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Graft Versus Host DiseasePhase 1NCT00005988

Bone Marrow Transplantation With Specially Treated Bone Marrow in Treating Patients With Hematologic Cancer That Have Not Responded to Previous Therapy

A Phase 1 study testing cyclophosphamide, cyclosporine and leucovorin calcium in people with Graft Versus Host Disease and Leukemia, run by Dana-Farber Cancer Institute at 2 sites in United States.

Completed

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

Official record
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Trial summary

RATIONALE: Bone marrow transplantation may be able to replace immune cells that were destroyed by chemotherapy or radiation therapy used to kill tumor cells. Sometimes the transplanted cells can make an immune response against the body's normal tissues. Read more about this study

Who is it for?
Ages Up to 40 years
Conditions the study is for
Graft Versus Host Disease, Leukemia, Lymphoma
What is being tested?
cyclophosphamide, cyclosporine and leucovorin calcium
Could I receive a placebo?
No, everyone receives an active treatment
How many people
5 participants
Where
2 sitesUnited States
Study dates
Feb 2000to 8 Mar 2002
Phase
Phase 1
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 40 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • Age ≤40 years.
  • Diagnoses-patients with the following hematologic malignancies and bone marrow failure syndromes:
  • Acute myelogenous leukemia-induction failure, relapse, second or greater complete remission (CR)
  • Acute lymphocytic leukemia-induction failure, relapse, second or greater CR, first CR with t(9;22), t(8;14), or t(4;11)
  • Non-Hodgkin's lymphoma (intermediate or high grade) which has failed to achieve CR with at least two induction regimens, relapse, second or greater CR
  • Multiple myeloma with poor prognostic features (elevated 0-2 microglobulin or high labeling index)
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  • Hodgkin's disease in relapse or which fails to achieve CR after two chemotherapy regimens
  • Congenital or acquired bone marrow failure - poorly responsive to or intolerant of current therapy
  • Myelodysplastic syndrome of all subtypes except refractory anemia (RA)
  • Patient has a haploidentical family member that meets medical criteria for donation.
  • Eligibility for other transplant types:
  • Patient considered likely to have clinical deterioration and rapid disease progression during an unrelated donor search, or
  • Patient who has already had an unproductive donor search or
  • Patient ineligible for or has refused autologous transplant
  • Adequate renal and hepatic function for age:
  • Serum creatinine <2 x ULN
  • Alanine aminotransferase (ALT, SGPT) x ULN
  • Aspartate aminotransferase (AST, SGOT) x ULN
  • Total bilirubin 5_2 x ULN except if bilirubin is elevated due to Gilbert's syndrome or hemolytic anemia
  • Adequate cardiac and pulmonary function for age.
  • ECOG Performance Status 0, 1, or 2 or Lansky performance scale >50% for patients <16 years of age.
  • Voluntary witnessed written informed consent. Children will be asked for assent where appropriate.
  • The patient, if female, must be post-menopausal, premenarcheal, or sterile, or if the patient is of childbearing potential, she must be practicing a method of birth control considered effective and medically acceptable by the investigator for a minimum of 1 month prior to study entry and at least 2 months after the study end.
  • Patient must have undergone successful leukapheresis to obtain adequate antigen presenting cells.
  • Any patient who enters the study in a relapse state, with evidence of end organ (pulmonary, renal, or hepatic) toxicity, or with recent recovery from infection, who may potentially have little benefit from this protocol, must have his/her eligibility status discussed with the Principal Investigator.
  • Patient must have life expectancy of at least 12 weeks.

Who cannot join

  • Eligibility for other transplant types:
  • Patient has family donor who is matched or single antigen mismatched at HLA-A, HLA-B, HLA-DR, and HLA-DQ. Donorrecipient matching must be evaluated via both phenotype and genotype.
  • Patient has available unrelated donor who is matched at HLA-A, HLA-B, and HLA-DR. Donor-recipient matching must be evaluated via both phenotype and genotype.
  • Active uncontrolled infection (continued positive blood or soft tissue cultures despite appropriate antibiotic treatment)
  • Positive 13-HCG in a female of childbearing potential
  • Evidence of HIV infection or known HIV positive serology
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  • Any prior bone marrow transplant
  • A peripheral blood differential count at the time of leukapheresis with greater than 25% blasts. This exclusion criterion is valid only for the first four patients enrolled.
  • Patients with Fanconi's anemia

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02115

  • University of Minnesota Cancer Center

    Minneapolis, Minnesota, 55455

Other trials in United States

About this study

Official title: A Phase I Open-Label, Safety Study of Haploidentical Bone Marrow Transplantation (BMT) After Ex Vivo Treatment of Bone Marrow With Anti-B7.1 and Anti-B7.2 Antibodies

RATIONALE: Bone marrow transplantation may be able to replace immune cells that were destroyed by chemotherapy or radiation therapy used to kill tumor cells. Sometimes the transplanted cells can make an immune response against the body's normal tissues. Treatment of the donor bone marrow with the patient's white blood cells and a monoclonal antibody may prevent this from happening.

