NCT00096460

Brief Summary

This study is designed as a Phase II/III, multi-center trial, comparing two transplant strategies to determine whether non-myeloablative allogeneic Hematopoietic Stem Cell Transplantation (HSCT) will improve long-term progression-free survival compared to autologous HSCT. Recipients will be biologically assigned to the appropriate treatment arm depending on the availability of a Human Leukocyte Antigen (HLA) matched sibling.

Trial Health

57
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
30

participants targeted

Target at P25-P50 for phase_2

Timeline
Completed

Started Aug 2004

Typical duration for phase_2

Geographic Reach
1 country

30 active sites

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

August 1, 2004

Completed
3 months until next milestone

First Submitted

Initial submission to the registry

November 9, 2004

Completed
1 day until next milestone

First Posted

Study publicly available on registry

November 10, 2004

Completed
1.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 1, 2006

Completed
3 years until next milestone

Study Completion

Last participant's last visit for all outcomes

March 1, 2009

Completed
3.6 years until next milestone

Results Posted

Study results publicly available

September 17, 2012

Completed
Last Updated

January 5, 2023

Status Verified

December 1, 2022

Enrollment Period

1.6 years

First QC Date

November 9, 2004

Results QC Date

August 16, 2011

Last Update Submit

December 7, 2022

Conditions

Outcome Measures

Primary Outcomes (1)

  • Lymphoma Progression-free Survival

    Three years post-Hematopoietic Stem Cell Transplant (HSCT)

Study Arms (2)

Autologous Transplant

ACTIVE COMPARATOR

Cyclophosphamide and Rituximab with Filgrastim conditioning and chemotherapy or radiation therapy prior to autologous Hematopoietic Stem Cell Transplant (HSCT). Rituximab maintenance therapy following HSCT.

Drug: Cyclophosphamide and RituximabDrug: FilgrastimRadiation: Chemotherapy or Radiation therapyProcedure: Autologous transplantDrug: Rituximab maintenance therapy

Allogeneic Transplant

ACTIVE COMPARATOR

Non-myeloablative conditioning regimen followed by allogeneic Hematopoietic Stem Cell Transplant (HSCT). Graft-versus-Host Disease (GVHD) Prophylaxis therapy following HSCT.

Drug: Cyclophosphamide and RituximabDrug: FilgrastimDrug: Non-myeloablative Conditioning regimenProcedure: Allogeneic transplantDrug: GVHD Prophylaxis

Interventions

Prior to undergoing HSCT, all patients will receive Cyclophosphamide 4 gm/m2 with Rituximab 375 mg/m2 x 2 doses and G-CSF support.

Also known as: Cytoxan® and Rituxan
Allogeneic TransplantAutologous Transplant

Autologous HSCT patients will receive 10 mcg/kg/day and allogeneic HSCT patients will receive 5 mcg/kg/day subcutaneous (SQ) or intravenous (IV) starting 2 days after the initiation of Cyclophosphamide.

Also known as: G-CSF
Allogeneic TransplantAutologous Transplant

Chemotherapy - BCNU 15 mg/kg IV x 1 dose to be administered over 2 hours on Day -6 pre-HSCT. VP-16 60 mg/kg IV x 1 dose to be administered over 4 hours on Day -4. Radiation - administered at a rate of \< 20 cGy/min in one of the following doses; 120 cGy/fraction are administered at no less than 4-hour intervals three times/day or 2 times/day for a total of 10 doses (1200 cGy) over 4 days (Day -8, -7, -6 and -5), or doses of 150 cGy/fraction twice daily for a total of 8 doses (1200 cGy) over 4 days (Day -8, -7, -6 and -5). VP-16 60 mg/kg IV x 1 dose to be administered over 4 hours on Day -4 pre-HSCT. Cyclophosphamide 100 mg/kg IV x 1 dose to be administered over 2 hours on Day -2 pre-HSCT. G-CSF 5 mcg/kg SQ or IV to start on Day +5 post-HSCT and continue until ANC \> 500/mm3 x 3 days.

Also known as: Etoposide and Carmustine, BCNU and VP-16
Autologous Transplant

Fludarabine 30 mg/m2 IV x 3 doses total to be administered daily over 30 minutes on Days -6, -5 and -4 pre-HSCT. Cyclophosphamide 750 mg/m IV x 3 doses total to be administered daily over 1 hour on Days -6, -5 and -4 pre-HSCT. Administer cyclophosphamide approximately 4 hours after start of fludarabine infusion. Rituximab 375 mg/m2 IV x 4 doses total to be administered on Days -13 and -6 pre HSCT and Days +1 and +8 post HSCT.

