A Two-Step Approach to Reduced Intensity Bone Marrow Transplant for Patients With Hematological Malignancies

NCT01384513 | Completed Phase 2 Results DMC FDA Device

• 3 other identifiers: 11D.2472011-31JT 1795
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies how well reduced intensity donor stem cell transplant works in treating patients with hematologic malignancies. Giving chemotherapy and total-body irradiation before a donor peripheral blood stem cell transplant helps stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. The donated stem cells may also replace the patient's immune cells and help destroy any remaining cancer cells. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells (called graft-versus-host disease). Giving tacrolimus and mycophenolate mofetil after the transplant may stop this from happening. Once the donated stem cells begin working, the patient's immune system may see the remaining cancer cells as not belonging in the patient's body and destroy them. Giving an infusion of the donor's white blood cells (donor lymphocyte infusion) may boost this effect.

Conditions

Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Nasal Type Extranodal NK/T-cell Lymphoma; Aplastic Anemia; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Myeloid Leukemia in Remission; Childhood Myelodysplastic Syndromes; Chronic Eosinophilic Leukemia; Chronic Myelomonocytic Leukemia; Chronic Neutrophilic Leukemia; Essential Thrombocythemia; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Juvenile Myelomonocytic Leukemia; Mastocytosis; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Nodal Marginal Zone B-cell Lymphoma; Polycythemia Vera; Previously Treated Myelodysplastic Syndromes; Primary Myelofibrosis; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Recurrent/Refractory Childhood Hodgkin Lymphoma; Refractory Anemia; Refractory Anemia With Ringed Sideroblasts; Refractory Hairy Cell Leukemia; Refractory Multiple Myeloma; Secondary Myelodysplastic Syndromes; Splenic Marginal Zone Lymphoma; T-cell Large Granular Lymphocyte Leukemia; Waldenström Macroglobulinemia; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Lymphoblastic Leukemia in Remission

Keywords

Allogeneic HSCT; Hematopoietic stem cell transplantation

Outcome Measures

Primary Outcomes (1)

• Overall Survival (OS) in Patients With Haploidentical Family Donors With Hematological Malignancies in Morphological or Radiographic Remission or With Chemosensitive, Indolent Diseases

  The primary null hypothesis is that 2 year OS rate is at most 35%. This hypothesis will be rejected if the 95% confidence interval for year OS rate computed from the estimated Kaplan-Meier survival curves will be entirely above 0.35.

  At 2 years

Secondary Outcomes (7)

• Treatment Related Mortality (TRM)

  At 2 years

• Number of Participants With Acute G2-4 and/or Chronic Moderate or Severe GVHD

  Assessed up to 2 years

• Relapse Rate

  At 2 years

• Engraftment Rates

  44 weeks

• Incidence of Treatment Related Mortality (TRM)

  At 100 days

Study Arms (1)

Treatment (Allogeneic PBSCT)

EXPERIMENTAL

REDUCED INTENSITY CONDITIONING: Patients receive fludarabine phosphate IV over 60 minutes on days -11 to -8 and busulfan IV over 3 hours on days -10 to -9. Patients undergo TBI on day -6. Patients also receive cyclophosphamide IV over 2 hours on days -3 and -2. TRANSPLANTATION: Patients undergo DLI on day -6 and CD-34+ allogeneic PBSCT on day 0. GVHD PROPHYLAXIS: Beginning on day -1, patients receive tacrolimus IV or PO with taper beginning on day 42. Patients also receive mycophenolate mofetil IV BID on days -1 to 28.

Drug: Fludarabine; Drug: Busulfan; Radiation: Total Body Irradiation (TBI); Biological: Donor Lymphocyte Infusion (DLI); Drug: Cyclophosphamide (CY); Drug: Tacrolimus; Drug: Mycophenolate mofetil; Device: Allogeneic hematopoietic stem cell transplantation; Procedure: Peripheral blood stem cell transplantation (PBSCT)

Interventions

Fludarabine DRUG

Given IV

Also known as: fludarabine phosphate, Fludara

Treatment (Allogeneic PBSCT)

Busulfan DRUG

Given IV

Also known as: Myleran, Busulfex IV

Treatment (Allogeneic PBSCT)

Total Body Irradiation (TBI) RADIATION

2 Gy administered as part of the conditioning regimen

Also known as: radiotherapy

Treatment (Allogeneic PBSCT)

Donor Lymphocyte Infusion (DLI) BIOLOGICAL

Undergo DLI

Also known as: buffy coat fusion

Treatment (Allogeneic PBSCT)

Cyclophosphamide (CY) DRUG

Given IV

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

Treatment (Allogeneic PBSCT)

Tacrolimus DRUG

Given IV or PO

Also known as: FK-506, Fujimycin

Treatment (Allogeneic PBSCT)

Mycophenolate mofetil DRUG

Given IV

Also known as: MMF, CellCept

Treatment (Allogeneic PBSCT)

