AzTrials
AzTrials

Graft Versus Host DiseasePhase 2NCT00003335

Umbilical Cord Blood Transplantation in Treating Patients With High-Risk Hematologic Cancer

A Phase 2 study testing anti-thymocyte globulin, busulfan and cyclosporine in people with Graft Versus Host Disease and Leukemia, run by Case Comprehensive Cancer Center at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

RATIONALE: Umbilical cord blood transplantation may allow doctors to give higher doses of chemotherapy or radiation therapy and kill more cancer cells. PURPOSE: This phase II trial is studying allogeneic umbilical cord blood transplantation to see how well it works when given with chemotherapy or radiation therapy in… Read more about this study

Who is it for?
Ages Up to 54 years
Conditions the study is for
Graft Versus Host Disease, Leukemia, Lymphoma
What is being tested?
anti-thymocyte globulin, busulfan and cyclosporine
How many people
44 participants
Where
1 siteUnited States
Study dates
Jan 1998to Jan 2012
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Up to 54 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

DISEASE CHARACTERISTICS:

  • Histologically confirmed high risk malignancy including:
  • Acute nonlymphocytic leukemia (ANLL) after induction failure, or in first complete remission with high risk features including stem cell or biphenotypic classification (acute myeloid leukemia (AML) M0), erythroleukemia (AML M6), acute megakaryocytic leukemia (AML M7), cytogenic markers indicative of poor prognosis, or failure to achieve complete remission after standard induction therapy
  • Acute lymphocytic leukemia (ALL) or ANLL in second or subsequent remission
  • Chronic myeloid leukemia (CML) in chronic phase
  • CML with accelerated phase or blast crisis are eligible after reinduction chemotherapy converts disease to chronic phase
  • High risk ALL in first complete remission
  • Myelodysplastic syndrome with evidence of evolution to acute myeloid leukemia
  • Refractory anemia with excess blasts
  • Refractory anemia with excess blasts in transformation
  • Non-Hodgkin's lymphoma (NHL), ANLL, or ALL with recurrent disease after autologous stem cell transplantation
  • Must also meet all the following conditions:
  • No HLA-ABC/DR identical related bone marrow or UCB donor
  • No 5/6 antigen matched related bone marrow or UCB donor
  • Condition precludes waiting to search and find a donor in the National Marrow Donor Registry
  • Must have an available serologic matched umbilical cord blood unit in the New York Blood Center's Placental Blood Project
  • No active CNS disease

PATIENT CHARACTERISTICS:

Age:

  • Under 55 at time of umbilical cord blood transplantation

Performance status:

  • Zubrod 0-1
  • Karnofsky 80-100%

Life expectancy:

  • At least 3 months

Hematopoietic:

  • For patients with ALL or ANLL in remission, CML in chronic phase, or NHL without marrow involvement who elect to undergo autologous peripheral blood stem cell collection and storage:
  • WBC at least 3,000/mm^3
  • Absolute neutrophil count at least 1,000/mm^3
  • Platelet count at least 100,000/mm^3

Hepatic:

  • Bilirubin no greater than 2.0 mg/dL
  • ALT/AST no greater than 4 times normal

Renal:

  • Creatinine no greater than 2.0 mg/dL
  • Creatinine clearance at least 50 mL/min

Cardiovascular:

  • Normal cardiac function by echocardiogram or radionuclide scan (shortening fraction or ejection fraction at least 80% of normal value for age)

Pulmonary:

  • FVC and FEV_1 at least 60% of predicted for age
  • For adults:
  • DLCO at least 60% of predicted

Other:

  • HIV negative
  • No active infections at time of autologous stem cell harvest or pretransplant cytoreduction
  • Not pregnant or nursing
  • Effective contraception required of all fertile patients

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • Prior autologous stem cell transplantation allowed

Chemotherapy:

  • See Disease Characteristics

Endocrine therapy:

  • Not specified

Radiotherapy:

  • Not specified

Surgery:

  • Not specified

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center

    Cleveland, Ohio, 44106-5065

Other trials in United States

About this study

Official title: A Pilot Study of Unrelated Umbilical Cord Blood Transplantation in Patients With High Risk Hematologic Malignancies

RATIONALE: Umbilical cord blood transplantation may allow doctors to give higher doses of chemotherapy or radiation therapy and kill more cancer cells.

PURPOSE: This phase II trial is studying allogeneic umbilical cord blood transplantation to see how well it works when given with chemotherapy or radiation therapy in treating patients with high-risk hematologic cancer.

Read the detailed description

OBJECTIVES:

  • Determine the rates of hematologic and immune reconstitution in patients with high risk hematologic malignancies who are undergoing high dose chemoradiotherapy followed by unrelated umbilical cord blood (UCB) transplantation.
  • Determine the incidence of graft-versus-host-disease in this setting.
  • Describe the incidence of recurrent disease in these patients post UCB transplant.
  • Describe the incidence of serious infections and secondary lymphoproliferative diseases following transplantation with UCB in these patients.
  • Determine specifically whether larger recipients can be durably engrafted with unrelated UCB, and determine whether nucleated cell or progenitor cell content of the graft is predictive of hematological engraftment.

OUTLINE: Patients may undergo a back-up peripheral blood stem cell collection prior to treatment.

Patients receive 9 fractions of total body irradiation (TBI) on days -9 to -5 followed by melphalan IV for three days on days -4 to -2 and antithymocyte globulin IV or methylprednisolone IV for three days on days -3 to -1. On day 0, patients receive umbilical cord blood infusion. If TBI is not tolerated, busulfan is substituted and administered orally every 6 hours for 4 days on days -8 to -5. Cyclosporine and methylprednisolone begin on day -2 and continue for 6 months.

