Allogeneic Transplantation Using Total Lymphoid Irradiation (TLI) and Anti-Thymocyte Globulin (ATG) for Older Patients With Hematologic Malignancies

NCT00185640 | Completed Phase 2 Results DMC FDA Drug

• 3 other identifiers: IRB-1196078998BMT153
• Study Type: interventional
• Target: 303
• Locations: 1 country
• Sites: 1

Brief Summary

To measure how frequently and to what degree a complication of transplant cell acute graft versus host disease (GvHD) occurs.

Conditions

Blood Cancer; Leukemia

Outcome Measures

Primary Outcomes (1)

• Acute Graft vs Host Disease (GvHD)

  The incidence of acute GvHD after transplantation was assessed per Glucksberg GvHD grade, a compound scale based on the following combinations of disease stages. Skin Stages * 0: No rash * 1: Maculopapular (MP) rash \<25% of body surface area * 2: MP rash on 25-50% of body surface area * 3: Generalized erythroderma (ED) * 4: Generalized ED with bullous formation and desquamation Liver Stages (Bilirubin in mg/dL) * 0: \<2 * 1: 2-3 * 2: 3.01-6 * 3: 6.01-15.0 * 4: \>15 Gastrointestinal (GI) Stages (diarrhea) * 0: None or \< 500 mL/day * 1: 500-999 mL/day * 2: 1000-1499 mL/day * 3: \>1500 mL/day * 4: Severe abdominal pain, with or without ileus Glucksberg Overall grade * Grade 1: Skin 1/2; GI 0; Liver 0; Karnofsky performance scale (KPS) 90-100% * Grade 2: Skin 1-3; GI 1; Liver 1; KPS 70-80 * Grade 2: Skin 2/3; GI 2/3; Liver 2-4; KPS 50-60 * Grade 4: Skin 2-4; GI 2-4; Liver 2-4; KPS 30-40

  100 days post-transplant

Secondary Outcomes (5)

• Acute Graft vs Host Disease (GvHD), All Evaluable

  100 days post-transplant

• Incidence of Relapse

  3 years

• Overall Survival (OS)

  3 and 5 years

• Event-free Survival (EFS)

  3 and 5 years

• Transplant-related Mortality

  1 year

Study Arms (1)

Non-myeloablative transplantation

EXPERIMENTAL

Pre-transplant total lymphoid irradiation (TLI) and anti-thymocyte globulin (ATG) infusion with Day 0 allogeneic hematopoietic cell transplant (HCT), followed by post-transplant immunosuppression by cyclosporine and mycophenolate mofetil.

Drug: Cyclosporine; Drug: Anti-thymocyte globulin (ATG); Drug: Mycophenolate mofetil (MMF); Drug: Filgrastim; Radiation: Total Lymphoid Irradiation (TLI)

Interventions

Cyclosporine DRUG

Starting day -3 at a dose of 5 mg/kg orally twice daily with a target trough level of 350 to 450 ng/mL

Also known as: Cyclosporin, Cyclosporin A

Non-myeloablative transplantation

Anti-thymocyte globulin (ATG) DRUG

1.5 mg/kg for total dose of 7.5mg/kg, IV starting on day -11 to day -7 before HCT

Also known as: Thymoglobulin

Non-myeloablative transplantation

Mycophenolate mofetil (MMF) DRUG

Begins on day 0 after HCT at a dose of 15 mg/kg. Transplant recipients who received related donor grafts received MMF twice daily and those who received unrelated donor grafts received MMF 3 times daily.

Also known as: CellCept

Non-myeloablative transplantation

Filgrastim DRUG

* Donors mobilized with 16 µg/kg/day filgrastim. * As needed, myelosuppression in transplant recipients will be managed with subcutaneous filgrastim 5 µg/kg/day

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

Non-myeloablative transplantation

Total Lymphoid Irradiation (TLI) RADIATION

0.8 Gy/day from day -11 to day -7 (inclusive) from day -4 to day -2 (inclusive) with 2 additional fractions of 0.8 Gy delivered on day -1 for total dose of 8 Gy.

Non-myeloablative transplantation

Eligibility Criteria

• Age: 50 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Any patient with one of the following hematolymphoid malignancies or syndromes in whom allogeneic hematopoietic stem cell transplant (HST) is warranted. Specific disease categories include:
• Indolent advanced stage non-Hodgkin lymphomas
• Mantle cell lymphoma
• Chronic lymphocytic leukemia
• Hodgkin disease (Hodgkin's lymphoma)
• Acute leukemias in complete remission
• Aplastic anemia
• Paroxysmal nocturnal hemoglobinuria
• Myelodysplastic or myeloproliferative syndromes.
• Other selected malignancies/disorders may also be considered but must be approved by the transplant team and the Principal Investigator.
• Age \> 50 years, or if \< 50 years of age, considered to be at high risk for regimen-related toxicity associated with conventional myeloablative transplants due to pre-existing medical conditions or prior therapy.
• A fully human leukocyte antigen (HLA)-identical sibling or matched unrelated donor is available. Potential participants with one antigen mismatched donors can be considered but only after discussion with the transplant team and the Principal Investigator.
• Participant must be competent to give consent.

