Umbilical Cord Blood (UCB) Transplant, Fludarabine, Melphalan, and Anti-thymocyte Globulin (ATG) in Treating Patients With Hematologic Cancer

NCT00827099 | Terminated Phase 2 Results

• 2 other identifiers: CDR0000632453BMTGG-NSH-801
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

RATIONALE: Giving low doses of chemotherapy before a donor umbilical cord blood transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving tacrolimus and mycophenolate mofetil after the transplant may stop this from happening. PURPOSE: This phase II trial is studying how well giving umbilical cord blood transplant together with fludarabine, melphalan, and antithymocyte globulin works in treating patients with hematologic cancer.

Conditions

Myeloproliferative Disorders; Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes

Keywords

accelerated phase cml; adult ALL in remission; adult AML in remission; adult AML with 11q23 (MLL) abnormalities; adult AML 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; chronic myelomonocytic leukemia; chronic phase chronic myelogenous leukemia; prolymphocytic leukemia; recurrent adult T-cell leukemia/lymphoma; relapsing chronic myelogenous leukemia; secondary acute myeloid leukemia; refractory chronic lymphocytic leukemia; stage I chronic lymphocytic leukemia; stage II chronic lymphocytic leukemia; stage III chronic lymphocytic leukemia; stage IV chronic lymphocytic leukemia; recurrent adult Hodgkin lymphoma; anaplastic large cell lymphoma; angioimmunoblastic T-cell lymphoma; cutaneous B-cell non-Hodgkin lymphoma; recurrent cutaneous T-cell non-Hodgkin lymphoma; recurrent mycosis fungoides/Sezary syndrome; adult grade III lymphomatoid granulomatosis; adult nasal type extranodal NK/T-cell lymphoma; Waldenstrom macroglobulinemia; extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue; nodal marginal zone B-cell lymphoma; splenic marginal zone 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 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; chronic idiopathic myelofibrosis; stage I multiple myeloma; stage II multiple myeloma; stage III multiple myeloma; refractory multiple myeloma; de novo myelodysplastic syndromes; previously treated myelodysplastic syndromes; secondary myelodysplastic syndromes

Outcome Measures

Primary Outcomes (1)

• Number of Participants With 100 Day Transplant-related Mortality (TRM)

  100 Day TRM is death within 100 days from transplant related complications

  100 days

Secondary Outcomes (5)

• Number of Patients That Engrafted Blood Counts by 30 Days After Transplant

  Day 30

• Percentage of Donor and Host Chimerism of Each Cord Blood Unit

  day 30, day 60, day 90

• Number of Patients Who Experience Acute and Chronic Graft-vs-host Disease After Transplant.

