Pooled Unrelated Donor Umbilical Cord Blood Transplant For Hematologic Malignancy Needing Allogeneic Stem Cell Transplant Without Related HLA-Match

NCT01500161 | Terminated Phase 2 DMC

• 1 other identifier: 1127920
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the multi-lineage hematopoietic chimerism for unrelated umbilical cord blood (UCB) grafts pooled from two to three cord blood units. Also to evaluate the toxicity, and antitumor responses of pooled unrelated UCB transplants.

Conditions

Acute Myelogenous Leukemia; Acute Lymphocytic Leukemia; Chronic Lymphocytic Leukemia; Chronic Myelogenous Leukemia; Hodgkins Disease; Non-Hodgkins Lymphoma; Aplastic Anemia; Multiple Myeloma; Myelodysplastic Syndrome

Keywords

Leukemia; Lymphoma; Myeloma; Aplastic Anemia; Myelodysplasia; AML; ALL; CLL; CML

Outcome Measures

Primary Outcomes (1)

• evaluate the multi-lineage hematopoietic chimerism for unrelated UCB grafts pooled from two to three cord blood units

  Blood will be obtained for DNA preparation for VNTR chimerism study post transplant after time of engraftment, which will happen at an average of 28 days post-trasplant.

  Will be tested after granulocyte engraftment - which will happen at an average of 28 days post-transpant

Secondary Outcomes (3)

• evaluate the antitumor responses of pooled UCB transplant

  Disease staged at baseline, then disease status re-assessed at 6 weeks, 3 months, 6 months, 9 months, 12 months and after that every 6 months post-transplant

• Number of participants that develop Graft Versus Host Disease after pooled UCB transplant

  Patients will be assessed weekly during first 28 days then re-assessed at 6 weeks, 3 months, 6 months, 9 months, 12 months and after that every 6 months post-transplant.

• The Infection rate seen in the participants who received a pooled UCB transplant

  Patients will be assessed weekly during first 28 days then re-assessed at 6 weeks, 3 months, 6 months, 9 months, 12 months and after that every 6 months post-transplant.

Study Arms (1)

Single Arm

EXPERIMENTAL

The following conditioning regimens will be used, depending on the underlying hematologic malignancies. Conditioning regimens with Busulfan/clofarabine and with fludarabine/melphalan will be used for all patients except those with Non-Hodgkin's lymphoma when the conditioning regimen of BCNU, Etoposide, ARA-C and Melphalan will be used.

Drug: Busulfan; Drug: Clofarabine; Drug: Fludarabine; Drug: Melphalan; Drug: Carmustine; Drug: Etoposide; Drug: Cytarabine

Interventions

Busulfan DRUG

Busulfan 3.2 mg/kg/day intravenously on days -7, -6, -5 and -4(for non-NHL patients patients who get Clofarabine regimen)

Single Arm

Clofarabine DRUG

Clofarabine intravenously 40 mg/m2/day on days -7, -6, -5, -4 and -3(for non-NHL patients patients who get Busulfan regimen)

Single Arm

Fludarabine DRUG

Fludarabine 30 mg/kg/day intravenously on days -7, -6, -5, -4 and -3 (for non-NHL patients who receive Melphalan containing regimen)

Single Arm

Melphalan DRUG

Melphalan intravenously 140 mg/m2/day on day -3 (only for non-NHL patients who receive Fludarabine OR for all NHL regimens)

Single Arm

Carmustine DRUG

BCNU(Carmustine)300 mg/m2 intravenously on day -7 (for NHL patients only)

Single Arm

Etoposide DRUG

Etoposide 300 mg/m2/day intravenously on days -6, -5, -4 and -3 (for NHL patients only)

Single Arm

Cytarabine DRUG

ARA-C(Cytarabine) 100 mg/m2/day on days -6, -5, -4 and -3 (for NHL patients only)

Single Arm

Eligibility Criteria

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

You may qualify if:

• Patients \< 65 years with hematologic malignancies needing stem cell transplant but do not have HLA-matched sibling donor. Patients with the following diagnosis will be included:
• AML in first or subsequent complete or partial remissions
• ALL in first or subsequent complete or partial remissions
• CLL in second remission or more advanced disease
• CML who has failed tyrosine kinase inhibitors
• Hodgkin's disease who relapse after autologous transplant
• Non-Hodgkin's lymphoma who relapse after autologous transplant or NK-cell lymphoma in CR1
• Aplastic anemia patients
• Multiple myeloma in second remission or moer advanced disease, including those who have failed an autologous transplant
• Myelodysplastic syndrome in first or subsequent complete or partial remission
• Patients must have 6/6, 5/6 or 4/6 molecular matches from unrelated UCB donors. Matching will be done for A, B, and DR. Matching at DR will be confirmed by molecular typing.
• Patients must be documented to be HIV negative. Screening must have been performed within previous 6 months.
• Patients must be able to give written consent.