Also known as: Fludarabine, Cyclophosphamide, and Rituximab, Fludara, Cytoxan®, and Rituxan
Allogeneic Transplant

Infusion of G-CSF mobilized allogeneic hematopoietic stem cells

Also known as: HSCT
Allogeneic Transplant

Infusion of G-CSF mobilized autologous hematopoietic stem cells

Also known as: HSCT
Autologous Transplant

Patients must have sufficiently recovered from autologous HSCT in order to receive rituximab maintenance therapy as specified below: Dose #1: Day +42 post-autologous HSCT Dose #2: Day +49 post-autologous HSCT Dose #3: Day +56 post-autologous HSCT Dose #4: Day +63 post-autologous HSCT

Also known as: Rituxan
Autologous Transplant

Tacrolimus 0.09 mg/kg/day PO, based on body weight formulas will start on Day -2 and continue until Day +90 post-HSCT. Tacrolimus (or cyclosporine, if applicable) will be given orally in a twice-daily divided dose. Methotrexate 5 mg/m2 Intravenous Pyelogram (IVP) will be administered on Days +1, +3 and +6 post-HSCT.

Also known as: Tacrolimus and Methotrexate, Prograf® and MTX
Allogeneic Transplant

Eligibility Criteria

AgeUp to 75 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • Histologically confirmed recurrent Revised European American Lymphoma (REAL) classification follicle center lymphoma, follicular grades I and II, OR histologically confirmed World Health Organization (WHO) classification follicular lymphoma grades 1, 2, 3a or 3b; for either classification, the diffuse component or presence of large cleaved cells (if present) cannot be more than 50% of high power field; patients do not have to express t(14;18) to be eligible
  • Received three or fewer prior regimens of chemotherapy; monoclonal antibody therapy and involved field radiation therapy will not be counted as a prior therapy
  • Beyond first Complete Remission (CR) or first Partial Remission (PR) AND demonstrate chemosensitive disease; chemosensitive disease will be defined as less than 20% bone marrow involvement in the aspirate or core biopsy with follicular lymphoma AND lymph node size in axial diameter of less than 3 cm or a greater than 50% reduction in estimated lymph node volume to be measured as product of bi-dimensional measurements; Positron Emission Tomography (PET) scanning will not be used for staging or response purposes
  • Patients with adequate organ function as measured by:
  • Cardiac: left ventricular ejection fraction at rest at least 45%
  • Hepatic: bilirubin less than 2 times the upper limit of normal and alanine transaminase (ALT) and aspartate aminotransferase (AST) less than 3 times the upper limit of normal
  • Renal: creatinine clearance greater than 40 mL/min
  • Pulmonary: Diffusing capacity of the lung for carbon monoxide (DLCO), Forced expiratory volume in one second (FEV1), and Forced vital capacity (FVC) greater than 50% of predicted (corrected for hemoglobin)
  • If the patient is younger than 18 years of age and they have reached the age of assent, then they must have completed the local Institutional Review Board (IRB) assent process.
  • Able to receive cyclophosphamide and rituximab mobilization chemotherapy no earlier than 3 weeks from the beginning of the most recent cycle of salvage chemotherapy and no later than 6 weeks from enrollment
  • Collection of an autologous or allogeneic graft of at least 2.0 \* 10\^6 CD34+ cells/kg
  • Blood count recovery defined as Absolute Neutrophil Count (ANC) greater than 1000/mm3 and platelets greater than 100 \* 10\^9/L
  • Off intravenous antibiotics and off amphotericin B formulations for proven, probable or possible fungal infections
  • No active Cytomegalovirus (CMV) infections or for patients with CMV infection post-autograft, treated with ganciclovir, valganciclovir, or foscarnet per institutional guidelines and CMV antigenemia negative
  • Mucositis resolved and off hyperalimentation

You may not qualify if:

  • Karnofsky performance score less than 70%
  • Follicular lymphoma that show histologic evidence of transformation
  • Uncontrolled hypertension
  • Patients with uncontrolled bacterial, viral or fungal infection (currently taking medication and progression without clinical improvement).
  • Prior malignancies except resected basal cell carcinoma or treated cervical carcinoma in situ; cancer treated with curative intent more than 5 years previously will be reviewed on a case-by-case basis by a Protocol Chair or Medical Monitor.
  • Pregnant (positive Beta Human chorionic gonadotropin (β-HCG)) or breastfeeding
  • Seropositive for Human immunodeficiency virus (HIV)
  • Unwilling to use contraceptive techniques during treatment
  • Prior autologous or allogeneic HSCT
  • Known anaphylactic reaction to rituximab

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (30)

