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Hodgkin's DiseasePhase 2NCT00597714

Efficacy Study of T Cell Depleted Allogeneic Non-myeloablative Stem Cell Transplant

A Phase 2 study testing Non-myeloablative Stem Cell Transplantation in people with Hodgkin's Disease and Non Hodgkin's Lymphoma, run by David Rizzieri, MD 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
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Trial summary

The central hypothesis of this study is that use of a less toxic chemotherapy preparative regimen for allogeneic hematopoietic stem cell transplantation in combination with T cell depletion with alemtuzumab for patients with high risk hematologic malignancies will allow effective control of disease and improved… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Hodgkin's Disease, Non Hodgkin's Lymphoma, Myeloma
What is being tested?
Non-myeloablative Stem Cell Transplantation
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
264 participants
Where
1 siteUnited States
Study dates
Feb 2008to Nov 2013
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Recipient Inclusion Criteria:

  • Subjects must have their diagnosis confirmed at the transplant center.
  • Performance status must be Cancer and Leukemia Group B (CALGB) = 0, 1, or 2.
  • Subjects must have a 3-6/6 human leukocyte antigen (HLA)-matched related donor or 8/8 or better allele level match matched unrelated donor (MUD) (at A,B, C, DRB1, DQ).
  • HIV negative.
  • Women of child bearing potential must have a negative pregnancy test within 1 week of starting therapy.
  • Subjects > or equal to 18 years of age are eligible.
  • Subjects must have a Multi Gated Acquisition Scan (MUGA) and/or Echocardiography (ECHO) or cardiac magnetic resonance (MR) and or diffusing capacity testing of the lung for carbon monoxide (DLCO) performed before transplant.
  • Specific populations:
  • Group A) Subjects with a high chance of progressive lymphoid or myelomatous diseases.
  • Group B) Subjects with a high chance of progressive myeloid diseases, marrow failure syndromes or myeloproliferative disorders

Recipient Exclusion Criteria:

  • Pregnant or lactating women.
  • Subjects with other major medical or psychiatric illnesses which the treating physician feels could seriously compromise tolerance to this protocol.
  • Subjects with uncontrolled, progressive infections.
  • Subjects who are good candidates for long term disease control with standard chemotherapy or radiation or high dose therapy and autologous support.
  • Subjects with active central nervous system (CNS) disease.

Donor Inclusion Criteria:

  1. Donor must be capable of providing informed consent. If 14-17 years of age, a 'single patient exemption' from the local Institutional Review Board must be obtained.
  2. Donor must not have any medical condition which would make mobilization or apheresis more than a minimal risk, and should have the following:
  3. Adequate cardiac function by history and physical examination. Those with a history of cardiac failure or infarction should be evaluated by a cardiologist prior to donation
  4. Adequate hematopoietic function with hematocrit ≥ 30%, white blood cell count of 3000, and platelets 100,000.
  5. Females should not be pregnant or lactating and have a negative serum pregnancy test within 1 week of beginning mobilization if of child bearing potential.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Duke University Health System

    Durham, North Carolina, 27710

Other trials in United States

About this study

Official title: Efficacy Study of T Cell Depleted Allogeneic Non-myeloablative Stem Cell Transplantation

The central hypothesis of this study is that use of a less toxic chemotherapy preparative regimen for allogeneic hematopoietic stem cell transplantation in combination with T cell depletion with alemtuzumab for patients with high risk hematologic malignancies will allow effective control of disease and improved disease free and overall survival compared with historical expectations. Specifically, the objectives are to estimate toxicity, disease free, progression free, event free, and overall survival rates in patients treated with alemtuzumab T cell depleted, reduced intensity preparative regimen followed by allogeneic hematopoietic transplantation; evaluate immune recovery following this reduced intensity allogeneic immunotherapy; develop an in vitro assay to allow patient individualized targeted dosing.

