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

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ClinicalTrials.gov Identifier: NCT02724904
Recruitment Status : Withdrawn (Drug logistics)
First Posted : March 31, 2016
Last Update Posted : March 22, 2017
Sponsor:
Collaborators:
Adienne SA
Dana-Farber Cancer Institute
Information provided by (Responsible Party):
Yi-Bin A. Chen, MD, Massachusetts General Hospital

Brief 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). HSCT is the transplantation of stem cells, usually derived from bone marrow, peripheral blood, or umbilical cord blood.

Condition or disease Intervention/treatment Phase
Lymphoma Procedure: Allogeneic stem cell transplantation Drug: Fludarabine Drug: Thiotepa Drug: Methotrexate Phase 1 Phase 2

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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Pilot Study of Reduced Intensity Conditioning Allogeneic Hematopoietic Stem Cell Transplantation for Patients With Relapsed CNS Involvement by Lymphoma
Estimated Study Start Date : May 2017
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : December 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

Arm Intervention/treatment
Experimental: Allogeneic Stem Cell Transplantation
Patients 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).
Procedure: Allogeneic stem cell transplantation
Reduced intensity allogeneic stem cell transplantation from a fully matched related or unrelated donor
Other Name: bone marrow transplant

Drug: Fludarabine
Standard Treatment
Other Name: Fludara

Drug: Thiotepa
Standard Treatment
Other Name: Thioplex

Drug: Methotrexate
IV Bolus
Other Name: Otrexup™




Primary Outcome Measures :
  1. Treatment-related mortality (TRM) [ Time Frame: From date of transplant to 6 months afterwards ]
    Death from a non-relapse cause


Secondary Outcome Measures :
  1. Percentage of Participants that experienced grade II-IV acute graft-vs-host disease (GVHD) [ Time Frame: From date of transplant to 6 months afterwards ]
    Cumulative incidence of acute GVHD

  2. Progression-free survival (PFS) [ Time Frame: 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 ]
    Relapse or death

  3. Overall survival (OS) [ Time Frame: From time of transplant to death, or last day known alive in the first 2 years after transplant ]
    Death



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.
  • 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.
  • Exclusion Criteria:
  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02724904


Locations
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United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02115
Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02215
Sponsors and Collaborators
Massachusetts General Hospital
Adienne SA
Dana-Farber Cancer Institute
Investigators
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Principal Investigator: Yi-Bin Chen, MD Massachusetts General Hospital

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Responsible Party: Yi-Bin A. Chen, MD, Principal Investigator, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT02724904     History of Changes
Other Study ID Numbers: 15-433
First Posted: March 31, 2016    Key Record Dates
Last Update Posted: March 22, 2017
Last Verified: March 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Yi-Bin A. Chen, MD, Massachusetts General Hospital:
Allogeneic hematopoietic stem cell transplantation
CNS Non-Hodgkin lymphoma
Additional relevant MeSH terms:
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Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Methotrexate
Fludarabine phosphate
Fludarabine
Thiotepa
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors
Antineoplastic Agents, Alkylating
Alkylating Agents
Myeloablative Agonists