Bone Marrow Transplant Using a Reduced Intensity Regimen That is Given in Two Steps

NCT01350258 | Terminated Phase 1 Results DMC

• 3 other identifiers: 10D.5352010-40JT 2173
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

This is a research study involving the treatment of patients with hematological cancers with allogeneic (cells from a donor) hematopoietic stem cell transplant (HSCT). HSCT is often referred to as bone marrow transplant. Patients who are not expected to have long term survival after conventional therapy will undergo HSCT as a curative therapy after receiving front line therapy for their disease. This project is based on an HSCT approach that has been used at TJU since 2006 with the goal of optimizing this type of treatment further. In this new study, the investigators will substitute the chemotherapy agent, Melphalan (Mel), for cyclophosphamide (CY). Cyclophosphamide was used in the original trial. The research question is whether side effects are less using Mel and if donor T cells can be made tolerant to the recipient with the use of Mel. The proposed study is also more specific in terms of performance status and organ function entry criterion. The investigators observed in the original trial that patients with poor performance upon admission for transplant did not have as good outcomes. Because many older patients are treated according to this type of transplant, the chemotherapy and radiation used are less intensive than other types of transplant. The name for this in the transplant field is a reduced intensity hematopoietic stem cell transplant. The abbreviations most used in this document are RIC for reduced intensity conditioning, HSCT which refers to the transplant itself, and MEL which refers to the drug, Melphalan.

Conditions

Hematologic Malignancies; Acute Leukemia; Myelodysplastic Syndromes (MDS) Other Than RA or RARS Subtypes; Hodgkin's Lymphoma; Non-Hodgkin's Lymphoma; Myeloma; Chronic Myelogenous (or Myeloid) Leukemia (CML) Resistant to STI Therapy

Keywords

allogeneic HSCT; Hematopoietic stem cell transplantation

Outcome Measures

Primary Outcomes (2)

• Phase 1: Defined Dose of Melphalan (MEL)

  To define the dose of MEL required for the establishment of peripheral T cell tolerance with concomitant immune reconstitution.

  100 days post-transplant

• Phase 2: Non-Relapse Mortality (NRM)

  To evaluate the 100 day non-relapse mortality (NRM) rate in patients undergoing HSCT treated on this successor TJU 2 Step RIC haploidentical regimen and compare it with that of the initial regimen.

  100 days post-treatment

Secondary Outcomes (4)

• Relapse Rate

  At 1 and 3 years

• GVHD Incidence and Severity

  At 1 and 3 years

• Engraftment Rate and Lymphoid Reconstitution

  100 days post-transplant

• Overall Survival

  At 1 and 3 years

Study Arms (1)

Transplant Treatment Group

EXPERIMENTAL

All patients treated on this research study.

Drug: Fludarabine; Drug: Thiotepa; Radiation: Total Body Irradiation (TBI); Biological: Donor Lymphocyte Infusion (DLI); Drug: Melphalan; Device: Hematopoietic stem cell transplantation (HSCT)

Interventions

Fludarabine DRUG

Part of the conditioning regimen

Also known as: fludarabine phosphate, Fludara

Transplant Treatment Group

Thiotepa DRUG

Part of the conditioning regimen

Also known as: N,N'N'-triethylenethiophosphoramide

Transplant Treatment Group

Total Body Irradiation (TBI) RADIATION

There is one fraction of total body irradiation (2Gy) as part of the conditioning regimen.

Also known as: radiotherapy

Transplant Treatment Group

Donor Lymphocyte Infusion (DLI) BIOLOGICAL

Immediately following the conditioning regimen of fludarabine, thiotepa, and TBI, the patient receives a set dose of their donor's T cells (DLI), After the DLI, the donor's T cells will react with the remaining parts of the recipients immune system.

Also known as: buffy coat fusion

Transplant Treatment Group

Melphalan DRUG

Two days after the DLI, Melphalan will be given to eliminate the reacting T cells to avoid graft versus host disease. Non-activated T cells should not be affected by the Melphalan and remain to help fight infection.

Also known as: MEL, Melphalan hydrochloride, Alkeran

Transplant Treatment Group

Hematopoietic stem cell transplantation (HSCT) DEVICE

One day after the Melphalan ends, the patient will receive their donor's stem cells. This is the actual day of transplant. The CliniMACS® Plus Instrument will be used for the selection of human CD34+ hematopoietic stem and progenitor cells in human allogeneic hematopoietic stem cell transplantation.

Also known as: CliniMACS

Transplant Treatment Group

Eligibility Criteria

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

You may qualify if:

• Any patient with a high-risk hematologic or oncologic diagnosis in which allogeneic HSCT is thought to be beneficial, and in whom front-line therapy has already been applied. High risk is defined as:
• Acute leukemia in 3rd or greater CR or with persistent disease
• Myelodysplastic syndrome (MDS) other than RA or RARS subtypes.
• Hodgkin's or Non-Hodgkin's lymphoma in 3rd or greater remission or with persistent disease.
• Myeloma in 3rd or greater remission or with less than PR to most recent therapy.
• Chronic myelogenous (or myeloid) leukemia (CML) resistant to STI therapy
• Patients must have a related donor who is at least a 4 antigen match at the HLA-A; B; C; DR loci.
• Patients must adequate organ function:
• LVEF of \> or = 50%
• DLCO \> or = 50% of predicted corrected for hemoglobin
• Adequate liver function as defined by a serum bilirubin \< or = 1.8, AST or ALT \< or = 2.5X upper limit of normal
• GFR of \> or = 60 mL/min/1.73m2
• Performance status \> or = 80% (TJU Karnofsky) for patients \> or = 60 years old or \> or = 70% for patients \< 60.
• HCT-CI Score \< or = 4 points for patients \> or = 60 years old or \< or = 5 points for patients \< 60.
• Patients must be willing to use contraception if they have childbearing potential

You may not qualify if:

• Performance status \< 80% (TJU Karnofsky) for patients \> or = 60 years old or \< 70% for patients \< 60.
• HCT-CI Score \> 4 points for patients \> or = 60 years old or \> 5 points for patients \< 60.
• HIV positive
• Active involvement of the central nervous system with malignancy
• Inability to obtain informed consent
• Pregnancy
• Patients with life expectancy of \< 6 months for reasons other than their underlying hematologic/oncologic disorder
• Patients who have received alemtuzumab within 8 weeks of the transplant admission, or who have recently received horse or rabbit ant-thymocyte globulin and have an ATG level of \> or = 2 ugm/ml
• Patients with evidence of another malignancy, exclusive of a skin cancer that requires only local treatment, should not be enrolled on this protocol
• Donor Selection All donors are selected and screened for their ability to provide adequate infection-free apheresis products for the patient in a manner that does not put the donor at risk for negative consequences. Donor selection will be in compliance with 21 CFR 1271 and TJU BMT Program SOP CP: P009.03.

Sponsors & Collaborators

• Sidney Kimmel Cancer Center at Thomas Jefferson University: lead

Study Sites (1)

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

Related Links

• Kimmel Cancer Center at Thomas Jefferson University, an NCI-Designated Cancer Center
• Thomas Jefferson University Hospitals

MeSH Terms

Conditions

Hematologic Neoplasms; Myelodysplastic Syndromes; Hodgkin Disease; Lymphoma, Non-Hodgkin; Neoplasms, Plasma Cell; Leukemia

Interventions

fludarabine; fludarabine phosphate; Thiotepa; Whole-Body Irradiation; Radiotherapy; Melphalan; Hematopoietic Stem Cell Transplantation

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases; Lymphoma; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phosphoramides; Organophosphorus Compounds; Organic Chemicals; Triethylenephosphoramide; Aziridines; Azirines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Therapeutics; Investigative Techniques; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Transplantation; Surgical Procedures, Operative

Limitations and Caveats

Study was terminated due to extreme toxicity. The study was closed before any data could be collected.

Results Point of Contact

• Title: Dolores Grosso, CRNP, DNP
• Organization: Thomas Jefferson University

Dolores.Grosso@jefferson.edu

215-955-8874

Study Officials

• Dolores Grosso, DNP, CRNP

  Thomas Jefferson University

  PRINCIPAL INVESTIGATOR

• Neal Flomenberg, MD

  Thomas Jefferson University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 4, 2011
• First Posted: May 9, 2011
• Study Start: April 1, 2011
• Primary Completion: May 1, 2012
• Study Completion: August 1, 2012
• Last Updated: May 31, 2025
• Results First Posted: October 24, 2014

Record last verified: 2025-05

Locations

US (1)