Reduced Intensity Conditioning Transplant Using Haploidentical Donors

NCT02581007 | Completed Phase 2 Results

• 1 other identifier: NSH 1132
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

This trial will evaluate the safety and efficacy of a reduced intensity allogeneic HSCT from partially HLA-mismatched first-degree relatives utilizing PBSC as the stem cell source. The primary objective of the study is to estimate the incidence of graft rejection and acute GVHD. A secondary objective will be to estimate the incidence of the relapse, NRM, OS, chronic GVHD and EFS.

Conditions

Chronic Myelogenous Leukemia; Acute Myelogenous Leukemia; Myelodysplastic Syndrome; Acute Lymphocytic Leukemia; Chronic Lymphocytic Leukemia; Hodgkin's Lymphoma; Non-Hodgkin's Lymphoma; Myelofibrosis; CMML; Multiple Myeloma

Keywords

CML; AML; MDS; ALL; CLL/CPL; HD; NHL; MPS; CMML; MM

Outcome Measures

Primary Outcomes (1)

• Graft Rejection

  Measurement of donor cells vs. recipient cells

  100 days

Secondary Outcomes (3)

• Overall Survival

  2 years

• Relapse Incidence

  2 years

• GVHD Incidence

  100 days

Study Arms (1)

Reduced-Intensity Mismatched Transplant

EXPERIMENTAL

Fludarabine, Melphalan \& Post-transplant cyclophosphamide

Drug: Fludarabine; Drug: Melphalan; Drug: Cyclophosphamide; Procedure: peripheral blood stem cell transplant

Interventions

Fludarabine DRUG

fludarabine (30mg/m2) given every day starting on Day -6 through Day -2;

Also known as: Fludara

Reduced-Intensity Mismatched Transplant

Melphalan DRUG

Also known as: melphalan (140mg/m2) given one time on Day -1.

Reduced-Intensity Mismatched Transplant

Cyclophosphamide DRUG

cyclophosphamide (50mg/kg) given every day starting on Day 3 through Day 4.

Also known as: Cytoxan

Reduced-Intensity Mismatched Transplant

peripheral blood stem cell transplant PROCEDURE

Also known as: HSCT

Reduced-Intensity Mismatched Transplant

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• No available matched related or unrelated donor, OR a matched related or unrelated donor will not be available in time frame necessary to perform potentially curative transplant
• Availability of 3/6 - 5/6 matched (HLA-A, B, DR) related donor (donor must have negative HLA cross-match in host vs. graft direction)
• Karnofsky status ≥70%
• One of the following high-risk malignancies:
• Chronic Myelogenous Leukemia: Chronic myelogenous leukemia in chronic phase, resistant or intolerant to available tyrosine kinase inhibitors; Chronic myelogenous leukemia in accelerated phase; Chronic myelogenous leukemia with blast crisis that has entered into a second chronic phase following induction chemotherapy
• Acute Myelogenous Leukemia in first or greater remission
• Myelodysplastic Syndrome at least one of the following: treatment-related; monosmy 7, complex cytogenetics or other high risk karyotype; IPSS score of 1.0 or greater; neutropenia or cytopenia requiring transfusion not responding to therapy; peripheral or BM blast count of \<10%; CMML
• Acute lymphocytic leukemia/lymphoblastic lymphoma: 2nd or subsequent complete remission; first complete remission; marrow blasts \<5%, but persistence of minimal residual disease by flow cytometry, cytogenetics, or FISH
• Chronic Lymphocytic Leukemia/Prolymphocytic Leukemia: previously treated disease that has either relapsed or failed to respond adequately to conventional-dose therapy including purine analogs
• Hodgkin's or Non-Hodgkin's Lymphoma (including low-grade, mantle cell, and intermediate-grade/diffuse): previously treated disease that has either relapsed or failed to respond adequately to conventional-dose therapy or autologous transplantation
• Myeloproliferative diseases (myelofibrosis, CMML)
• Multiple Myeloma with relapse after a prior autologous transplant or eligible for allogeneic HSCT based on other risk factors

You may not qualify if:

• not be excluded on basis of sex, racial, or ethnic backgrounds
• poor cardiac function: left ventricular ejection fraction \<40%
• poor pulmonary function: FEV1 and FVC \<50% predicted
• poor liver function: bilirubin \>2 mg/dl (not due to hemolysis, Gilbert's or primary malignancy)
• poor renal function: Creatinine \>2.0mg/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
• prior allogeneic transplant
• women of childbearing potential who currently are pregnant or who are not practicing adequate contraception
• any debilitating medical or psychiatric illness which would preclude their giving informed consent or their receiving optimal treatment and follow-up

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 (8)

• 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

• 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

• 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

• 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

• Bashey A, Solomon SR. T-cell replete haploidentical donor transplantation using post-transplant CY: an emerging standard-of-care option for patients who lack an HLA-identical sibling donor. Bone Marrow Transplant. 2014 Aug;49(8):999-1008. doi: 10.1038/bmt.2014.62. Epub 2014 May 19.

  PMID: 24842530 BACKGROUND

• O'Donnell PV, Luznik L, Jones RJ, Vogelsang GB, Leffell MS, Phelps M, Rhubart P, Cowan K, Piantados S, Fuchs EJ. Nonmyeloablative bone marrow transplantation from partially HLA-mismatched related donors using posttransplantation cyclophosphamide. Biol Blood Marrow Transplant. 2002;8(7):377-86. doi: 10.1053/bbmt.2002.v8.pm12171484.

  PMID: 12171484 BACKGROUND

• Solomon SR, Sizemore CA, Sanacore M, Zhang X, Brown S, Holland HK, Morris LE, Bashey A. Haploidentical transplantation using T cell replete peripheral blood stem cells and myeloablative conditioning in patients with high-risk hematologic malignancies who lack conventional donors is well tolerated and produces excellent relapse-free survival: results of a prospective phase II trial. Biol Blood Marrow Transplant. 2012 Dec;18(12):1859-66. doi: 10.1016/j.bbmt.2012.06.019. Epub 2012 Aug 1.

  PMID: 22863841 BACKGROUND

• Solomon SR, Sizemore CA, Sanacore M, Zhang X, Brown S, Holland HK, Morris LE, Bashey A. Total Body Irradiation-Based Myeloablative Haploidentical Stem Cell Transplantation Is a Safe and Effective Alternative to Unrelated Donor Transplantation in Patients Without Matched Sibling Donors. Biol Blood Marrow Transplant. 2015 Jul;21(7):1299-307. doi: 10.1016/j.bbmt.2015.03.003. Epub 2015 Mar 19.

  PMID: 25797174 BACKGROUND

MeSH Terms

Conditions

Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphocytic, Chronic, B-Cell; Hodgkin Disease; Lymphoma, Non-Hodgkin; Primary Myelofibrosis; Multiple Myeloma

Interventions

fludarabine; fludarabine phosphate; Melphalan; Cyclophosphamide; Peripheral Blood Stem Cell Transplantation

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, B-Cell; Lymphoma; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders

Intervention Hierarchy (Ancestors)

Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Phosphoramide Mustards; Phosphoramides; Organophosphorus Compounds; Hematopoietic Stem Cell Transplantation; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative

Results Point of Contact

• Title: Dr. Melhem Solh
• Organization: Northside Hospital

msolh@bmtga.com

404-255-1930

Study Officials

• Melhem Solh, MD

  Northside Hospital

  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: October 16, 2015
• First Posted: October 20, 2015
• Study Start: October 26, 2015
• Primary Completion: November 5, 2019
• Study Completion: December 28, 2020
• Last Updated: April 27, 2023
• Results First Posted: April 27, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)