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

NCT02724904 | Withdrawn Phase 1 DMC FDA Drug

• 1 other identifier: 15-433
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 2

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.

Conditions

Lymphoma

Keywords

Allogeneic hematopoietic stem cell transplantation; CNS Non-Hodgkin lymphoma

Outcome Measures

Primary Outcomes (1)

• Treatment-related mortality (TRM)

  Death from a non-relapse cause

  From date of transplant to 6 months afterwards

Secondary Outcomes (3)

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

  From date of transplant to 6 months afterwards

• Progression-free survival (PFS)

  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

• Overall survival (OS)

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

Study Arms (1)

Allogeneic Stem Cell Transplantation

EXPERIMENTAL

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; Drug: Fludarabine; Drug: Thiotepa; Drug: Methotrexate

Interventions

Allogeneic stem cell transplantation PROCEDURE

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

Also known as: bone marrow transplant

Allogeneic Stem Cell Transplantation

Fludarabine DRUG

Standard Treatment

Also known as: Fludara

Allogeneic Stem Cell Transplantation

Thiotepa DRUG

Standard Treatment

Also known as: Thioplex

Allogeneic Stem Cell Transplantation

Methotrexate DRUG

IV Bolus

Also known as: Otrexup™

Allogeneic Stem Cell Transplantation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Adienne SA: collaborator
• Dana-Farber Cancer Institute: collaborator

Study Sites (2)

Massachusetts General Hospital

Boston, Massachusetts, 02115, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

MeSH Terms

Conditions

Lymphoma

Interventions

Bone Marrow Transplantation; fludarabine; fludarabine phosphate; Thiotepa; Methotrexate

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Tissue Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative; Phosphoramides; Organophosphorus Compounds; Organic Chemicals; Triethylenephosphoramide; Aziridines; Azirines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Yi-Bin Chen, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 14, 2016
• First Posted: March 31, 2016
• Study Start: May 1, 2017
• Primary Completion: December 1, 2019
• Study Completion: December 1, 2021
• Last Updated: March 22, 2017

Record last verified: 2017-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)