Clinical trial NCT02581007: Reduced Intensity Conditioning Transplant Using Haploidentical Donors
Official title: Reduced Intensity Conditioning and Transplantation of Partially HLA-Mismatched Peripheral Blood Stem Cells for Patients With Hematologic Malignancies
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
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
Lead sponsor: Northside Hospital, Inc.
Sponsor class: OTHER
Collaborators: name: Blood and Marrow Transplant Group of Georgia
First posted: 2015-10-20
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Detailed description: Patients will receive a haploidentical transpalnt using a fludarabine melphalan prepartive regimen. Patients will get cyclophosphamide on days 3 \& 4 post-transplant.

Eligibility criteria: Inclusion Criteria:

* 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:

  1. 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
  2. Acute Myelogenous Leukemia in first or greater remission
  3. 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
  4. 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
  5. Chronic Lymphocytic Leukemia/Prolymphocytic Leukemia: previously treated disease that has either relapsed or failed to respond adequately to conventional-dose therapy including purine analogs
  6. 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
  7. Myeloproliferative diseases (myelofibrosis, CMML)
  8. Multiple Myeloma with relapse after a prior autologous transplant or eligible for allogeneic HSCT based on other risk factors

Exclusion Criteria:

* 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

Primary outcomes:
measure: Graft Rejection
timeFrame: 100 days
Secondary outcomes:
measure: Overall Survival
timeFrame: 2 years
measure: Relapse Incidence
timeFrame: 2 years
measure: GVHD Incidence
timeFrame: 100 days
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Northside Hospital
state: Georgia
Study officials:
affiliation: Northside Hospital
name: Melhem Solh, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.