Laboratory-Treated Lymphocyte Infusion After Haploidentical Donor Stem Cell Transplant

NCT00376480 | Completed Phase 1 DMC

• 4 other identifiers: 05-030P01CA100265P30CA006516MDA-2005-0695
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 6

Brief Summary

RATIONALE: Giving total-body irradiation and chemotherapy, such as thiotepa and fludarabine, before a donor stem cell transplant helps stop the growth of cancer or abnormal cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving methylprednisolone and antithymocyte globulin before transplant and peripheral blood cells that have been treated in the laboratory after transplant may stop this from happening. PURPOSE: This phase I trial is studying the side effects and best dose of laboratory-treated peripheral blood cell infusion after donor stem cell transplant in treating patients with hematologic cancers or other diseases.

Conditions

Leukemia; Myelodysplastic Syndromes

Keywords

refractory anemia with excess blasts in transformation; adult acute lymphoblastic leukemia in remission; refractory anemia with excess blasts; refractory anemia; adult acute myeloid leukemia in remission; childhood acute lymphoblastic leukemia in remission; childhood acute myeloid leukemia in remission; de novo myelodysplastic syndromes; previously treated myelodysplastic syndromes; secondary acute myeloid leukemia; adult acute myeloid leukemia with 11q23 (MLL) abnormalities; adult acute myeloid leukemia with inv(16)(p13;q22); adult acute myeloid leukemia with t(15;17)(q22;q12); adult acute myeloid leukemia with t(16;16)(p13;q22); adult acute myeloid leukemia with t(8;21)(q22;q22); secondary myelodysplastic syndromes; childhood myelodysplastic syndromes

Outcome Measures

Primary Outcomes (3)

• Feasibility of making and administering the adoptive T cell product

  ability to collect sufficient cells, make anergized product with good viability, without contamination and infuse per study toxicity of the conditioning regimen, the likelihood of engraftment, and the subsequent percentage of individuals who would be eligible to receive aDLI were determined.

  from conditioning through administration of anergized cells on day 35-42

• Safety of administering the adoptive T cell product on day 35-42 post haploidentical transplant

  rates of graft failure with CD34 selected product, adverse and severe adverse reactions attributable to infusion of anergized donor cells, including fever, hypotension, acute graft vs host disease, organ dysfunction

  the period from aDLI infusion through D100

• Alloreactivity engendered by administering the adoptive T cell product

  occurrence and severity of acute GVHD

  from cell infusion through day 100

Secondary Outcomes (1)

• Efficacy in restoring adaptive immunity

  from aDLI thorough 1 year

Study Arms (1)

administration of adoptive donor lymphocyte infusion

EXPERIMENTAL

administration of donor lymphocytes made using costimulatory blockade ex vivo

Biological: anti-thymocyte globulin; Biological: peripheral blood lymphocyte therapy; Drug: fludarabine phosphate; Drug: methylprednisolone; Drug: thiotepa; Procedure: allogeneic hematopoietic stem cell transplantation; Procedure: in vitro-treated peripheral blood stem cell transplantation; Radiation: total-body irradiation