Patients are followed at least monthly for 1 year, then every 6 months for the second year, and then annually thereafter.

PROJECTED ACCRUAL: There will be a maximum of 48 patients accrued into this study over 4 years.

Being tested
anti-thymocyte globulin, busulfan, cyclosporine, melphalan, methylprednisolone
Keywords
recurrent childhood acute lymphoblastic leukemia, recurrent childhood lymphoblastic lymphoma, recurrent adult acute lymphoblastic leukemia, chronic phase chronic myelogenous leukemia, accelerated phase chronic myelogenous leukemia, blastic phase chronic myelogenous leukemia, untreated childhood acute lymphoblastic leukemia, adult acute myeloid leukemia in remission, adult acute lymphoblastic leukemia in remission, childhood acute myeloid leukemia in remission, childhood acute lymphoblastic leukemia in remission, adult acute erythroid leukemia (M6), adult acute megakaryoblastic leukemia (M7), childhood acute erythroleukemia (M6), childhood acute megakaryocytic leukemia (M7), refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, recurrent grade 3 follicular lymphoma
Medical subject headings
Graft vs Host Disease, Leukemia, Lymphoma, Myelodysplastic Syndromes, Myelodysplastic-Myeloproliferative Diseases, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Myeloid, Chronic-Phase, Leukemia, Myeloid, Accelerated Phase

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • anti-thymocyte globulinBiological

    antithymocyte globulin IV for three days on days -3 to -1

  • busulfanDrug

    If TBI is not tolerated, busulfan is substituted and administered orally every 6 hours for 4 days on days -8 to -5.

  • cyclosporineDrug

    Cyclosporine begin on day -2 and continue for 6 months.

  • melphalanDrug

    melphalan IV for three days on days -4 to -2

  • methylprednisoloneDrug

    Methylprednisolone IV for three days on days -3 to -1. Methylprednisolone begin on day -2 and continue for 6 months.

  • umbilical cord blood transplantationProcedure or surgery

    On day 0, patients receive umbilical cord blood infusion.

  • radiation therapyRadiation

    9 fractions of total body irradiation (TBI) on days -9 to -5

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. rates of durable engraftment in patients

    The primary study end point will be hematologic engraftment. Engraftment is defined as achieving ANC larger than or equal to 500 ul/mm3 of donor origin for three consecutive measurements on different days by day +42.

    Measured: day 42

Secondary outcomes (2)

  1. Event-free survival by clinical and pathological disease assessment

    Measured: at disease progression or death

  2. incidence of recurrent disease in patients post UCB transplant

    Measured: post transplant

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Jan 2003 (estimated)
  2. Study startJan 1998
  3. Primary completionNov 2007
  4. Study completionJan 2012

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
44 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00003335
Sponsor's protocol ID
CWRU4Y97
Other IDs
P30CA043703, NCI-G98-1429, CWRU4Y97
Status last verified
Mar 2012
First submitted
1 Nov 1999
Last updated
15 Mar 2012
Results posted
No
Data monitoring committee
Yes

Publications

  • Lesniewski ML, Haviernik P, Weitzel RP, Kadereit S, Kozik MM, Fanning LR, Yang YC, Hegerfeldt Y, Finney MR, Ratajczak MZ, Greco N, Paul P, Maciejewski J, Laughlin MJ. Regulation of IL-2 expression by transcription factor BACH2 in umbilical cord blood CD4+ T cells. Leukemia. 2008 Dec;22(12):2201-7. doi: 10.1038/leu.2008.234. Epub 2008 Sep 4.

    PubMed 18769450

  • van Heeckeren WJ, Fanning LR, Meyerson HJ, Fu P, Lazarus HM, Cooper BW, Tse WW, Kindwall-Keller TL, Jaroscak J, Finney MR, Fox RM, Solchaga L, Forster M, Creger RJ, Laughlin MJ. Influence of human leucocyte antigen disparity and graft lymphocytes on allogeneic engraftment and survival after umbilical cord blood transplant in adults. Br J Haematol. 2007 Nov;139(3):464-74. doi: 10.1111/j.1365-2141.2007.06824.x.

    PubMed 17910637

  • Kindwall-Keller TL, Hegerfeldt Y, Meyerson HJ, Margevicius S, Fu P, van Heeckeren W, Lazarus HM, Cooper BW, Gerson SL, Barr P, Tse WW, Curtis C, Fanning LR, Creger RJ, Carlson-Barko JM, Laughlin MJ. Prospective study of one- vs two-unit umbilical cord blood transplantation following reduced intensity conditioning in adults with hematological malignancies. Bone Marrow Transplant. 2012 Jul;47(7):924-33. doi: 10.1038/bmt.2011.195. Epub 2011 Oct 17.

    PubMed 22002488

  • Weitzel RP, Lesniewski ML, Haviernik P, Kadereit S, Leahy P, Greco NJ, Laughlin MJ. microRNA 184 regulates expression of NFAT1 in umbilical cord blood CD4+ T cells. Blood. 2009 Jun 25;113(26):6648-57. doi: 10.1182/blood-2008-09-181156. Epub 2009 Mar 13.

    PubMed 19286996

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing anti-thymocyte globulin, busulfan and cyclosporine in people with Graft Versus Host Disease and Leukemia, run by Case Comprehensive Cancer Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 15 Mar 2012. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

rates of durable engraftment in patients (time frame: day 42). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00003335, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Mar 2012.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Keep searching with a free account

You’ve used your 3 free searches for this session. Log in or create a free AzTrials account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in
Clinical Trial NCT00003335 | AzTrials