Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Engineered Donor Stem Cell Transplant in Treating Patients With Hematologic Malignancies

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02960646
Recruitment Status : Recruiting
First Posted : November 9, 2016
Last Update Posted : July 10, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Tracking Information
First Submitted Date  ICMJE November 8, 2016
First Posted Date  ICMJE November 9, 2016
Last Update Posted Date July 10, 2019
Actual Study Start Date  ICMJE January 18, 2017
Estimated Primary Completion Date February 28, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 8, 2019)
Incidence of treatment failure defined as primary graft failure, grade 3-4 acute graft versus host disease (aGVHD), or non-relapse mortality [ Time Frame: Up to 100 days ]
Original Primary Outcome Measures  ICMJE
 (submitted: November 8, 2016)
Safety of a Modified Peripheral Blood (PB) Graft for Haploidentical Transplantation [ Time Frame: 100 days after the transplant ]
For the purpose for safety monitoring, treatment failure defined as FAIL100 = [primary graft failure, grade 3-4 aGVHD, or non-relapse mortality within 100 days of transplant]. Safety monitoring method of Thall and Sung [47] used.
Change History Complete list of historical versions of study NCT02960646 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: July 8, 2019)
  • Immune reconstitution [ Time Frame: Up to 3 years ]
    Will be summarized by number of participants.
  • Incidence of infectious episodes [ Time Frame: Up to 3 years ]
    Will be summarized by number of participants.
  • Disease free survival (DFS) time [ Time Frame: Up to 3 years ]
    Will be estimated using the method of Kaplan and Meier.
  • Overall survival (OS) time [ Time Frame: Up to 3 years ]
    Will be estimated using the method of Kaplan and Meier.
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Engineered Donor Stem Cell Transplant in Treating Patients With Hematologic Malignancies
Official Title  ICMJE Phase I Clinical Trial Using an Engineered Peripheral Blood Graft for Haploidentical Transplantation
Brief Summary This pilot phase I trial studies the side effects of engineered donor stem cell transplant in treating patients with hematologic malignancies. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells (called graft-versus-host disease). Using T cells specially selected from donor blood in the laboratory for transplant may stop this from happening.
Detailed Description

PRIMARY OBJECTIVES:

I. To assess the safety of a modified peripheral blood (PB) graft for haploidentical transplantation, obtained by using depletion of naive, cluster of differentiation (CD)45RA+ T cells.

SECONDARY OBJECTIVES:

I. To estimate the proportion of patients with engraftment/graft failure. II. To determine the day 100 and 6 month non-relapse mortality (NRM). III. To estimate the cumulative incidence of grade 2-4 and 3-4 acute graft versus (vs.) host disease (aGVHD).

IV. To assess the rate of chronic GVHD within the first year post transplantation.

V. To assess immune reconstitution and the incidence of infectious episodes. VI. To assess disease response, disease-free survival (DFS) and overall survival (OS) after transplantation.

VII. To compare results with a retrospective cohort of patients treated with bone marrow graft on protocol 2009-0266.

OUTLINE:

Patients receive melphalan intravenously (IV) over 30 minutes on day -6 and fludarabine phosphate IV over 1 hour on days -6 to -3. Patients undergo total-body irradiation (TBI) on day -2 and CD45RA depleted peripheral blood stem cell transplantation on day 0. Patients also receive cyclophosphamide IV over 3 hours on days 3-4. Beginning on day 5, patients receive tacrolimus IV for 2 weeks and orally (PO) for at least 4 months. Beginning on day 7, patients receive filgrastim subcutaneously (SC) daily. Patients with CD20 positive lymphoma may receive rituximab IV on days -13, -6, 1, and 8.