PURPOSE: Phase I trial to study the effectiveness of bone marrow transplantation with specially treated bone marrow in treating patients who have hematologic cancer that has not responded to previous therapy.

Read the detailed description

OBJECTIVES: I. Determine if patients with refractory, high risk hematologic malignancies or bone marrow failure who receive HLA haploidentical bone marrow treated with anti-B7 antibody have normal engraftment. II. Determine if these patients are free of hyperacute graft versus host disease (GVHD), defined as grade D GVHD in the first 10 posttransplant days, when treated with this regimen. III. Determine if these patients have an acceptable incidence of life threatening grade D GHVD in the first 50 posttransplant days following this treatment regimen. IV. Determine the safety and tolerability of this treatment regimen in this patient population.

OUTLINE: This is a multicenter study. Patients undergo leukapheresis to collect white blood cells which are incubated with donor bone marrow cells in the presence of anti-B7.1 and anti-B7.2 antibodies for 36 hours. Patients receive total body irradiation twice daily on days -6 to -3, cyclophosphamide IV daily on days -2 and -1, and methylprednisolone IV every 12 hours for a total of 4 doses on days -2 to 0. Patients are infused with the treated donor bone marrow on day 0. Patients then receive methotrexate IV on days 1, 3, 6, and 11 and leucovorin calcium IV 24 hours after each dose of methotrexate every 6 hours for 3-8 doses each time. Patients also receive cyclosporine IV or orally twice daily on days -2 to 100. Patients are followed every 2 months for 1 year.

PROJECTED ACCRUAL: A total of 20 patients will be accrued for this study.

Keywords
recurrent childhood acute lymphoblastic leukemia, recurrent adult Hodgkin lymphoma, refractory multiple myeloma, stage I multiple myeloma, stage II multiple myeloma, stage III multiple myeloma, stage I childhood lymphoblastic lymphoma, stage II childhood lymphoblastic lymphoma, stage III childhood lymphoblastic lymphoma, stage IV childhood lymphoblastic lymphoma, recurrent childhood lymphoblastic lymphoma, recurrent childhood acute myeloid leukemia, recurrent adult acute myeloid leukemia, recurrent adult acute lymphoblastic leukemia, childhood diffuse large cell lymphoma, childhood immunoblastic large cell lymphoma, adult acute myeloid leukemia in remission, adult acute lymphoblastic leukemia in remission, childhood acute myeloid leukemia in remission, childhood acute lymphoblastic leukemia in remission
Medical subject headings
Graft vs Host Disease, Leukemia, Lymphoma, Myelodysplastic Syndromes, Neoplasms, Plasma Cell, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Hodgkin Disease, Multiple Myeloma

What participants receive

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

Study groups in NCT00005988
Study groupRoleWhat they receive
in vitro-treated bone marrow transplantationExperimental* Donor bone marrow will be harvested on Day -2 * Bone Marrow incubated with irradiated recipient cells and anti-B7.1 and anti-B7.2 for 36 hours. * Bone marrow will be infused intravenously * Cyclophosphamide will be administered IV once daily * Total Body Irradiation (TBI) will be delivered per institutional practice * Methylprednisolone will be administered IV as 4 doses separated by 12 hours,
Receives: Drug: cyclophosphamide; Drug: cyclosporine; Drug: leucovorin calcium; Drug: methotrexate; Drug: methylprednisolone; Procedure: in vitro-treated bone marrow transplantation; Radiation: radiation therapy

What is being measured

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

  1. Incidence of primary graft failure

    Measured: up to 30 days post-transplant

Secondary outcomes (3)

  1. Incidence of hyperacute GVHD

    Measured: up to 100 days post-transplant

  2. Incidence of Grade D acute GVHD

    Measured: up to 50 days post-transplant

  3. Incidence of adverse events

    Measured: up to 100 days 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 posted3 May 2004 (estimated)
  2. Study startFeb 2000
  3. Primary completion16 Jun 2001
  4. Study completion8 Mar 2002

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 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
5 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00005988
Sponsor's protocol ID
99-205
Other IDs
P30CA006516, GENE-C9909-38, NCI-G00-1801, CDR0000067977
Status last verified
Mar 2017
First submitted
5 Jul 2000
Last updated
4 Apr 2017
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Davies JK, Gribben JG, Brennan LL, Yuk D, Nadler LM, Guinan EC. Outcome of alloanergized haploidentical bone marrow transplantation after ex vivo costimulatory blockade: results of 2 phase 1 studies. Blood. 2008 Sep 15;112(6):2232-41. doi: 10.1182/blood-2008-03-143636. Epub 2008 Jul 10.

    PubMed 18617635

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing cyclophosphamide, cyclosporine and leucovorin calcium in people with Graft Versus Host Disease and Leukemia, run by Dana-Farber Cancer Institute at 2 sites 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?

The sponsor lists 26 inclusion and 9 exclusion criteria. 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 4 Apr 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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?

Incidence of primary graft failure (time frame: up to 30 days post-transplant). 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 NCT00005988, which also lists 1 linked publication.

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 4 Apr 2017.

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Clinical Trial NCT00005988 | AzTrials