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Mantle Cell LymphomaPhase 2273NCT01685606

Study of Infusion of Blood Cells (Lymphocytes) to Stimulate the Immune System to Fight Leukemia/Lymphoma

A Phase 2 study testing cellular immunotherapy in people with Mantle Cell Lymphoma and Diffuse Large Cell Lymphoma, run by Brown University at 2 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

The study of whether an infusion of blood cells called lymphocytes from a donor can stimulate the immune system to fight your leukemia/lymphoma. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
cellular immunotherapy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
6 participants
Where
2 sitesUnited States
Study dates
Mar 2013to Jun 2015
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

Who may be able to join

  • Histologic confirmation of hematological malignancy consisting of the following leukemias/lymphomas:
  • Mantle cell lymphoma with Ki-67>30%
  • Diffuse Large Cell Lymphoma
  • Burkitts Lymphoma
  • Systemic T Cell Lymphomas
  • Acute Myeloid Leukemia
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  • Acute Lymphoblastic Leukemia
  • Recurrence or progression of hematological malignancy after at least 1 prior standard treatment with progression within 6 months from last treatment.
  • No curative treatment option is available.
  • -> 4-weeks since prior chemotherapy or radiation to cellular therapy infusion. (Hydroxyurea may be utilized up to 48 hours prior to initiation of treatment on this protocol).
  • Age equal to or greater than 18 years.
  • Patients with a history of invasive second malignancy unless disease free for > 5 years.
  • Patients must have an expected life expectancy of at least 2 months at the time of initiation of treatment.
  • No active systemic infection.
  • Patients who have relapsed after standard autologous stem cell infusion are eligible as long as they meet all inclusion criteria and no exclusion criteria. These patients must be out more than 6 months from cell infusion to be eligible for enrollment.
  • DLCO > 40% with no symptomatic pulmonary disease.
  • LVEF > 40% by MUGA or echocardiogram.
  • Creatinine < 2.0 mg/dl. Total bilirubin less than 1.5x the upper limit of normal (ULN), AST < 3x ULN.
  • Non-pregnant and willing to use appropriate birth control during the duration of the study period.

Who cannot join

  • Evidence of HIV infection.
  • Any uncontrolled severe, concurrent illness which in the opinion of the treating physician would make this protocol treatment unreasonably hazardous for the patient.
  • Oxygen dependent obstructive pulmonary disease.
  • Failure to demonstrate adequate compliance with medical therapy and follow-up.
  • Significant medical or psychiatric illness that would impair the ability to participate in protocol therapy.
  • For women of reproductive potential, refusal to use effective form of contraception.
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  • Previous allogeneic stem cell transplant
  • Patients who have had previous purine analog (fludarabine, pentostatin, 2-CDA) -Patients with chronic myeloid leukemia (CML), chronic lymphocytic leukemia (CLL), multiple myeloma, and indolent lymphoma (follicular lymphoma, marginal zone lymphoma)
  • Patients with HLA antibodies to donor HLA type.

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Rhode Island Hospital

    Providence, Rhode Island, 02903

  • The Miriam Hospital

    Providence, Rhode Island, 02903

Other trials in United States

About this study

Official title: BrUOG 273:Cellular Immunotherapy For Refractory Hematological Malignancies:A Brown University Oncology Research Group Study

The study of whether an infusion of blood cells called lymphocytes from a donor can stimulate the immune system to fight your leukemia/lymphoma.

Read the detailed description

There have been important advances in the modulation of the immune system for the treatment of hematologic malignancies and solid tumors.

This protocol will build upon these previous observations as follows:

  • Haploidentical peripheral blood pheresed cells will be used at 1-2x108 CD3 cells/kg.
  • Total body radiation will not be utilized.
  • This modification may more effectively activate the recipient's immune system to attack their hematological malignancy by not damaging the recipient's immune cells prior to cellular infusion. Safety should be improved since the risk of graft versus host disease should be greatly reduced as the host's immune system will not be conditioned.
  • Granulocyte-colony stimulating factor (G-CSF) priming will not be used.
  • In our first clinical trial, G-CSF priming was not used for matched transplants. Our second trial did employ G-CSF priming in the haplo-identical setting. Previous data has cited a role for G-CSF in stimulation of invariant Natural Killer(NK) cells with enhanced GVL effects11. However, our most recent laboratory data with unprimed PBMC has shown effective cell kill activity without the addition of G-CSF. As G-CSF would be administered to healthy volunteers, the unclear benefit of the addition of this cytokine is offset by the potential side effects such as headache, fever, and bone pain. G-CSF mobilization serves to shift the response from a TH1 to TH2 through the increased production of T regulatory cells. The end result would be a decrease in immune stimulation. Since the goal of this study is to NOT have engraftment, the manipulation of the donor cells to dampen the host versus tumor stimulation is not needed nor desired. Furthermore, since this protocol is not a stem cell transplant, stem cells do not need to be mobilized with G-CSF.