After completion of study treatment, patients are followed up periodically.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome
  • Acute Myeloid Leukemia in Remission
  • Adult Acute Lymphoblastic Leukemia in Complete Remission
  • Aplastic Anemia
  • Blasts Under 10 Percent of Bone Marrow Nucleated Cells
  • Chronic Myelogenous Leukemia, BCR-ABL1 Positive
  • Chronic Myelomonocytic Leukemia
  • Hematopoietic Cell Transplantation Recipient
  • Minimal Residual Disease
  • Myeloproliferative Neoplasm
  • Plasma Cell Myeloma
  • Recurrent Chronic Lymphocytic Leukemia
  • Recurrent Hodgkin Lymphoma
  • Recurrent Non-Hodgkin Lymphoma
  • Recurrent Plasma Cell Myeloma
  • Recurrent Small Lymphocytic Lymphoma
  • Therapy-Related Myelodysplastic Syndrome
Intervention  ICMJE
  • Drug: Cyclophosphamide
    Given IV
    Other Names:
    • (-)-Cyclophosphamide
    • 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate
    • Carloxan
    • Ciclofosfamida
    • Ciclofosfamide
    • Cicloxal
    • Clafen
    • Claphene
    • CP monohydrate
    • CTX
    • CYCLO-cell
    • Cycloblastin
    • Cycloblastine
    • Cyclophospham
    • Cyclophosphamid monohydrate
    • Cyclophosphamidum
    • Cyclophosphan
    • Cyclophosphane
    • Cyclophosphanum
    • Cyclostin
    • Cyclostine
    • Cytophosphan
    • Cytophosphane
    • Cytoxan
    • Fosfaseron
    • Genoxal
    • Genuxal
    • Ledoxina
    • Mitoxan
    • Neosar
    • Revimmune
    • Syklofosfamid
    • WR- 138719
  • Biological: Filgrastim
    Given SC
    Other Names:
    • FILGRASTIM, LICENSE HOLDER UNSPECIFIED
    • G-CSF
    • Neupogen
    • r-metHuG-CSF
    • Recombinant Methionyl Human Granulocyte Colony Stimulating Factor
    • rG-CSF
    • Tevagrastim
  • Drug: Fludarabine Phosphate
    Given IV
    Other Names:
    • 2-F-ara-AMP
    • 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-
    • Beneflur
    • Fludara
    • SH T 586
  • Other: Laboratory Biomarker Analysis
    Correlative studies
  • Drug: Melphalan
    Given IV
    Other Names:
    • Alanine Nitrogen Mustard
    • CB-3025
    • L-PAM
    • L-Phenylalanine Mustard
    • L-sarcolysin
    • L-Sarcolysin Phenylalanine mustard
    • L-Sarcolysine
    • Melphalanum
    • Phenylalanine Mustard
    • Phenylalanine nitrogen mustard
    • Sarcoclorin
    • Sarkolysin
    • WR-19813
  • Procedure: Peripheral Blood Stem Cell Transplantation
    Undergo CD45RA depleted peripheral blood stem cell transplantation
    Other Names:
    • PBPC transplantation
    • PBSCT
    • Peripheral Blood Progenitor Cell Transplantation
    • Peripheral Stem Cell Support
    • Peripheral Stem Cell Transplant
    • Peripheral Stem Cell Transplantation
  • Biological: Rituximab
    Given IV
    Other Names:
    • ABP 798
    • BI 695500
    • C2B8 Monoclonal Antibody
    • Chimeric Anti-CD20 Antibody
    • CT-P10
    • IDEC-102
    • IDEC-C2B8
    • IDEC-C2B8 Monoclonal Antibody
    • MabThera
    • Monoclonal Antibody IDEC-C2B8
    • PF-05280586
    • Rituxan
    • Rituximab Biosimilar ABP 798
    • Rituximab Biosimilar BI 695500
    • Rituximab Biosimilar CT-P10
    • Rituximab Biosimilar GB241
    • Rituximab Biosimilar IBI301
    • Rituximab Biosimilar PF-05280586
    • Rituximab Biosimilar RTXM83
    • Rituximab Biosimilar SAIT101
    • RTXM83
  • Drug: Tacrolimus
    Given IV or PO
    Other Names:
    • FK 506
    • Fujimycin
    • Hecoria
    • Prograf
    • Protopic
  • Radiation: Total-Body Irradiation
    Undergo TBI
    Other Names:
    • Total Body Irradiation
    • Whole-Body Irradiation
Study Arms  ICMJE Experimental: Treatment (peripheral blood stem cell transplantation)
Patients receive melphalan IV over 30 minutes on day -6 and fludarabine phosphate IV over 1 hour on days -6 to -3. Patients undergo total-body irradiation (TBI) on day -2 and CD45RA depleted peripheral blood stem cell transplantation on day 0. Patients also receive cyclophosphamide IV over 3 hours on days 3-4. Beginning on day 5, patients receive tacrolimus IV for 2 weeks and PO for at least 4 months. Beginning on day 7, patients receive filgrastim SC daily. Patients with CD20 positive lymphoma may receive rituximab IV on days -13, -6, 1, and 8.
Interventions:
  • Drug: Cyclophosphamide
  • Biological: Filgrastim
  • Drug: Fludarabine Phosphate
  • Other: Laboratory Biomarker Analysis
  • Drug: Melphalan
  • Procedure: Peripheral Blood Stem Cell Transplantation
  • Biological: Rituximab
  • Drug: Tacrolimus
  • Radiation: Total-Body Irradiation
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: November 8, 2016)
12
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE February 28, 2020
Estimated Primary Completion Date February 28, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Lack of a human leukocyte antigen (HLA) matched related donor, lack of an immediately available 8/8 HLA matched unrelated donor
  • Patients must be diagnosed with a high-risk and/or advanced hematologic malignancy defined as one of the following
  • Acute lymphocytic leukemia (ALL) in complete remission (CR)1 with high-risk features including adverse cytogenetic such as t(9;22), t(1;19), t(4;11), or MLL gene rearrangements; in second or greater morphologic remission; persistent minimal residual disease
  • Acute myeloid leukemia (AML) in CR1 with intermediate-risk disease and persistent detectable minimal residual disease (MRD), or with high-risk features defined as: greater than 1 cycle of induction therapy required to achieve remission; preceding myelodysplastic syndrome (MDS) or myeloproliferative disease; presence of FLT3 mutations or internal tandem duplications, DNMT3a, TET2, MLL-partial tandem duplication (PTD), ASXL1, PHF6; FAB M6 or M7 classification; adverse cytogenetics including: -5, del 5q, -7, del7q, abnormalities involving 3q, 9q, 11q, 20q, 21q, 17, +8, complex (> 3 abnormalities)
  • Patients with AML must have less than 10% bone marrow blasts and < 100/mcL absolute peripheral blood blast count
  • Patients with AML in CR2, subsequent CR or with active disease at transplant (< 10% bone marrow blasts)
  • MDS with International Prognostic Scoring System (IPSS) intermediate-2 or higher, therapy-related MDS or chronic myelomonocytic leukemia (CMML)
  • Aplastic anemia with absolute neutrophil count (ANC) < 1,000 and transfusion dependent after failed immunosuppression therapy
  • Chronic myeloid leukemia (CML) >= 1st chronic phase, after failed >=2 lines of tyrosine kinase inhibitors; patients who progressed to blast phase must be in morphologic remission at transplant
  • Relapsed Hodgkin's disease or non-Hodgkin's lymphoma (NHL)
  • Patients with chemo-sensitive chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) with persistent or recurrent disease after fludarabine-based regimens with < 25% involvement by CLL/SLL cells
  • Patients with lymphoblastic lymphoma in remission or after partial response to chemotherapy
  • Patients with poor prognosis multiple myeloma by cytogenetics del13, del 17p, t(4;14) or t(14;16) or hypodiploidy, with advanced disease (stage >= 2) and /or relapsed after autologous stem cell transplant
  • Zubrod performance status 0-1 or Karnofsky performance status > 70%; patients > 50 years will have to have a Sorror Comorbidity Index =< 3
  • Available haploidentical donor willing and eligible to undergo a peripheral blood collection
  • Left ventricular ejection fraction (LVEF) > 40%
  • Bilirubin =< 1.5 mg/dl (unless Gilbert's syndrome), alanine aminotransferase (ALT) or aspartate aminotransferase (AST) =< 200 IU/ml for adults; conjugated (direct) bilirubin < 2 x upper limit of normal
  • Serum creatinine clearance >= 50 ml/min (calculated with Cockcroft-Gault formula)
  • Diffusing capacity for carbon monoxide (DLCO) >= 45% predicted corrected for hemoglobin
  • Patient or patient's legal representative must provide written informed consent

