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LymphomaPhase 1/2NCT02724904

Reduced Intensity Conditioning Allogeneic Hematopoietic Stem Cell Transplant (HSCT) For Lymphoma

A Phase 1/2 study testing Allogeneic stem cell transplantation, Fludarabine and Thiotepa in people with Lymphoma, run by Massachusetts General Hospital at 2 sites in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

This research study is assessing the feasibility of reduced intensity allogeneic hematopoietic stem cell transplantation (HSCT) as a possible treatment for relapsed / refractory non-Hodgkin lymphoma involving the central nervous system (CNS). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Lymphoma
What is being tested?
Allogeneic stem cell transplantation, Fludarabine and Thiotepa
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
2 sitesUnited States
Study dates
May 2017to Dec 2021
Phase
Phase 1/2
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 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Participants must have histologically or cytologically confirmed non-Hodgkin lymphoma involving the central nervous system (CNS) as defined by:
  • Biopsy of CNS mass in the brain, parenchyma, leptomeninges, or spinal cord demonstrating NHL.
  • Ocular biopsy from retina, subretinal pigment epithelial space, or optic nerve, or vitrectomy specimen, demonstrating NHL.
  • Biopsy of mass lesion outside of the CNS, or blood or body fluid specimen, documenting NHL, in conjunction with brain or spinal CT, PET/CT (positron emission tomography / computed tomography), or MRI showing radiographic abnormalities characteristic of CNS involvement with lymphoma.
  • CSF cytology demonstrating a malignant clonal NHL population, consistent with lymphomatous leptomeningitis, with or without a radiographically or pathologically identifiable CNS or systemic mass lesion. Patients with CSF (cerebral spinal fluid) studies negative for NHL by cytology but positive for a monoclonal population by flow cytometry and/or molecular PCR (polymerase chain reaction) studies may be eligible if they have radiographic evidence of a CNS lymphoma or if they have symptoms clinically consistent with CNS lymphomatous involvement; for such cases, please contact the protocol chair, Dr. Yi Bin Chen, to discuss eligibility prior to enrollment.
  • Patients must have experienced relapsed disease after high-dose chemotherapy with autologous stem cell transplantation (ASCT) OR have experienced relapse / progression on first-line high-dose methotrexate-based therapy and are not candidates for ASCT in the judgment of the treating physician. Discussion with the PI is encouraged for the latter scenario.
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  • All participants must demonstrate a partial or complete response (PR or CR) of their CNS and systemic disease to pre-enrollment therapy and must be in PR or CR at the time of enrollment. Acceptable therapies include systemic or intrathecal chemo/immunotherapy and/or radiotherapy as well as corticosteroids.
  • Age ≥ 18 years as this study will be open at sites which treat adults.
  • ECOG (Eastern Cooperative Oncology Group) performance status ≤ 2 (Karnofsky score ≥ 60%, see Appendix A).
  • Participants must have adequate organ function as defined below:
  • Total serum bilirubin within normal institutional limits (unless patient has Gilbert's syndrome, where then direct serum bilirubin should be within normal institutional limits).
  • AST (SGOT) / ALT(SGPT) ≤ 3× institutional upper limit of normal.
  • Serum creatinine within normal institutional limits
  • --- OR
  • Creatinine clearance ≥ 50 mL/min/1.73 m2 for participants with creatinine level above institutional normal.
  • Left ventricular ejection fraction ≥ 40% measured either by echocardiogram or nuclear cardiac scan.
  • FEV1 (forced expiratory volume in 1 second), FVC (forced vital capacity) and DLCO all ≥ 50% of predicted (DLCO corrected for hemoglobin).
  • Participants must have a well-matched adult donor willing to donate peripheral blood stem cells with well-matched defined as: 8/8 matched related or unrelated donor (HLA-A, B, C, DRB1 by allele level).
  • Because chemotherapy agents as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and for 12 months after the date of stem cell transplantation.
  • Ability to understand and the willingness to sign a written informed consent document.
  • Eligibility Criteria for Donors
  • Donors must be medically fit to donate peripheral blood stem cells through standard G-CSF mobilization as assessed by institutional or unrelated marrow registry standards.
  • Donors will not have to sign a study specific informed consent to participate given that donors will be undergoing standard G-CSF mobilization and leukapheresis.

Who cannot join

  • Participants who have had chemotherapy or radiotherapy within 4 weeks prior to the 1st day of conditioning chemotherapy.
  • Participants who are receiving any other investigational agents.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to fludarabine, thiotepa or other agents used in study.
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Pregnant or lactating women are excluded from this study because they are routinely ineligible to be treated with allogeneic stem cell transplantation.
  • HIV-positive participants on combination antiretroviral therapy are ineligible because of the potential for increased risk of lethal infections when treated with marrow-suppressive therapy.

