Autologous Followed by Non-myeloablative Allogeneic Transplantation for Non-Hodgkin's Lymphoma

NCT00481832 | Terminated Phase 2 Results DMC

• 3 other identifiers: IRB-0573097623BMT185
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this trial is to develop an alternative treatment for patients with poor risk non-Hodgkin's lymphoma. This trial uses a combination of high dose chemotherapy with stem cell transplant using the patient's own cells. This is followed with non-myeloablative transplant using stem cells from a related or unrelated donor to try and generate an anti-lymphoma response from the new immune system.

Conditions

Lymphoma, Non-Hodgkin

Outcome Measures

Primary Outcomes (1)

• Event-free Survival (EFS)

  Event-free survival (EFS) as determined for participants who receive both planned transplants, for a minimum of 3 years. Events are defined as "disease progression/relapse" and "death of all causes".

  3 years

Secondary Outcomes (9)

• Incidence of Chemotherapy-associated Pneumonitis

  3 years

• Relapse Rate

  3 years

• Overall Survival (OS)

  3 years

• Incidence of Acute Graft Versus Host Disease (GvHD)

  6 Months

• Incidence of Chronic Graft Versus Host Disease (GvHD)

  3 years

Study Arms (1)

T & B Cell Mobilization Auto & Allo HCT

EXPERIMENTAL

A transplant regimen that conditions the subjects using total lymphoid irradiation (TLI) and anti-thymocyte globulin(ATG) which will reduce acute graft-vs-host disease to negligible rates while maintaining the anti-tumor graft vs lymphoma GvL benefit. Along with TLI/ATG regiment; Solumedrol will be used as pre-medication and anti-emetic for any side effects. For stem cell mobilization, participants will be given either B Cell NLH or T Cell NHL. Before the filgrastim (G-CSF) mobilized PBPC infusion: acetaminophen, diphenhydramine and hydrocortisone will also be given as another set of pre-medications. BCNU, Etoposide, and Cyclophosphamide will be used as a preparative regimen. Cyclosporine and mycophenolate mofetil will be administered as an immunosuppressant after transplantation. Lastly, rituximab will be infused at the end of the transplantation regimen.

Drug: Cyclophosphamide; Drug: BCNU; Drug: Etoposide; Drug: Filgrastim; Drug: Antithymocyte globulin; Drug: Cyclosporine; Drug: Mycophenolate mofetil; Drug: Rituximab; Procedure: Autologous hematopoietic stem cell transplantation (auto-HSCT); Procedure: Allogeneic hematopoietic stem cell transplantation (allo-HSCT); Procedure: Total lymphoid irradiation; Drug: CD34+ Cells; Drug: Solu-Medrol

Interventions

Cyclophosphamide DRUG

4 gm /m² IV over 2 hours on day 8

Also known as: Cytoxan, Neosar

T & B Cell Mobilization Auto & Allo HCT

BCNU DRUG

The dose of BCNU will be based on actual body weight unless the actual body weight is more than 15 kg greater than the ideal body weight in which case the adjusted ideal body weight will be used: Males IBW = 50 kg + 2.3 kg/inch over 5 feet Females IBW = 45.5 kg + 2.3 kg/inch over 5 feet Adjusted IBW = IBW + 50% (actual weight - IBW)

Also known as: BiCNU, Carmustine

T & B Cell Mobilization Auto & Allo HCT

Etoposide DRUG

60mg/kg, IV over 4 hours on day -4 pre-transplant and for preparative regimen. The dose of etoposide for mobilization is 2 gm/ m².

Also known as: Eposin, Etopophos, VP-16

T & B Cell Mobilization Auto & Allo HCT

Filgrastim DRUG

10µg/kg sc qd starting day following cyclosphamide (or VP-16) until last day of apheresis

Also known as: Granulocyte colony-stimulating factor (G-CSF, GCSF), Colony-stimulating factor (CSF) 3

T & B Cell Mobilization Auto & Allo HCT

Antithymocyte globulin DRUG

1.5 mg/kg/d, IV from day -11 to -7

Also known as: ATG

T & B Cell Mobilization Auto & Allo HCT

Cyclosporine DRUG

5mg/kgbid,variable, po or IV

Also known as: cyclosporin, cyclosporin A

T & B Cell Mobilization Auto & Allo HCT

Mycophenolate mofetil DRUG

15 mg/kg po on day 0, at 5-10 hours after mobilized PBPC infusion is complete. Thereafter, beginning on day +1 MMF is taken at 15 mg/kg po b.i.d. (30 mg/kg/day) if transplantation was using a matched related donor and 15 mg/kg po t.i.d if from a matched unrelated donor or a one antigen mismatched donor. Doses will be rounded up to the nearest 250 mg (capsules are 250 mg). MMF will be stopped on day +28 for matched related donors. For one antigen mismatched related or unrelated donors, the taper will begin on day +40. MMF will be tapered by 10% weekly till off, typically by day +96. If there is nausea and vomiting at any time preventing the oral administration of MMF, MMF should be administered intravenously at an equal dose. MMF dosing is based on actual body weight.