Exclusion Criteria:

  • Human immunodeficiency virus (HIV) positive; active hepatitis B or C
  • Patients with active infections; the principal investigator (PI) is the final arbiter of the eligibility
  • Liver cirrhosis with greater than grade 1 stage 1 inflammation/fibrosis
  • Uncontrolled central nervous system (CNS) involvement by tumor cells within the past 2 months
  • History of another primary malignancy that has not been in remission for at least 3 years; (the following are exempt from the 3-year limit: nonmelanoma skin cancer, fully excised melanoma in situ [stage 0], curatively treated localized prostate cancer, and cervical carcinoma in situ on biopsy or a squamous intraepithelial lesion on PAP smear)
  • Positive beta human chorionic gonadotropin (HCG) test in a woman with child bearing potential defined as not post-menopausal for 12 months or no previous surgical sterilization
  • Inability to comply with medical therapy or follow-up
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Stefan Ciurea 713-792-8750 sciurea@mdanderson.org
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02960646
Other Study ID Numbers  ICMJE 2014-0738
NCI-2016-01915 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2014-0738 ( Other Identifier: M D Anderson Cancer Center )
P30CA016672 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party M.D. Anderson Cancer Center
Study Sponsor  ICMJE M.D. Anderson Cancer Center
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Stefan O Ciurea M.D. Anderson Cancer Center
PRS Account M.D. Anderson Cancer Center
Verification Date July 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP