Engineered Donor Stem Cell Transplant in Treating Patients With Hematologic Malignancies

• Register: ClinicalTrials.gov
• Last refreshed on: 27 February 2023
• Main ID: NCT02960646
• Date of registration: 08/11/2016
• Prospective Registration: Yes
• Primary sponsor: M.D. Anderson Cancer Center
• Public title: Engineered Donor Stem Cell Transplant in Treating Patients With Hematologic Malignancies
• Scientific title: Phase I Clinical Trial Using an Engineered Peripheral Blood Graft for Haploidentical Transplantation
• Date of first enrolment: January 18, 2017
• Target sample size: 11
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02960646
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1

Countries of recruitment

United States

Contacts

• Name: Samer Srour
• Affiliation: M.D. Anderson Cancer Center

Key inclusion & exclusion criteria

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



Age minimum: 18 Years
Age maximum: 65 Years
Gender: All

Health Condition(s) or Problem(s) studied

Aplastic Anemia

Therapy-Related Myelodysplastic Syndrome

Acute Myeloid Leukemia

Plasma Cell Myeloma

Myeloproliferative Neoplasm

Recurrent Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

Chronic Myelomonocytic Leukemia

Chronic Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive

Recurrent Hodgkin Lymphoma

Recurrent Non-Hodgkin Lymphoma

Lymphoblastic Lymphoma

Myelodysplastic Syndrome

Acute Lymphoblastic Leukemia

Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome

Recurrent Plasma Cell Myeloma

Blast Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive

Intervention(s)

Drug: Fludarabine Phosphate

Procedure: Peripheral Blood Stem Cell Transplantation

Biological: Filgrastim

Radiation: Total-Body Irradiation

Biological: Rituximab

Drug: Cyclophosphamide

Drug: Melphalan

Drug: Tacrolimus

Other: Laboratory Biomarker Analysis

Primary Outcome(s)

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]

Secondary Outcome(s)

Overall survival (OS) time [Time Frame: Up to 3 years]

Immune reconstitution [Time Frame: Up to 3 years]

Disease free survival (DFS) time [Time Frame: Up to 3 years]

Incidence of infectious episodes [Time Frame: Up to 3 years]

Secondary ID(s)

NCI-2016-01915

2014-0738

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

National Cancer Institute (NCI)