Total Body Irradiation/Fludarabine Based Ablative Haploidentical Transplant for Hematologic Diseases

NCT01336712 | Completed Phase 2 Results

• 1 other identifier: NSH 922
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

In this study, patients will receive a myeloablative preparative regimen consisting of fludarabine and total body irradiation (TBI), followed by a T cell replete, mobilized peripheral blood stem cell (PBSC) allograft from a partially matched related donor. All patients will receive post-transplant Cy in addition to standard post transplant immunosuppression with tacrolimus and MMF. The treatment protocol will be essentially identical to the prior study, with the exception of the substitution of TBI for Busulfan. The investigators hypothesize that this change will significantly reduce the risk of HC, while maintaining the efficacy of the transplant.

Conditions

Chronic Leukemia; Acute Leukemia; Hodgkin's Disease; Non-Hodgkin's Lymphoma; Myelodysplastic Syndrome

Keywords

CML; CLL; AML; ALL; MDS; HD; NHL; MFB; P.vera; Essential Thrombocytosis

Outcome Measures

Primary Outcomes (1)

• Percentage of Patients Experiencing Hemorrhagic Cystitis Post Transplant

  1.1 To estimate the incidence of BK virus-associated hemorrhagic cystitis following a TBI-based myeloablative haploidentical HSCT in patients with high risk hematologic malignancies.

  6 months

Secondary Outcomes (6)

• Survival

  2 year

• Percentage of Participatns With Donor Chimerism Post-transplant

  Day 30

• Disease Free Survival (DFS) Percentage

  2 year

• Non-relapsed Mortality (NRM) Percentage

  2 year

• Relapse Rate

  2 year

Study Arms (1)

Myeloablative Haploidentical Transplant

EXPERIMENTAL

Haplo transplant

Procedure: Peripheral Blood Stem Cell Transplant

Interventions

Peripheral Blood Stem Cell Transplant PROCEDURE

Total Body Irradiation 1200cGy (150cGy given in 8 fractions twice a day six hours apart on days -4, -3, -2 and -1. Fludarabine 30 mg/m\^2 given once a day for 3 days on days -7, -6 and -5 Cyclophosphamide 50mg/kg given one a day on days +3 and +4

Also known as: TBI, Fludara, Cytoxan

Myeloablative Haploidentical Transplant

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• No available matched related or unrelated donor OR a matched related or unrelated donor that is unavailable in the time frame necessary
• Availability of a 3/6 or 5/6 matched (HLA-A, B, DR) related donor
• Donor must have a negative HLA cross-match in the host vs. graft direction
• Donor must be willing to donate mobilized peripheral blood stem cells
• Age 18 to \</=60 years
• Karnofsky Status \>/= 70%
• Must have one of the following high-risk malignancies
• Chronic Myelogenous Leukemia (CML) in chronic phase, resistant and/or intolerant to TKI
• CML in accelerated phase
• CML blast crisis that has entered into 2nd Chronic phase following induction
• Acute Myelogenous Leukemia (AML) in 2nd or subsequent complete remission (CR)
• AML primary induction failure but subsequently in CR
• AML in 1st CR with poor risk cytogenetics or arising from preceding hematologic disease
• AML with marrow blasts \<5% but persistence of minimal residual disease by flow cytometry, cytogenetics or FISH
• Myelodysplastic Syndrome (MDS) that is treatment related

You may not qualify if:

• Patients will not be excluded on the basis of sex, racial or ethnic background
• Poor cardiac function: Left ventricular ejection fraction \< 45%
• Poor pulmonary function: FEV1 and FVD \< 60% predicted
• Poor liver function: bilirubin \>/= 2.5 mg/dl (not due to hemolysis, Gilbert's or primary malignancy), AST/ALT \> 3x ULN
• Poor renal function: Creatinine \>/= 2.0 mg/dl or creatinine clearance (calculated creatinine clearance is permitted) \< 40 mL/min based on Traditional Cockcroft-Gault formula: 140-age (yrs) x smaller of actual weight vs ideal body weight (kg)/72 x serum creatinine (mg/dl)
• HIV positive
• Women of childbearing potential who currently are pregnant or who are not practicing adequate contraception
• Patients who have any debilitating medical or psychiatric illness which would preclude their giving informed consent or their receiving optimal treatment and follow-up.
• Prior irradiation therapy rendering patient ineligible for TBI