You may not qualify if:

• Progressive hematolymphoid malignancies despite conventional therapies, or acute leukemias not in complete remission.
• Uncontrolled central nervous system (CNS) involvement with disease
• Fertile men or women unwilling to use contraceptive techniques during and for 12 months following treatment
• Pregnant
• Cardiac ejection fraction \< 30%
• Uncontrolled cardiac failure
• Pulmonary diffusing capacity (DLCO) \< 40% predicted
• Elevation of bilirubin to \> 3 mg/dL
• Transaminases \> 4 x the upper limit of normal
• Creatinine clearance \< 50 cc/min (24-hour urine collection)
• Karnofsky performance score \< 60%
• Poorly controlled hypertension on multiple antihypertensives
• Documented fungal disease that is progressive despite treatment
• HIV-positive. Other viral infections, ie, Hepatitis B- and C- positive, evaluated on a case-by-case basis
• Psychiatric disorders or psychosocial problems which in the opinion of the primary physician or Principal Investigator would place the patient at unacceptable risk from this regimen.

Sponsors & Collaborators

• Stanford University: lead

Study Sites (1)

Stanford University School of Medicine

Stanford, California, 94305, United States

Location

Related Publications (5)

• Lowsky R, Takahashi T, Liu YP, Dejbakhsh-Jones S, Grumet FC, Shizuru JA, Laport GG, Stockerl-Goldstein KE, Johnston LJ, Hoppe RT, Bloch DA, Blume KG, Negrin RS, Strober S. Protective conditioning for acute graft-versus-host disease. N Engl J Med. 2005 Sep 29;353(13):1321-31. doi: 10.1056/NEJMoa050642.

  PMID: 16192477 RESULT

• Jones CD, Arai S, Lowsky R, Tyan DB, Zehnder JL, Miklos DB. Complete donor T-cell engraftment 30 days after allogeneic transplantation predicts molecular remission in high-risk chronic lymphocytic leukaemia. Br J Haematol. 2010 Sep;150(5):637-9. doi: 10.1111/j.1365-2141.2010.08252.x. Epub 2010 Jun 7. No abstract available.

  PMID: 20528878 RESULT

• Rezvani AR, Kanate AS, Efron B, Chhabra S, Kohrt HE, Shizuru JA, Laport GG, Miklos DB, Benjamin JE, Johnston LJ, Arai S, Weng WK, Negrin RS, Strober S, Lowsky R. Allogeneic hematopoietic cell transplantation after failed autologous transplant for lymphoma using TLI and anti-thymocyte globulin conditioning. Bone Marrow Transplant. 2015 Oct;50(10):1286-92. doi: 10.1038/bmt.2015.149. Epub 2015 Jul 6.

  PMID: 26146806 RESULT

• Kohrt HE, Turnbull BB, Heydari K, Shizuru JA, Laport GG, Miklos DB, Johnston LJ, Arai S, Weng WK, Hoppe RT, Lavori PW, Blume KG, Negrin RS, Strober S, Lowsky R. TLI and ATG conditioning with low risk of graft-versus-host disease retains antitumor reactions after allogeneic hematopoietic cell transplantation from related and unrelated donors. Blood. 2009 Jul 30;114(5):1099-109. doi: 10.1182/blood-2009-03-211441. Epub 2009 May 7.

  PMID: 19423725 RESULT

• Benjamin J, Chhabra S, Kohrt HE, Lavori P, Laport GG, Arai S, Johnston L, Miklos DB, Shizuru JA, Weng WK, Negrin RS, Lowsky R. Total lymphoid irradiation-antithymocyte globulin conditioning and allogeneic transplantation for patients with myelodysplastic syndromes and myeloproliferative neoplasms. Biol Blood Marrow Transplant. 2014 Jun;20(6):837-43. doi: 10.1016/j.bbmt.2014.02.023. Epub 2014 Mar 7.

  PMID: 24607552 RESULT

MeSH Terms

Conditions

Hematologic Neoplasms; Leukemia

Interventions

Cyclosporine; Antilymphocyte Serum; thymoglobulin; Mycophenolic Acid; Filgrastim; Granulocyte Colony-Stimulating Factor

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins; Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures; Caproates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids; Lipids; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Biological Factors

Results Point of Contact

• Title: Robert Lowsky
• Organization: Stanford University

rlowsky@stanford.edu

650-723-0822

Study Officials

• Robert Lowsky

  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: Professor of Medicine

Study Record Dates

• First Submitted: September 12, 2005
• First Posted: September 16, 2005
• Study Start: March 1, 2003
• Primary Completion: April 1, 2014
• Study Completion: January 1, 2016
• Last Updated: June 29, 2021
• Results First Posted: October 3, 2017

Record last verified: 2021-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)