Sponsors & Collaborators

• Texas Oncology Cancer Center: lead

Study Sites (1)

Texas Oncology

Amarillo, Texas, 79106, United States

Location

Related Publications (8)

• Balduzzi A, Gooley T, Anasetti C, Sanders JE, Martin PJ, Petersdorf EW, Appelbaum FR, Buckner CD, Matthews D, Storb R, Sullivan KM, Hansen JA. Unrelated donor marrow transplantation in children. Blood. 1995 Oct 15;86(8):3247-56.

  PMID: 7579422 BACKGROUND

• Petersdorf EW, Longton GM, Anasetti C, Martin PJ, Mickelson EM, Smith AG, Hansen JA. The significance of HLA-DRB1 matching on clinical outcome after HLA-A, B, DR identical unrelated donor marrow transplantation. Blood. 1995 Aug 15;86(4):1606-13.

  PMID: 7632970 BACKGROUND

• Laughlin MJ, Barker J, Bambach B, Koc ON, Rizzieri DA, Wagner JE, Gerson SL, Lazarus HM, Cairo M, Stevens CE, Rubinstein P, Kurtzberg J. Hematopoietic engraftment and survival in adult recipients of umbilical-cord blood from unrelated donors. N Engl J Med. 2001 Jun 14;344(24):1815-22. doi: 10.1056/NEJM200106143442402.

  PMID: 11407342 BACKGROUND

• Wagner JE, Kernan NA, Steinbuch M, Broxmeyer HE, Gluckman E. Allogeneic sibling umbilical-cord-blood transplantation in children with malignant and non-malignant disease. Lancet. 1995 Jul 22;346(8969):214-9. doi: 10.1016/s0140-6736(95)91268-1.

  PMID: 7616801 BACKGROUND

• Wagner JE, Rosenthal J, Sweetman R, Shu XO, Davies SM, Ramsay NK, McGlave PB, Sender L, Cairo MS. Successful transplantation of HLA-matched and HLA-mismatched umbilical cord blood from unrelated donors: analysis of engraftment and acute graft-versus-host disease. Blood. 1996 Aug 1;88(3):795-802.

  PMID: 8704232 BACKGROUND

• Kurtzberg J, Laughlin M, Graham ML, Smith C, Olson JF, Halperin EC, Ciocci G, Carrier C, Stevens CE, Rubinstein P. Placental blood as a source of hematopoietic stem cells for transplantation into unrelated recipients. N Engl J Med. 1996 Jul 18;335(3):157-66. doi: 10.1056/NEJM199607183350303.

  PMID: 8657213 BACKGROUND

• Gluckman E, Rocha V, Boyer-Chammard A, Locatelli F, Arcese W, Pasquini R, Ortega J, Souillet G, Ferreira E, Laporte JP, Fernandez M, Chastang C. Outcome of cord-blood transplantation from related and unrelated donors. Eurocord Transplant Group and the European Blood and Marrow Transplantation Group. N Engl J Med. 1997 Aug 7;337(6):373-81. doi: 10.1056/NEJM199708073370602.

  PMID: 9241126 BACKGROUND

• Rubinstein P, Carrier C, Scaradavou A, Kurtzberg J, Adamson J, Migliaccio AR, Berkowitz RL, Cabbad M, Dobrila NL, Taylor PE, Rosenfield RE, Stevens CE. Outcomes among 562 recipients of placental-blood transplants from unrelated donors. N Engl J Med. 1998 Nov 26;339(22):1565-77. doi: 10.1056/NEJM199811263392201.

  PMID: 9828244 BACKGROUND

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Hodgkin Disease; Lymphoma, Non-Hodgkin; Anemia, Aplastic; Multiple Myeloma; Myelodysplastic Syndromes; Leukemia; Lymphoma; Neoplasms, Plasma Cell; Anemia, Refractory, with Excess of Blasts

Interventions

Busulfan; Clofarabine; fludarabine; Melphalan; Carmustine; Etoposide; Cytarabine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Adenine Nucleotides; Purine Nucleotides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Nucleotides; Ribonucleotides; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Nitrosourea Compounds; Urea; Amides; Nitroso Compounds; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Seah Lim, MD

  Texas Oncology - Amarillo,TX

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principle Investigator

Study Record Dates

• First Submitted: November 18, 2011
• First Posted: December 28, 2011
• Study Start: November 1, 2011
• Primary Completion: November 1, 2013
• Study Completion: November 1, 2013
• Last Updated: November 25, 2013

Record last verified: 2013-11

Locations

US (1)