Sponsors & Collaborators

• Northside Hospital, Inc.: lead
• Blood and Marrow Transplant Group of Georgia: collaborator

Study Sites (1)

Northside Hospital

Atlanta, Georgia, 30342, United States

Location

Related Publications (14)

• Szydlo R, Goldman JM, Klein JP, Gale RP, Ash RC, Bach FH, Bradley BA, Casper JT, Flomenberg N, Gajewski JL, Gluckman E, Henslee-Downey PJ, Hows JM, Jacobsen N, Kolb HJ, Lowenberg B, Masaoka T, Rowlings PA, Sondel PM, van Bekkum DW, van Rood JJ, Vowels MR, Zhang MJ, Horowitz MM. Results of allogeneic bone marrow transplants for leukemia using donors other than HLA-identical siblings. J Clin Oncol. 1997 May;15(5):1767-77. doi: 10.1200/JCO.1997.15.5.1767.

  PMID: 9164184 BACKGROUND

• Zuckerman T, Rowe JM. Alternative donor transplantation in acute myeloid leukemia: which source and when? Curr Opin Hematol. 2007 Mar;14(2):152-61. doi: 10.1097/MOH.0b013e328017f64d.

  PMID: 17255793 BACKGROUND

• Anasetti C, Amos D, Beatty PG, Appelbaum FR, Bensinger W, Buckner CD, Clift R, Doney K, Martin PJ, Mickelson E, et al. Effect of HLA compatibility on engraftment of bone marrow transplants in patients with leukemia or lymphoma. N Engl J Med. 1989 Jan 26;320(4):197-204. doi: 10.1056/NEJM198901263200401.

  PMID: 2643045 BACKGROUND

• Anasetti C, Beatty PG, Storb R, Martin PJ, Mori M, Sanders JE, Thomas ED, Hansen JA. Effect of HLA incompatibility on graft-versus-host disease, relapse, and survival after marrow transplantation for patients with leukemia or lymphoma. Hum Immunol. 1990 Oct;29(2):79-91. doi: 10.1016/0198-8859(90)90071-v.

  PMID: 2249952 BACKGROUND

• Kanda Y, Chiba S, Hirai H, Sakamaki H, Iseki T, Kodera Y, Karasuno T, Okamoto S, Hirabayashi N, Iwato K, Maruta A, Fujimori Y, Furukawa T, Mineishi S, Matsuo K, Hamajima N, Imamura M. Allogeneic hematopoietic stem cell transplantation from family members other than HLA-identical siblings over the last decade (1991-2000). Blood. 2003 Aug 15;102(4):1541-7. doi: 10.1182/blood-2003-02-0430. Epub 2003 Apr 24.

  PMID: 12714500 BACKGROUND

• Kernan NA, Flomenberg N, Dupont B, O'Reilly RJ. Graft rejection in recipients of T-cell-depleted HLA-nonidentical marrow transplants for leukemia. Identification of host-derived antidonor allocytotoxic T lymphocytes. Transplantation. 1987 Jun;43(6):842-7.

  PMID: 3296349 BACKGROUND

• Kernan NA, Collins NH, Juliano L, Cartagena T, Dupont B, O'Reilly RJ. Clonable T lymphocytes in T cell-depleted bone marrow transplants correlate with development of graft-v-host disease. Blood. 1986 Sep;68(3):770-3.

  PMID: 3527302 BACKGROUND

• Aversa F, Tabilio A, Velardi A, Cunningham I, Terenzi A, Falzetti F, Ruggeri L, Barbabietola G, Aristei C, Latini P, Reisner Y, Martelli MF. Treatment of high-risk acute leukemia with T-cell-depleted stem cells from related donors with one fully mismatched HLA haplotype. N Engl J Med. 1998 Oct 22;339(17):1186-93. doi: 10.1056/NEJM199810223391702.