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Massachusetts General Hospital

    Boston, Massachusetts, 02115

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02215

Other trials in United States

About this study

Official title: A Pilot Study of Reduced Intensity Conditioning Allogeneic Hematopoietic Stem Cell Transplantation for Patients With Relapsed CNS Involvement by Lymphoma

This research study is assessing the feasibility of reduced intensity allogeneic hematopoietic stem cell transplantation (HSCT) as a possible treatment for relapsed / refractory non-Hodgkin lymphoma involving the central nervous system (CNS). HSCT is the transplantation of stem cells, usually derived from bone marrow, peripheral blood, or umbilical cord blood.

Read the detailed description

This research study is a Pilot Study, which is the first time investigators are examining this study intervention (allogeneic stem cell transplantation) for this population (patients with CNS lymphoma), which is a type of stem cell transplantation.

Historically, patients with central nervous system (CNS) involvement by non-Hodgkin lymphoma (NHL) have had high rates of disease relapse after initial therapy. Given these poor outcomes with conventional chemotherapy, more intense treatment with high-dose chemotherapy and autologous stem cell transplantation (ASCT) has been explored, yet relapse remains an issue. For older patients, ASCT may not be feasible given the inability to tolerate high-doses of chemotherapy.

In patients with systemic NHL who relapse after ASCT or cannot tolerate ASCT, yet are responsive to chemotherapy, allogeneic stem cell transplant is often considered. Allogeneic transplantation is thought to work by giving the recipient an entirely new blood system from a donor. This new blood system includes a new immune system which can hopefully attack any lymphoma much like it would attack a bacterial or viral infection. Currently, this is one established standard of care for patients with lymphoma of the body who relapse after initial chemotherapy treatment. The investigators are testing if this treatment can be extended to patients with lymphoma of the central nervous system.

The following chemotherapy drugs included in this study which will be administered: Fludarabine, Thiotepa, and Methotrexate. The FDA (the U.S. Food and Drug Administration) has approved these chemotherapy agents individually as a treatment option for your disease. The combination has not been approved by the FDA. Thiotepa and Methotrexate have been shown to pass through the blood-brain barrier, a highly selective barrier that restricts many chemicals from entering the brain and spinal cord. Fludarabine is the backbone chemotherapy in all reduced intensity conditioning regimens.

Conditions
Lymphoma
Being tested
Allogeneic stem cell transplantation, Fludarabine, Thiotepa, Methotrexate
Keywords
Allogeneic hematopoietic stem cell transplantation, CNS Non-Hodgkin lymphoma
Medical subject headings
Lymphoma

What participants receive

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

  • Allogeneic stem cell transplantationProcedure or surgery

    Also called bone marrow transplant

    Reduced intensity allogeneic stem cell transplantation from a fully matched related or unrelated donor

  • FludarabineDrug

    Also called Fludara

    Standard Treatment

  • ThiotepaDrug

    Also called Thioplex

    Standard Treatment

  • MethotrexateDrug

    Also called Otrexup™

    IV Bolus

Study groups in NCT02724904
Study groupRoleWhat they receive
Allogeneic Stem Cell TransplantationExperimentalPatients will undergo reduced intensity conditioning (fludarabine and thiotepa) followed by fully matched related or unrelated allogeneic stem cell transplantation. Afterwards, patients will receive standard post-transplant care (Methotrexate).
Receives: Procedure: Allogeneic stem cell transplantation; Drug: Fludarabine; Drug: Thiotepa; Drug: Methotrexate

What is being measured

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

  1. Treatment-related mortality (TRM)

    Death from a non-relapse cause

    Measured: From date of transplant to 6 months afterwards

Secondary outcomes (3)

  1. Percentage of Participants that experienced grade II-IV acute graft-vs-host disease (GVHD)

    Cumulative incidence of acute GVHD

    Measured: From date of transplant to 6 months afterwards

  2. Progression-free survival (PFS)

    Relapse or death

    Measured: From date of transplant to disease progression or death, whichever occurred first, and patients who are alive without disease progression will be censored at last day known alive in the first 2 years after transplant

  3. Overall survival (OS)

    Death

    Measured: From time of transplant to death, or last day known alive in the first 2 years after transplant

Timeline

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

  1. First posted31 Mar 2016 (estimated)
  2. Study startMay 2017 (estimated)
  3. Primary completionDec 2019 (estimated)
  4. Study completionDec 2021 (estimated)

Why it stopped: Drug logistics

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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02724904
Sponsor's protocol ID
15-433
Status last verified
Mar 2017
First submitted
14 Jan 2016
Last updated
22 Mar 2017
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Allogeneic stem cell transplantation, Fludarabine and Thiotepa in people with Lymphoma, run by Massachusetts General Hospital 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 23 inclusion and 6 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: withdrawn, as of the sponsor's last update on 22 Mar 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 combined 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.

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 was withdrawn before enrolling participants, so there are no results.

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?

Treatment-related mortality (TRM) (time frame: From date of transplant to 6 months afterwards). 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 NCT02724904.

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 22 Mar 2017.

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