Pilot Trial of Targeted Immune-Depleting Chemotherapy and Reduced-Intensity Matched Unrelated Double Cord Blood Transplant for the Treatment of Leukemias, Lymphomas, and Pre-Malignant Blood Disorders

NCT00973804 | Terminated Phase 1

• 2 other identifiers: 09021009-C-0210
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

Background:

• Allogeneic stem cell transplantation (SCT) has been used to treat many kinds of cancer or pre-cancerous conditions that develop in blood or immune system cells. Umbilical cord blood transplantation (UCBT) is a type of allogeneic transplant that is used when none of a patient s siblings are a match and an acceptable match cannot be identified from one of the bone marrow registries. Prior to receiving the cord blood stem cells, large doses of chemotherapy drugs and/or radiation have been traditionally used to eliminate most of the cancerous or abnormal cells from the recipient s system, along with most of his or her own stem cells and immune cells. Donor stem cells then replace the recipient s stem cells in the bone marrow, restoring normal blood production and immunity. In this way, an allogeneic SCT provides not only new blood cells but an entire new immune system.
• In the past, allogeneic SCT was performed with very high doses of chemotherapy and/or radiation to get rid of as much of the recipient s cancer as possible and prevent rejection of the treatment. However, intensive chemotherapy or radiation can cause serious side effects, including death. A newer method uses smaller, less toxic doses of chemotherapy and/or radiation before allogeneic SCT. In these reduced-intensity stem cell transplants, the recipient s stem cells and immunity are not completely eliminated, but they are weakened enough to help prevent the donor s cells from being rejected. Objectives: \- To study the safety and effectiveness of reduced-intensity stem cell transplants given with immune-depleting chemotherapy and umbilical cord blood provided by an unrelated donor. Eligibility:
• Individuals between 18 and 69 years of age who have been diagnosed with any of a number of cancerous and pre-cancerous blood conditions, including lymphoma and leukemia.
• Participants must not have a potential donor sibling or a readily available unrelated donor identified through one of the bone marrow donor registries. Design:
• Patients will be matched with at least two umbilical cords with an acceptable cell dose. The two frozen umbilical cord blood units will be sent to the NIH prior to the date of transplant.
• Patients will receive one, two, or three cycles of chemotherapy (based on the type of disease) to treat the disease and to weaken the immune system. Patients who already have a weakened immune system from other treatments will not receive this round of chemotherapy.
• Patients will then receive 4 days of reduced-intensity transplant chemotherapy (also called the conditioning regimen ) to prepare for the transplant.
• Two days after transplant chemotherapy, patients will receive the transplant, with the two umbilical cords infused one after the other on the same day. Patients will receive additional treatment to prevent complications.
• Patients will remain in the hospital for 4 to 6 weeks after the transplant, and will be discharged for outpatient treatment when the study doctors deem it appropriate.
• Patients will continue on medications at home to lower the risk of complications and infections, and will visit the NIH clinic regularly for the first 6 months after the transplant, and then less often for at least 5 years afterward.

Conditions

Leukemia; Non-Hodgkins Lymphoma; Hodgkins Lymphoma; MDS; Multiple Myeloma

Keywords

Reduced Intensity Conditioning; Umbilical Cord Blood Transplant; Targeted Immune Depletion; Leukemia; Lymphoma; Multiple Myeloma; Non-Hodgkins Lymphoma; Hodgkins Lymphoma

Outcome Measures

Primary Outcomes (1)

• The primary objective of this study is to see whether targeted immune depletion can shorten the time to hematopoietic recovery and improve cord blood engraftment rate as measured by ANC greater than 500 X 3 and at least partial donor chimerism (...

Secondary Outcomes (1)

• Secondary objectives include further assessment of immune reconstitution, study of engraftment kinetics in relation to cell dose and HLA-match, and comprehensive assessment of acute and chronic GVHD.

Interventions

EPOCH-F/R DRUG

FLAG DRUG

Transplant Preparative Regimen (Flu/Cy/Mes) DRUG

GVHD Prophylaxis (tacrolimus and sirolimus) DRUG

Double Cord Blood Transplantation PROCEDURE

Eligibility Criteria

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

* ELIGIBILITY CRITERIA: * Adults (18-69 years) with advanced or high-risk hematologic malignancies including AML, ALL, MDS, CLL, NHL, HL, CML, multiple myeloma, and MPD who lack a readily available HLA-matched sibling or greater than or equal to 7/8 HLA-matched unrelated donor. Patients must have life expectancy of at least 3 months, ECOG less than or equal to 2, and relatively normal major organ functions. * Patients must have two partially HLA-matched UCB units. Units must be HLA-matched at HLA-A and B (intermediate resolution molecular typing) and DRB1 (high resolution molecular typing) 4-6/6 with the recipient and 4-6/6 with each other. Each unit must contain a minimum precryopreserved, nucleated cell dose of 1.5 x 10(7) per kilogram.

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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Laughlin MJ, Eapen M, Rubinstein P, Wagner JE, Zhang MJ, Champlin RE, Stevens C, Barker JN, Gale RP, Lazarus HM, Marks DI, van Rood JJ, Scaradavou A, Horowitz MM. Outcomes after transplantation of cord blood or bone marrow from unrelated donors in adults with leukemia. N Engl J Med. 2004 Nov 25;351(22):2265-75. doi: 10.1056/NEJMoa041276.

  PMID: 15564543 BACKGROUND

• Rocha V, Labopin M, Sanz G, Arcese W, Schwerdtfeger R, Bosi A, Jacobsen N, Ruutu T, de Lima M, Finke J, Frassoni F, Gluckman E; Acute Leukemia Working Party of European Blood and Marrow Transplant Group; Eurocord-Netcord Registry. Transplants of umbilical-cord blood or bone marrow from unrelated donors in adults with acute leukemia. N Engl J Med. 2004 Nov 25;351(22):2276-85. doi: 10.1056/NEJMoa041469.

  PMID: 15564544 BACKGROUND

• Bishop MR, Steinberg SM, Gress RE, Hardy NM, Marchigiani D, Kasten-Sportes C, Dean R, Pavletic SZ, Gea-Banacloche J, Castro K, Hakim F, Krumlauf M, Read EJ, Carter C, Leitman SF, Fowler DH. Targeted pretransplant host lymphocyte depletion prior to T-cell depleted reduced-intensity allogeneic stem cell transplantation. Br J Haematol. 2004 Sep;126(6):837-43. doi: 10.1111/j.1365-2141.2004.05133.x.

  PMID: 15352988 BACKGROUND

MeSH Terms

Conditions

Leukemia; Lymphoma, Non-Hodgkin; Hodgkin Disease; Multiple Myeloma; Lymphoma

Interventions

Tacrolimus; Sirolimus

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Study Officials

• Steven Z Pavletic, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH

Study Record Dates

• First Submitted: September 5, 2009
• First Posted: September 9, 2009
• Study Start: August 25, 2009
• Primary Completion: May 20, 2013
• Study Completion: May 20, 2013
• Last Updated: December 17, 2019

Record last verified: 2013-05-20

Locations

US (1)