  PMID: 9780338 BACKGROUND

• Mehta J, Singhal S, Gee AP, Chiang KY, Godder K, Rhee Fv Fv, DeRienzo S, O'Neal W, Lamb L, Henslee-Downey PJ. Bone marrow transplantation from partially HLA-mismatched family donors for acute leukemia: single-center experience of 201 patients. Bone Marrow Transplant. 2004 Feb;33(4):389-96. doi: 10.1038/sj.bmt.1704391.

  PMID: 14716338 BACKGROUND

• Aversa F, Terenzi A, Tabilio A, Falzetti F, Carotti A, Ballanti S, Felicini R, Falcinelli F, Velardi A, Ruggeri L, Aloisi T, Saab JP, Santucci A, Perruccio K, Martelli MP, Mecucci C, Reisner Y, Martelli MF. Full haplotype-mismatched hematopoietic stem-cell transplantation: a phase II study in patients with acute leukemia at high risk of relapse. J Clin Oncol. 2005 May 20;23(15):3447-54. doi: 10.1200/JCO.2005.09.117. Epub 2005 Mar 7.

  PMID: 15753458 BACKGROUND

• Lang P, Greil J, Bader P, Handgretinger R, Klingebiel T, Schumm M, Schlegel PG, Feuchtinger T, Pfeiffer M, Scheel-Walter H, Fuhrer M, Martin D, Niethammer D. Long-term outcome after haploidentical stem cell transplantation in children. Blood Cells Mol Dis. 2004 Nov-Dec;33(3):281-7. doi: 10.1016/j.bcmd.2004.08.017.

  PMID: 15528145 BACKGROUND

• Waller EK, Giver CR, Rosenthal H, Somani J, Langston AA, Lonial S, Roback JD, Li JM, Hossain MS, Redei I. Facilitating T-cell immune reconstitution after haploidentical transplantation in adults. Blood Cells Mol Dis. 2004 Nov-Dec;33(3):233-7. doi: 10.1016/j.bcmd.2004.08.009.

  PMID: 15528137 BACKGROUND

• Guinan EC, Boussiotis VA, Neuberg D, Brennan LL, Hirano N, Nadler LM, Gribben JG. Transplantation of anergic histoincompatible bone marrow allografts. N Engl J Med. 1999 Jun 3;340(22):1704-14. doi: 10.1056/NEJM199906033402202.

  PMID: 10352162 BACKGROUND

• Rizzieri DA, Koh LP, Long GD, Gasparetto C, Sullivan KM, Horwitz M, Chute J, Smith C, Gong JZ, Lagoo A, Niedzwiecki D, Dowell JM, Waters-Pick B, Liu C, Marshall D, Vredenburgh JJ, Gockerman J, Decastro C, Moore J, Chao NJ. Partially matched, nonmyeloablative allogeneic transplantation: clinical outcomes and immune reconstitution. J Clin Oncol. 2007 Feb 20;25(6):690-7. doi: 10.1200/JCO.2006.07.0953. Epub 2007 Jan 16.

  PMID: 17228020 BACKGROUND

MeSH Terms

Conditions

Hodgkin Disease; Lymphoma, Non-Hodgkin; Myelodysplastic Syndromes; Thrombocythemia, Essential

Interventions

Peripheral Blood Stem Cell Transplantation; fludarabine phosphate; Cyclophosphamide

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Bone Marrow Diseases; Hematologic Diseases; Blood Coagulation Disorders; Thrombocytosis; Blood Platelet Disorders; Myeloproliferative Disorders; Hemorrhagic Disorders

Intervention Hierarchy (Ancestors)

Hematopoietic Stem Cell Transplantation; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Results Point of Contact

• Title: Scott R. Solomon, MD (Principal Investigator)
• Organization: Blood and Marrow Transplant Group of Georgia

ssolomon@bmtga.com

404-255-1930

Study Officials

• Scott R Solomon, MD

  Blood and Marrow Transplant Group of Georgia

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• 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: SPONSOR

Study Record Dates

• First Submitted: April 14, 2011
• First Posted: April 18, 2011
• Study Start: April 1, 2011
• Primary Completion: December 1, 2014
• Study Completion: July 1, 2015
• Last Updated: January 14, 2016
• Results First Posted: January 14, 2016

Record last verified: 2015-12

Locations

US (1)