Also known as: MMF, CellCep

T & B Cell Mobilization Auto & Allo HCT

Rituximab DRUG

375 mg/m2 IV (calculated based on actual body weight) on day 1 and day 7. Administered per current standard of care..

Also known as: Rituxan, MabThera

T & B Cell Mobilization Auto & Allo HCT

Autologous hematopoietic stem cell transplantation (auto-HSCT) PROCEDURE

Auto-HCT involves an intravenous infusion of a participant's previously collected and frozen white blood cells collected after treatment with mobilizing agents

Also known as: Autologous peripheral blood progenitor cell (PBPC) transplantation

T & B Cell Mobilization Auto & Allo HCT

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) PROCEDURE

Allo-HCT involves an intravenous infusion of a donor's white blood cells collected after treatment with mobilization with filgrastim (G-CSF)

Also known as: Allogeneic peripheral blood progenitor cell (PBPC) transplantation

T & B Cell Mobilization Auto & Allo HCT

Total lymphoid irradiation PROCEDURE

TLI is administered in 80cGy fractions on Days -11 to Day-7 relative to allo-HSCT

Also known as: TLI

T & B Cell Mobilization Auto & Allo HCT

CD34+ Cells DRUG

2 x 10e6 CD34+ cells per kg actual body weight on Day 0

T & B Cell Mobilization Auto & Allo HCT

Solu-Medrol DRUG

1 mg/kg, Day-11 to Day-7

Also known as: Methylprednisolone

T & B Cell Mobilization Auto & Allo HCT

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 to 70 years.
• Histologically proven non-Hodgkin's lymphoma
• Relapse after achieving initial remission or failure to achieve initial remission.
• KPS \> 70%
• Matched related or unrelated donor identified and available. Donor must be a complete match or have only a single allele mismatch.
• Recent Bone marrow biopsy and cytogenetic analysis
• Patients must have a pretreatment serum bilirubin \< 2 x the institutional ULN, a serum creatinine \< 2 x the institutional ULN and measured or estimated creatinine clearance \> 50 cc/min by the following formula (all tests must be performed within 28 days prior to mobilization ): Estimated Creatinine Clearance = (140 age) X WT(kg) X 0.85 if female 72 X serum creatinine(mg/dl).
• Patients must have an EKG within 42 days prior to registration that shows no significant abnormalities that are suggestive of active cardiac disease.
• Patients must have an echocardiogram or MUGA scan within 42 days of registration. If the ejection fraction is \< 40%, the patient will not be eligible. If the ejection fraction is 40-50%, patients must have an exercise echocardiogram or dobutamine-echo with a normal response to exercise.
• Patients must have a corrected diffusion capacity \> 50% prior to the autologous transplant and \> 40% prior to the allogeneic transplant.
• Patients with known allergy to etoposide or a history of Grade 3 hemorrhagic cystitis with cyclophosphamide are not eligible.
• Patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines.

You may not qualify if:

• Pregnant or breast-feeding women are ineligible due to the known birth defects association with the treatments used in this study.
• Patients known to be human immunodeficiency virus (HIV)-positive are ineligible because the concern for opportunistic infection and hematologic reserve are considered to be significantly greater in this population.
• Patients with prior maligancies diagnosed \> 5 years ago without evidence of disease are eligible. Patients with a prior malignancy treated \< 5 years ago but have a life expectancy of \> 5 years for that malignancy are eligible.
• Patients with uncontrolled infection.
• No prior autologous or allogeneic hematopoietic cell transplantation.
• Donor Selection/Evaluation:
• Related or unrelated HLA identical donors who are in good health and have no contra-indication to donation.
• No contra-indication for the donor to collection by apheresis of mononuclear cells mobilized by G-CSF at a dose of 16 µg/kg of body weight.
• Virology testing including CMV, HIV, EBV, HTLV, RPR, Hepatitis A, B and C will be performed within 30 days of donation.
• No prior malignancy is allowed except adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer or other cancer for which the donor has been disease-free for five years

Sponsors & Collaborators

• Stanford University: lead

Study Sites (1)

Stanford University School of Medicine

Stanford, California, 94305, United States

Location

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin

Interventions

Cyclophosphamide; Carmustine; Etoposide; etoposide phosphate; Filgrastim; Granulocyte Colony-Stimulating Factor; Colony-Stimulating Factors; Antilymphocyte Serum; Cyclosporine; Mycophenolic Acid; Rituximab; Transplantation; betibeglogene autotemcel; Methylprednisolone Hemisuccinate; Methylprednisolone

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Nitrosourea Compounds; Urea; Amides; Nitroso Compounds; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Glycoproteins; Glycoconjugates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures; Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Surgical Procedures, Operative; Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds

Results Point of Contact

• Title: Wen-Kai Weng, MD; Associate Professor of Medicine
• Organization: Stanford University School of Med

wkweng@stanford.edu

650-723-7689

Study Officials

• Wen-Kai Weng

  Stanford University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: May 31, 2007
• First Posted: June 4, 2007
• Study Start: January 1, 2007
• Primary Completion: October 27, 2014
• Study Completion: March 30, 2017
• Last Updated: February 14, 2018
• Results First Posted: February 14, 2018

Record last verified: 2018-01

Locations

US (1)