leukemia, Myeloid, Chronic-Phase; Burkitt Lymphoma; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Lymphoma, Large-Cell, Immunoblastic; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Lymphoma, Follicular; Lymphoma, Mantle-Cell; Lymphoma, B-Cell, Marginal Zone; Lymphoma, T-Cell, Cutaneous

Interventions

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

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Bone Marrow Diseases; Leukemia, B-Cell; Leukemia, Lymphoid; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Leukemia, Myeloid; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Myeloproliferative Disorders; Cell Transformation, Neoplastic; Carcinogenesis; Neoplastic Processes; Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Lymphoma, B-Cell; Lymphoma, T-Cell

Intervention Hierarchy (Ancestors)

Granulocyte Colony-Stimulating Factor; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative; Radiotherapy; Investigative Techniques

Results Point of Contact

• Title: Dr. Anna Pawlowska, MD
• Organization: City of Hope

apawlowska@coh.org

626-359-8111

Study Officials

• Anna Pawlowska, MD

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 19, 2007
• First Posted: October 22, 2007
• Study Start: August 16, 2005
• Primary Completion: November 11, 2009
• Study Completion: May 28, 2024
• Last Updated: June 14, 2024
• Results First Posted: April 13, 2023

Record last verified: 2024-06

Locations

US (2)