City of Hope National Medical Center

Duarte, California, 91010-3000, United States

Location

Scripps Clinic

La Jolla, California, 92037, United States

Location

UCSD Medical Center

La Jolla, California, 92093, United States

Location

Stanford Hospital and Clinics

Stanford, California, 94305, United States

Location

University of Florida College of Medicine (Shands)

Gainesville, Florida, 32610-0277, United States

Location

H. Lee Moffitt Cancer Center

Tampa, Florida, 33624, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

BMT Group of Georgia

Atlanta, Georgia, 30342, United States

Location

Loyola University

Atlanta, Georgia, 60153, United States

Location

Indiana BMT at Beech Grove

Beech Grove, Indiana, 46107, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

University of Michigan Medical Center

Ann Arbor, Michigan, 48105-2967, United States

Location

Karmanos Cancer Institute/BMT

Detroit, Michigan, 48201, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Kansas City Cancer Centers

Kansas City, Missouri, 64111, United States

Location

Washington University/Barnes Jewish Hospital

St Louis, Missouri, 63110, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198-7680, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Duke University Medical Center

Durham, North Carolina, 27705, United States

Location

University Hospitals of Cleveland/Case Western

Cleveland, Ohio, 44106-5061, United States

Location

Providence Portland Medical Center

Portland, Oregon, 97213, United States

Location

Oregon Health Sciences University

Portland, Oregon, 97239-3098, United States

Location

University of Pennsylvania Cancer Center

Philadelphia, Pennsylvania, 19104, United States

Location

University of Pittsburgh Cancer Institute

Pittsburgh, Pennsylvania, 15232, United States

Location

Vanderbilt University

Nashville, Tennessee, 37232-8210, United States

Location

Baylor University Medical Center

Dallas, Texas, 75246, United States

Location

University of Texas/MD Anderson CRC

Houston, Texas, 77030, United States

Location

Virginia Commonwealth University MCV Hospitals

Richmond, Virginia, 23298, United States

Location

University of Wisconsin Hospital and Clinics

Madison, Wisconsin, 53792-5156, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53211, United States

Location

Related Publications (1)

  • Tomblyn MR, Ewell M, Bredeson C, Kahl BS, Goodman SA, Horowitz MM, Vose JM, Negrin RS, Laport GG. Autologous versus reduced-intensity allogeneic hematopoietic cell transplantation for patients with chemosensitive follicular non-Hodgkin lymphoma beyond first complete response or first partial response. Biol Blood Marrow Transplant. 2011 Jul;17(7):1051-7. doi: 10.1016/j.bbmt.2010.11.004. Epub 2010 Nov 10.

MeSH Terms

Conditions

Lymphoma, Follicular

Interventions

CyclophosphamideRituximabFilgrastimGranulocyte Colony-Stimulating FactorDrug TherapyRadiotherapyEtoposideCarmustinefludarabinefludarabine phosphateTransplantation, HomologousTransplantation, AutologousTacrolimusMethotrexate

Condition Hierarchy (Ancestors)

Lymphoma, Non-HodgkinLymphomaNeoplasms by Histologic TypeNeoplasmsLymphoproliferative DisordersLymphatic DiseasesHemic and Lymphatic DiseasesImmunoproliferative DisordersImmune System Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide MustardsNitrogen Mustard CompoundsMustard CompoundsHydrocarbons, HalogenatedHydrocarbonsOrganic ChemicalsPhosphoramidesOrganophosphorus CompoundsAntibodies, Monoclonal, Murine-DerivedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulinsColony-Stimulating FactorsGlycoproteinsGlycoconjugatesCarbohydratesHematopoietic Cell Growth FactorsCytokinesIntercellular Signaling Peptides and ProteinsPeptidesBiological FactorsTherapeuticsPodophyllotoxinTetrahydronaphthalenesNaphthalenesPolycyclic Aromatic HydrocarbonsHydrocarbons, AromaticHydrocarbons, CyclicPolycyclic CompoundsGlucosidesGlycosidesNitrosourea CompoundsUreaAmidesNitroso CompoundsTransplantationSurgical Procedures, OperativeMacrolidesLactonesAminopterinPterinsPteridinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic Compounds

Results Point of Contact

Title
Adam Mendizabal, PhD
Organization
The EMMES Corporation

Study Officials

  • Mary Horowitz, MD

    Center for International Blood and Marrow Transplant Research

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

November 9, 2004

First Posted

November 10, 2004

Study Start

August 1, 2004

Primary Completion

March 1, 2006

Study Completion

March 1, 2009

Last Updated

January 5, 2023

Results First Posted

September 17, 2012

Record last verified: 2022-12

Data Sharing

IPD Sharing
Will share

Locations