It is important to note that the proposed study is not a stem cell transplant study. In the situation of stem cell transplants, the goal of the procedure is to have engraftment, or sustainable donor chimerism in the marrow to provide hematopoietic reconstitution as well as immunologic reconstitution. In this study, we are evaluating the use of donor lymphocytes (not stem cells) to stimulate an immune response of the recipients' immune system.

Being tested
cellular immunotherapy
Keywords
Leukemia, Lymphoma, Mantle cell, DLBCL, DLBC, Diffuse large B cell, T cell, AML, ALL
Medical subject headings
Lymphoma, Mantle-Cell, Lymphoma, Large B-Cell, Diffuse, Burkitt Lymphoma, Lymphoma, T-Cell, Leukemia, Myeloid, Acute, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Lymphoma

What participants receive

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

  • cellular immunotherapyBiological

    A minimum of 1x108 CD3+ cells and maximum of 2x108 CD3+ cells/kg from a haploidentical donor irrespective of the number of CD34+ cells will be infused.

Study groups in NCT01685606
Study groupRoleWhat they receive
cellular immunotherapyExperimentalA minimum of 1x108 CD3+ cells and maximum of 2x108 CD3+ cells/kg from a haploidentical donor will be infused, irrespective of the number of CD34+ cells.
Receives: Biological: cellular immunotherapy

What is being measured

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

  1. Overall Response Rate of Cellular Immune Therapy With HLA Haploidentical Peripheral Blood Pheresed Cells in Patients With Relapsed/Refractory Hematological Malignancies.

    Criteria for AML and ALL (adapted from Cheson et al.20)

    Complete remission (CR) is defined as the presence of all of the following

    • Peripheral blood
    • No leukemic blasts present.
    • No extramedullary findings of leukemia or disappearance of such (i.e. CNS or soft tissue involvement)
    • Bone marrow
    • Cellularity >20% with baseline maturation.
    • No Auer rods
    • Less than 5% blast cells.
    • Complete blood counts and bone marrow normalization criteria must be met within one week of each other. Hematopoeitic recovery is an ANC > 1.0 x 109/L and platelet count > 100x109/L. No specific hemoglobin or hematocrit level is specified but the patient must be transfusion free.

    Complete remission with incomplete recovery (CRi) is defined as the following:

    • Meets criteria for CR except
    • ANC < 1.0 x 109/L or platelet count < 100x109/L

    Partial remission (PR).

    • Must meet all criteria of a CR except that the bone marrow may contain 5-20% blasts.

    Measured: 8 weeks after infusion then 6 months after and every 4 months for approximately 2 years

Secondary outcomes (1)

  1. To Evaluate the Rate of Dose Limiting Toxicities of HLA Haploidentical Peripheral Blood Pheresed Cellular Infusions.

    Measured: 30 days and 16 weeks after infusion

Timeline

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

  1. First posted14 Sep 2012 (estimated)
  2. Study startMar 2013
  3. Primary completionJun 2015
  4. Study completionJun 2015

Why it stopped: Lack of accrual and low efficacy

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
6 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01685606
Sponsor's protocol ID
BrUOG 273
Acronym
273
Status last verified
Feb 2022
First submitted
12 Sep 2012
Last updated
4 Mar 2022
Data monitoring committee
Yes

Publications

  • Reagan JL, Fast LD, Safran H, Nevola M, Winer ES, Castillo JJ, Butera JN, Quesenberry MI, Young CT, Quesenberry PJ. Cellular immunotherapy for refractory hematological malignancies. J Transl Med. 2013 Jun 19;11:150. doi: 10.1186/1479-5876-11-150.

    PubMed 23782682

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing cellular immunotherapy in people with Mantle Cell Lymphoma and Diffuse Large Cell Lymphoma, run by Brown University 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 19 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: stopped early, as of the sponsor's last update on 4 Mar 2022. 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 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 26 Jun 2015). 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?

Overall Response Rate of Cellular Immune Therapy With HLA Haploidentical Peripheral Blood Pheresed Cells in Patients With Relapsed/Refractory Hematological Malignancies. (time frame: 8 weeks after infusion then 6 months after and every 4 months for approximately 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 NCT01685606, 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 Mar 2022.

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