Read the detailed description

The central hypothesis of this study is that use of a less toxic chemotherapy preparative regimen for allogeneic hematopoietic stem cell transplantation in combination with T cell depletion with alemtuzumab for patients with high risk hematologic malignancies will allow effective control of disease and improved disease free and overall survival compared with historical expectations. Specifically, the objectives are to estimate toxicity, disease free, progression free, event free and overall survival rates in patients treated with an alemtuzumab T cell depleted, reduced intensity preparative regimen followed by allogeneic hematopoietic transplantation; evaluate immune recovery following this reduced intensity allogeneic immunotherapy; develop an in vitro assay to allow patient individualized targeted dosing. The study population is HIV negative, adult patients who are not pregnant but have confirmed diagnosis of disease; must have Cancer and Leukemia Group B (CALGB) performance status (PS) 0, 1, or 2; must have a 3-6/6 human leukocyte antigen (HLA)-matched related donor or 8/8 (A, B, C, DRB1, DQ are the primary determinants) or better HLA-matched unrelated donor who is evaluated and deemed able to provide peripheral blood stem cells (PBPCs) and/or marrow by the transplant team. The target population of patients is those with a high chance of progressive lymphoid or myelomatous diseases, progressive myeloid diseases, marrow failure syndromes or myeloproliferative disorders.

Being tested
Non-myeloablative Stem Cell Transplantation
Keywords
Stem Cell Transplantation, Non-myeloablative
Medical subject headings
Hodgkin Disease, Lymphoma, Non-Hodgkin, Neoplasms, Plasma Cell, Leukemia, Anemia, Refractory, with Excess of Blasts

What participants receive

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

  • Non-myeloablative Stem Cell TransplantationDrug

    Also called Allogeneic Stem Cell Transplant

    The preparative regimen is 4 days of daily fludarabine at 40 mg/m2/d infused over 30 minutes; melphalan 140 mg/m2/d for 1 day administered over 15 minutes; 4 days of Alemtuzumab at 20 mg/d in 250 ml of normal saline infused over 3 hours. Group B's prep regimen will begin on day -5 or day -4 and busulfan 130mg/m2/d for 2 days over 3 hours. The peripheral blood stem cells (PBSCs) will be infused over 2-4 days. Patient evaluations will occur 2 times per week by physical exam for toxicity through day 45.

Study groups in NCT00597714
Study groupRoleWhat they receive
Cohort A - Lymphoid DiseaseExperimentalGroup A: Patients with a high chance of progressive lymphoid or myelomatous disease undergo Non-myeloablative Stem Cell Transplantation.
Receives: Drug: Non-myeloablative Stem Cell Transplantation
Cohort B - Myeloid DiseaseExperimentalGroup B: Patients with a high chance of progressive myeloid diseases, marrow failure syndromes or myeloproliferative disorders undergo Non-myeloablative Stem Cell Transplantation.
Receives: Drug: Non-myeloablative Stem Cell Transplantation
DonorNo interventionDonor priming and apheresis will include filgrastim 8 mcg/kg subcutaneously twice daily for 4 days prior to stem cell collection and continuing until pheresis is completed. Alternative mobilization strategies may be employed at the investigator's discretion.

What is being measured

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

  1. Disease Free Survival

    Estimate disease free survival rates in participants treated with an alemtuzumab T cell depleted, reduced intensity preparative regimen followed by allogeneic hematopoietic transplantation. Disease-free survival (DFS), progression-free survival (PFS), and overall survival (OS) rates after SCT were estimated using the Kaplan-Meier method. We performed univariate comparisons by using the log-rank test. DFS was defined as the period of time between the day of transplantation and either disease relapse or death due to the disease. The following variables were considered as confounders: recipient age, recipient sex, disease (myeloid or lymphoid), disease risk (standard or high), and donor type (MRD, MUD, or HAPLO donor). The percentage of participants who were disease free at 2 years is reported by donor type.