Allogeneic hematopoietic stem cell transplantation DEVICE

Undergo CD34+ allogeneic PBSCT

Also known as: CliniMACS

Treatment (Allogeneic PBSCT)

Peripheral blood stem cell transplantation (PBSCT) PROCEDURE

Undergo CD34+ allogeneic PBSCT

Also known as: PBPC transplantation, PBSC transplantation, peripheral blood progenitor cell transplantation, transplantation, peripheral blood stem cell

Treatment (Allogeneic PBSCT)

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 hematologic or oncologic diagnosis in which allogeneic HSCT is thought to be beneficial, and in whom front-line therapy has already been applied. Patients treated on this protocol will be without morphological evidence of disease (complete remission or "CR"), or if the patient has evidence of disease, the patient must have had at least a good partial response (PR) to the most recent therapy and the disease must be chemoresponsive.
• Patients treated on this study will have:
• Acute leukemia in 1st or 2nd CR
• MDS (myelodysplastic syndrome), specific subtypes of RA (refractory anemia) or RARS (refractory anemia with ringed sideroblasts) subtypes.
• Hodgkin or Indolent Non-Hodgkin's lymphoma with chemosensitive disease
• Myeloma without morphological evidence of disease, or a deep PR to the most recent therapy
• Myeloproliferative disorders with at least a PR to current therapy
• Aplastic Anemia
• A hematological or oncological disease (not listed) that meets the criteria reviewed above (in CR or with a good PR).
• Patients must have a related donor who is HLA mismatched at 2, 3, or 4 antigens at the HLA-A; B; C; DR loci in the GVHD direction. (Patients with related donors who are HLA identical or are a 1-antigen mismatch may be treated on this therapeutic approach, but will have their outcomes will not be part of the statistical aims of the study (see Summary section).
• Patients must adequate organ function:
• LVEF (Left ventricular end diastolic function) of \>50%
• DLCO (Diffusing Capacity of the Lung for Carbon Monoxide ) ≥50% of predicted corrected for hemoglobin
• 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

You may not qualify if:

• Human immunodeficiency virus (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 or anti-thymocyte globulin (ATG) within 8 weeks of the transplant admission; (documented by the absence of these agents in the medical record)
• Patients with evidence of another malignancy, exclusive of a skin cancer that requires only local treatment, should not be enrolled on this protocol

Sponsors & Collaborators

• Sidney Kimmel Comprehensive 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

Congenital Abnormalities; Lymphoma, Extranodal NK-T-Cell; Anemia, Aplastic; Pdgfra-Associated Chronic Eosinophilic Leukemia; Leukemia, Myelomonocytic, Chronic; Leukemia, Neutrophilic, Chronic; Thrombocythemia, Essential; Leukemia, Myelomonocytic, Juvenile; Mastocytosis; Myeloproliferative Disorders; Lymphoma, B-Cell, Marginal Zone; Polycythemia Vera; Primary Myelofibrosis; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myeloid, Acute; Lymphoma, Non-Hodgkin; Hodgkin Disease; Lymphoma, T-Cell, Cutaneous; Lymphoma, Follicular; Mycosis Fungoides; Sezary Syndrome; Leukemia, Lymphocytic, Chronic, B-Cell; Recurrence; Anemia, Refractory; Leukemia, Hairy Cell; Multiple Myeloma; Leukemia, Large Granular Lymphocytic; Waldenstrom Macroglobulinemia

Interventions

fludarabine; fludarabine phosphate; Busulfan; Whole-Body Irradiation; Radiotherapy; Cyclophosphamide; Tacrolimus; Mycophenolic Acid; Peripheral Blood Stem Cell Transplantation; Transplantation

Condition Hierarchy (Ancestors)

Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lymphoma, T-Cell; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Failure Disorders; Bone Marrow Diseases; Leukemia, Myeloid; Leukemia; Myelodysplastic-Myeloproliferative Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Blood Coagulation Disorders; Thrombocytosis; Blood Platelet Disorders; Hemorrhagic Disorders; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Mast Cell Activation Disorders; Immune System Diseases; Lymphoma, B-Cell; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Bone Marrow Neoplasms; Hematologic Neoplasms; Neoplasms by Site; Leukemia, Lymphoid; Leukemia, B-Cell; Myelodysplastic Syndromes; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Leukemia, T-Cell

Intervention Hierarchy (Ancestors)

Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Therapeutics; Investigative Techniques; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Macrolides; Lactones; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids; Hematopoietic Stem Cell Transplantation; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Surgical Procedures, Operative

Results Point of Contact

• Title: Dolores Grosso
• Organization: Tevogen Bio

dolores.grosso@tevogen.com

848-256-5751

Study Officials

• Usama Gergis, MD

  Sidney Kimmel Comprehensive Cancer Center at 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: June 27, 2011
• First Posted: June 29, 2011
• Study Start: August 4, 2011
• Primary Completion: November 13, 2020
• Study Completion: November 16, 2022
• Last Updated: April 15, 2026
• Results First Posted: April 15, 2026

Record last verified: 2026-03

Locations

US (1)