  Day 30

• Number of Patients Who Experience Disease Relapse Post-transplant

  Day 100, 6 months, 1 year, 18 months, 24 months

• Number of Patients Who Survive Following Treatment on This Protocol

  Through Death

Interventions

anti-thymocyte globulin BIOLOGICAL

anti-thymocyte globulin

fludarabine phosphate DRUG

fludarabine phosphate

Melphalan DRUG

melphalan

mycophenolate mofetil DRUG

mycophenolate mofetil

tacrolimus DRUG

tacrolimus

umbilical cord blood transplantation PROCEDURE

umbilical cord blood transplantation

Eligibility Criteria

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

DISEASE CHARACTERISTICS: * Diagnosis of hematologic malignancy for which a reduced-intensity allogeneic stem cell transplantation is deemed clinically appropriate, including any of the following: * Chronic myelogenous leukemia, meeting one of the following criteria: * In first chronic phase AND failed imatinib mesylate therapy, defined as failure to obtain a hematologic remission by 3 months or major cytogenetic response (Ph+ cells \< 35%) by 12 months, or demonstrated clonal evolution or disease progression while on therapy * In accelerated phase with \< 15% blasts * In blast crisis that has entered into a second chronic phase following induction chemotherapy * Acute myelogenous leukemia, meeting one of the following criteria: * In second or subsequent completion remission\* * Failed primary induction chemotherapy, but subsequently entered into a complete remission\* with ≤ 2 subsequent re-induction chemotherapy treatment(s) * In first complete remission\* with poor-risk cytogenetics NOTE: \*Complete remission is defined as \< 5% blasts in bone marrow, no definitive evidence of disease by morphology, flow cytometry, or genetic studies, and no circulating blasts. Neutrophil and platelet count recovery will not be required. * Acute lymphoblastic leukemia, meeting one of the following criteria: * In second or subsequent complete remission * In first complete remission AND t(9;22) * Myelodysplastic syndromes, meeting the following criteria: * High-risk disease, defined as International Prognostic Scoring System score of ≥ 1.5 * Less than 10% blasts at the time of study enrollment * Chronic myelomonocytic leukemia * Less than 10% blasts at the time of study enrollment * Myeloid metaplasia with myelofibrosis with poor-risk features, meeting one of the following criteria: * Age \< 55 years AND a Lille score of 1 * Lille score of 2 * Hemoglobin \< 10 g/dL AND abnormal karyotype * Chronic lymphocytic leukemia/prolymphocytic leukemia, meeting all of the following criteria: * Rai stage I-IV disease * Failed ≥ 1 prior chemotherapy regimen, including fludarabine, or autologous stem cell transplantation * Chemosensitive or stable, non-bulky disease prior to transplant * Received ≤ 3 prior chemotherapy regimens (monoclonal antibody therapy and involved-field radiotherapy are not considered prior regimens) * Low-grade B-cell non-Hodgkin lymphoma (NHL) (small lymphocytic lymphoma, follicular center \[grade 1 or 2\] lymphoma, or marginal zone lymphoma), meeting all of the following criteria: * Failed ≥ 1 prior chemotherapy regimen or autologous stem cell transplantation * Chemosensitive or stable, non-bulky disease prior to transplant * Received ≤ 3 prior chemotherapy regimens (monoclonal antibody therapy and involved-field radiotherapy are not considered prior regimens) * Intermediate-grade B-cell or T-cell NHL or mantle cell NHL, meeting all of the following criteria: * Failed to achieve remission or recurred after either conventional chemotherapy or autologous stem cell transplantation * Chemosensitive, non-bulky disease prior to transplant * Hodgkin lymphoma, meeting all of the following criteria: * Relapsed after prior autologous stem cell transplantation or after ≥ 2 combination chemotherapy regimens AND ineligible for autologous peripheral blood stem cell transplantation * Chemosensitive, non-bulky disease prior to transplant * Multiple myeloma, meeting one of the following criteria: * Relapsed after autologous stem cell transplantation * Relapsed after conventional therapies AND not a candidate for autologous stem cell transplantation * No HLA-matched related or unrelated donor available * Has two umbilical cord blood units available that are matched at ≥ 4/6 HLA A, B, and DRB1 with the patient and with each other (HLA C and DQ will not be used in the match strategy) * Total combined nucleated cell dose from the 2 umbilical cord blood units must be \> 3.7 x 10\^7 nucleated cells/kg (pre-freeze dose) NOTE: A new classification scheme for adult non-Hodgkin's lymphoma has been adopted by PDQ. The terminology of "indolent" or "aggressive" lymphoma will replace the former terminology of "low", "intermediate", or "high" grade lymphoma. However, this protocol uses the former terminology. PATIENT CHARACTERISTICS: * Karnofsky performance status 80-100% * Adapted, weighted Charlson Comorbidity Index \< 3 * Serum creatinine ≤ 2.0 mg/dL * AST or ALT \< 3 times upper limit of normal (ULN) * Bilirubin \< 1.5 times ULN * Not pregnant or nursing * LVEF ≥ 40% * DLCO \> 50% * No hypoxia at rest with oxygen saturation \< 92% on room air (corrected with bronchodilator therapy) * No active opportunistic infection (e.g., fungal pneumonia, tuberculosis, or viral infection) * No active hepatitis B or C infection that, in the opinion of a gastroenterologist or the transplant committee, places the patient at moderate- to high-risk for developing severe hepatic disease * No HIV infection PRIOR CONCURRENT THERAPY: * See Disease Characteristics

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

Sponsors & Collaborators

• Northside Hospital, Inc.: lead

Study Sites (1)

Blood and Marrow Transplant Group of Georgia

Atlanta, Georgia, 30342, United States

Location

MeSH Terms

Conditions

Myeloproliferative Disorders; Leukemia; Lymphoma; Multiple Myeloma; Neoplasms, Plasma Cell; Myelodysplastic Syndromes; Leukemia, Myeloid, Accelerated Phase; Congenital Abnormalities; Blast Crisis; Leukemia, Myelomonocytic, Chronic; Leukemia, Myeloid, Chronic-Phase; Leukemia, Prolymphocytic; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphocytic, Chronic, B-Cell; Hodgkin Disease; Lymphoma, Large-Cell, Anaplastic; Immunoblastic Lymphadenopathy; Lymphoma, T-Cell, Cutaneous; Mycosis Fungoides; Sezary Syndrome; Lymphoma, Extranodal NK-T-Cell; Waldenstrom Macroglobulinemia; Lymphoma, B-Cell, Marginal Zone; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Lymphoma, Follicular; Lymphoma, Mantle-Cell; Primary Myelofibrosis

Interventions

Antilymphocyte Serum; fludarabine phosphate; Melphalan; Mycophenolic Acid; Tacrolimus; Cord Blood Stem Cell Transplantation

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Cell Transformation, Neoplastic; Carcinogenesis; Neoplastic Processes; Myelodysplastic-Myeloproliferative Diseases; Leukemia, Lymphoid; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, B-Cell; Lymphoma, T-Cell; Lymphadenopathy; Lymphoma, B-Cell

Intervention Hierarchy (Ancestors)

Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids; Macrolides; Lactones; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative

Limitations and Caveats

This study was terminated early, therefore no additional data measures or outcomes are available.

Results Point of Contact

• Title: Scott R. Solomon, MD
• Organization: Blood and Marrow Transplant Group of Georgia

ssolomon@bmtga.com

404-255-1930

Study Officials

• Scott R. Solomon, MD

  Blood and Marrow Transplant Group of Georgia

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

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: January 21, 2009
• First Posted: January 22, 2009
• Study Start: June 1, 2006
• Primary Completion: November 1, 2009
• Study Completion: November 1, 2009
• Last Updated: March 23, 2012
• Results First Posted: August 3, 2011

Record last verified: 2012-03

Locations

US (1)