    Measured: 2 years

Secondary outcomes (4)

  1. Immune Recovery

    Evaluate immune recovery following this reduced intensity allogeneic immunotherapy. Quantification of CD3+, CD4+, and CD8+ T cells was performed by flow cytometry on fresh peripheral blood at approximately 1 month before transplantation and then 1.5, 3, 6, and 12 months after transplantation. The immune recovery rates of the CD3+, CD4+, and CD8+ T cells in the MRD, MUD, and HAPLO groups were compared by performing an analysis of variance at each time point after transplantation. The median T cell counts at 12 months for each type of cell are reported by donor type.

    Measured: 1 year

  2. Progression Free Survival

    Progression-free survival (PFS) rates after stem cell transplant were estimated using the Kaplan-Meier method. We performed univariate comparisons by using the log-rank test. PFS was defined as the period of time between the day of transplantation and either the day underlying disease progression was documented or death occurred by any cause. The following variables were considered as confounders: recipient age, recipient sex, disease (myeloid or lymphoid), disease risk (standard or high), and donor type (MRD, MUD, or HAPLO donor). The percentage of participants progression free at 2 years is reported by donor type. Progression = > 25% increase of serum M-protein and/or urine M-protein. Also, an absolute increase in bone marrow plasma cells > 10%, new bone lesions or soft tissue plasmacytomas or increase in the size of existing bone lesions or soft tissue plasmacytomas or development of hypercalcemia that can be attributed solely to the plasma cell proliferative disorder.

    Measured: 2 years

  3. Overall Survival

    Estimate overall survival rates in participants treated with an alemtuzumab T cell depleted, reduced intensity preparative regimen followed by allogeneic hematopoietic transplantation. Disease-free survival (DFS), progression-free survival (PFS), and overall survival (OS) rates after SCT were estimated using the Kaplan-Meier method. We performed univariate comparisons by using the log-rank test. OS was defined as the period of time between the day of transplantation and death. The following variables were considered as confounders: recipient age, recipient sex, disease (myeloid or lymphoid), disease risk (standard or high), and donor type (MRD, MUD, or HAPLO donor). The percentage of participants surviving 2 years by donor type is reported.

    Measured: 2 years

  4. Graft Failure

    Estimate toxicity including graft-versus-host disease (GVHD) in participants treated with an alemtuzumab T cell depleted, reduced intensity preparative regimen followed by allogeneic hematopoietic transplantation. Bone marrow aspiration and/or biopsy were performed 3-5 weeks after transplant to assess donor-cell engraftment. Primary Graft Failure was defined as a neutrophil count below 500/μL or the absence of donor-derived hematopoiesis (<5%donor cells) before relapse, death, or re-transplantation. Secondary Graft Failure was defined as the achievement of primary engraftment and a subsequent decrease in neutrophils to 3 consecutive counts of less than 100/μL or the absence of donor-derived hematopoiesis (<5% donor cells) before relapse, death, or re-transplantation.

    Measured: 180 days

Timeline

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

  1. First posted18 Jan 2008 (estimated)
  2. Study startFeb 2008
  3. Primary completionJul 2013
  4. Study completionNov 2013

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
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
264 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00597714
Sponsor's protocol ID
Pro00003567
Status last verified
Feb 2014
First submitted
14 Jan 2008
Last updated
2 Jun 2014
Data monitoring committee
Yes

Publications

  • Kanda J, Long GD, Gasparetto C, Horwitz ME, Sullivan KM, Chute JP, Morris A, Shafique M, Li Z, Chao NJ, Rizzieri DA. Reduced-intensity allogeneic transplantation using alemtuzumab from HLA-matched related, unrelated, or haploidentical related donors for patients with hematologic malignancies. Biol Blood Marrow Transplant. 2014 Feb;20(2):257-63. doi: 10.1016/j.bbmt.2013.11.010. Epub 2013 Nov 20.

    PubMed 24269380

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Non-myeloablative Stem Cell Transplantation in people with Hodgkin's Disease and Non Hodgkin's Lymphoma, run by David Rizzieri, MD 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 2 Jun 2014. 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?

Yes. Results are posted in the registry (first posted 2 Jun 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Disease Free Survival (time frame: 2 years). 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 NCT00597714, 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 2 Jun 2014.

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