A Two-Step Approach to Bone Marrow Transplant Using Cells From Two Partially-Matched Relatives

NCT01532635 | Terminated Phase 2 Results DMC

• 3 other identifiers: 11D.5702011-101JT 1832
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II clinical trial studies how well two donors stem cell transplant work in treating patients with high-risk hematologic malignancies. After receiving radiation to help further treat the disease, patients receive a dose of donors' T cells. T cells can fight infection and react against cancer cells. Two days after donors' T cells are given, patients receive cyclophosphamide (CY) to help destroy the most active T cells that may cause tissue damage (called graft versus host disease or GVHD). Some of the less reactive T cells are not destroyed by CY and they remain in the patient to help fight infection. A few days after the CY is given, patients receive donors' stem cells to help their blood counts recover. Using two donors' stem cell transplant instead of one donor may be more effective in treating patients with high-risk disease and may prevent the disease from coming back.

Conditions

Hematologic Malignancy; Leukemia; Acute Lymphoblastic Leukemia; ALL; Acute Myelogenous Leukemia; AML; Chronic Lymphocytic Leukemia; CLL; Lymphoma; Hodgkin's Lymphoma; Non-hodgkin's Lymphoma; Myeloma

Keywords

hematologic malignancy; leukemia; Acute lymphoblastic leukemia; ALL; Acute myelogenous leukemia; AML; Chronic lymphocytic leukemia; CLL; lymphoma; hodgkin's lymphoma; non-hodgkin's lymphoma; myeloma; allogeneic stem cell transplant; TJU 2-step; Hematopoietic stem cell transplant; HSCT; bone marrow transplant; Cyclophosphamide; MMF; Mycophenolate Mofetil

Outcome Measures

Primary Outcomes (1)

• One Year Relapse-Free Survival

  To assess one year relapse-free survival (RFS) in patients undergoing HSCT (hematopoietic stem cell transplantation) using the TJU 2 step-approach with two donors. Survival will be estimated by the Kaplan-Meier method. All estimates of rates will be presented with corresponding confidence intervals. For 1 year RFS rates, the method of Atkinson and Brown will be used to allow for the two-stage design; otherwise the method of Conover.

  1 year

Secondary Outcomes (8)

• Chimerism Assessment

  1 year

• Assessment of Dominance

  1 year

• Relapse Rates

  1 year

• Engraftment

  1 year

• Immune Reconstitution

  1 year

Study Arms (1)

Allogeneic HSCT Using Two Related Donors

EXPERIMENTAL

CONDITIONING: Patients undergo TBI BID on days -9 to -6, undergo DLI on day -6, and receive cyclophosphamide IV over 2 hours on days -3 and -2. TRANSPLANTATION: Patients undergo CD34+ selected allogeneic HSCT on day 0. GVHD PROPHYLAXIS: Patients receive tacrolimus IV or PO beginning on day -1 with taper beginning on day 42 and mycophenolate mofetil IV or PO BID on days -1 to 28.

Radiation: Total Body Irradiation (TBI); Biological: Donor Lymphocyte Infusion (DLI); Drug: Cyclophosphamide (CY); Drug: Tacrolimus; Drug: Mycophenolate Mofetil (MMF); Biological: Hematopoietic Stem Cell Transplant (HSCT)

Interventions

Total Body Irradiation (TBI) RADIATION

TBI twice daily for 4 days and occurs 6 to 9 days prior to the transplant. Total radiation dose is 12 Gy.

Also known as: TBI, radiotherapy

Allogeneic HSCT Using Two Related Donors

Donor Lymphocyte Infusion (DLI) BIOLOGICAL

DLI given 6 days prior to transplant (HSCT).

Also known as: DLI, T cell infusion

Allogeneic HSCT Using Two Related Donors

Cyclophosphamide (CY) DRUG

Cyclophosphamide given once daily at 60 mg/kg on days 2 and 3 prior to transplant (HSCT).

Also known as: CY, Endoxan, Cytoxan, Neosar, Procytox, Revimmune, cytophosphane

Allogeneic HSCT Using Two Related Donors

Tacrolimus DRUG

Tacrolimus is started the day before the transplant and stops a few months after transplant.

Also known as: FK-506, fujimycin, Prograf, Advagraf, Protopic

Allogeneic HSCT Using Two Related Donors

Mycophenolate Mofetil (MMF) DRUG

MMF is started the day before transplant and stops a few weeks after transplant.

Also known as: MMF, CellCept, Myfortic

Allogeneic HSCT Using Two Related Donors

Hematopoietic Stem Cell Transplant (HSCT) BIOLOGICAL

CD34+ selected Hematopoietic Stem Cell Transplant (HSCT) is performed using donor cells from two related donors. The CliniMACS® Plus Instrument will be used for the selection of human CD34+ hematopoietic stem cells.

Also known as: HSCT, stem cell transplant, CliniMACS

Allogeneic HSCT Using Two Related Donors

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 hematologic malignancy with residual disease (morphological, cytogenetic, molecular, or radiographic) after treatment with 1 or more chemotherapy regimens in whom achievement of remission with additional chemoradiotherapy is felt to be unlikely or who is in 3rd or greater CR. Patients with marrow based diseases in which the marrow biopsy does not meet criteria for active disease (i.e. \<5% blasts in acute leukemia) but who does not have full count recovery will be eligible for treatment on this high risk trial.
• Patients must have two related donors that meet an acceptable scenario as described above.
• Patients must adequate organ function:
• LVEF of \>= 50%
• DLCO (adjusted for hemoglobin) \>= 50% of predicted
• Adequate liver function as defined by a serum bilirubin =\< 1.8, AST or ALT \< 2.5X upper limit of normal
• Creatinine clearance of \>= 60 ml/min
• Karnofsky Performance Status of \> 80 % on the modified KPS tool (see Appendix A).
• Patients must be willing to use contraception if they have childbearing potential.
• Able to give informed consent

You may not qualify if:

• Modified KPS of \< 80%
• \>= 5 Comorbidity Points on the HCT-CI Index (See Appendix B)
• Class I or II antibodies against donor HLA antigens
• HIV positive
• Active involvement of the central nervous system with malignancy
• Psychiatric disorder that would preclude patients from signing an informed consent
• Pregnancy, or unwillingness to use contraception if they have child bearing potential
• Patients with life expectancy of =\< 6 months for reasons other than their underlying hematologic/oncologic disorder
• Alemtuzumab treatment within 8 weeks of HSCT admission.
• ATG level of \>= 2 ugm/ml
• Patients with active inflammatory processes (such as flair of an autoimmune disease) including T max \> 101, or active tissue inflammation are excluded.
• Inability to tolerate cyclophosphamide or undergo total body irradiation at the doses specified in the treatment plan.

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; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myeloid, Acute; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma; Hodgkin Disease; Lymphoma, Non-Hodgkin; Neoplasms, Plasma Cell

Interventions

Whole-Body Irradiation; Radiotherapy; Cyclophosphamide; Tacrolimus; Mycophenolic Acid; Stem Cell Transplantation

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Neoplasms by Histologic Type; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Myeloid; Leukemia, B-Cell; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Therapeutics; Investigative Techniques; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Macrolides; Lactones; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Transplantation; Surgical Procedures, Operative

Limitations and Caveats

Study was terminated due to poor accrual. No reportable data has been collected.

Results Point of Contact

• Title: Neal Flomenberg, MD
• Organization: Thomas Jefferson University

Neal.Flomenberg@jefferson.edu

215-955-8874

Study Officials

• Neal Flomenberg, MD

  Thomas Jefferson University

  PRINCIPAL INVESTIGATOR

• Dolores Grosso, DNP, CRNP

  Thomas Jefferson University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 6, 2012
• First Posted: February 14, 2012
• Study Start: March 1, 2012
• Primary Completion: February 1, 2013
• Study Completion: May 1, 2013
• Last Updated: May 4, 2025
• Results First Posted: November 10, 2014

Record last verified: 2025-05

Locations

US (1)