Interventions

anti-thymocyte globulin BIOLOGICAL

administration of adoptive donor lymphocyte infusion

peripheral blood lymphocyte therapy BIOLOGICAL

administration of adoptive donor lymphocyte infusion

fludarabine phosphate DRUG

administration of adoptive donor lymphocyte infusion

methylprednisolone DRUG

administration of adoptive donor lymphocyte infusion

thiotepa DRUG

administration of adoptive donor lymphocyte infusion

allogeneic hematopoietic stem cell transplantation PROCEDURE

administration of adoptive donor lymphocyte infusion

in vitro-treated peripheral blood stem cell transplantation PROCEDURE

administration of adoptive donor lymphocyte infusion

total-body irradiation RADIATION

administration of adoptive donor lymphocyte infusion

Eligibility Criteria

• Age: Up to 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

DISEASE CHARACTERISTICS: * Diagnosis of 1 of the following: * Acute lymphocytic leukemia * In ≥ second complete remission (CR), defined as \< 5% blasts in bone marrow (BM) and no active extramedullary disease OR in first CR with any of the following high risk features: * History of induction failure * Philadelphia chromosome positive * t(4;11) by cytogenetic analysis * Any infant with MLL rearrangements on cytogenetic analysis * No relapse with isolated extramedullary disease after completion of prior treatment * Acute myeloid leukemia * Failed induction therapy after \< 3 courses * In ≥ second CR, defined as \< 5% blasts in BM and no active extramedullary disease OR in first CR with any of the following high-risk features: * History of induction failure = 5q- or monosomy 7 cytogenetic findings * Any of the following myelodysplastic syndromes: * Refractory anemia (RA) with excess blasts (RAEB) with a high International Prognostic Scoring System (IPSS) score or score of intermediate-1(INT-1) or intermediate-2 (INT-2) * RAEB in transformation with INT-1, INT-2, or high IPSS score * RA with INT-2 score * Patients must have a healthy, related donor who is at least genotypically HLA-A, B, C, and DR haploidentical to the patient * No suitably matched family donor defined by genotypic or phenotypic identity for ≥ 5/6 A, B, or DR loci * No immediately available genotypically matched (6/6) unrelated marrow donor * No immediately available umbilical cord blood donor with suitable cell dose after a search ≥ 2 months * Patients whose medical condition is at high risk of deteriorating or whose disease is at high risk of progression during a donor search are eligible * Has a parent with a haplotype that is disparate from that of the donor for the haplotype shared by the patient and parent, but not shared by the patient and donor OR patient is able to donate sufficient autologous cells by peripheral blood draw or unstimulated leukapheresis * No active CNS disease PATIENT CHARACTERISTICS: * Room air O\_2 saturation \> 95% unless the lungs are involved with disease * No clinical evidence of pulmonary insufficiency unless the lungs are involved with disease * AST and ALT \< 3 times upper limit of normal (ULN)\* * Bilirubin \< 2.0 mg/dL\* * Creatinine \< 2 times ULN OR creatinine clearance or glomerular filtration rate \> 50% of the lower limit of normal * LVEF \> 45% OR shortening fraction \> 20% * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * No active infection, defined as absence of an infectious diagnosis or (in patients who have had a recent positive infectious diagnosis) the resolution of fever, documentation of negative cultures or antigen testing, continuation or completion of a course of appropriate therapy, and presence of stable to resolving clinical symptoms * No evidence of HIV infection OR known HIV positivity NOTE: \*Does not apply if liver is involved with disease PRIOR CONCURRENT THERAPY: * See Disease Characteristics * No prior stem cell transplantation * No other concurrent immunosuppressive therapy

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• National Cancer Institute (NCI): collaborator
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (6)

Childrens Hospital Los Angeles

Los Angeles, California, 90027-0700, United States

Location

University of Florida Health Science Center - Gainesville

Gainesville, Florida, 32610, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Children's Hospital Boston

Boston, Massachusetts, 02115, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

M. D. Anderson Cancer Center at University of Texas

Houston, Texas, 77030-4009, United States

Location

Related Publications (1)

• Davies JK, Brennan LL, Wingard JR, Cogle CR, Kapoor N, Shah AJ, Dey BR, Spitzer TR, de Lima M, Cooper LJ, Thall PF, Champlin RE, Nadler LM, Guinan EC. Infusion of Alloanergized Donor Lymphocytes after CD34-selected Haploidentical Myeloablative Hematopoietic Stem Cell Transplantation. Clin Cancer Res. 2018 Sep 1;24(17):4098-4109. doi: 10.1158/1078-0432.CCR-18-0449. Epub 2018 May 16.

  PMID: 29769208 RESULT

MeSH Terms

Conditions

Leukemia; Myelodysplastic Syndromes; Anemia, Refractory, with Excess of Blasts; Anemia, Refractory; Congenital Abnormalities

Interventions

Antilymphocyte Serum; fludarabine phosphate; Methylprednisolone; Thiotepa; Whole-Body Irradiation

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases; Anemia; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures; Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Phosphoramides; Organophosphorus Compounds; Organic Chemicals; Triethylenephosphoramide; Aziridines; Azirines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Radiotherapy; Therapeutics; Investigative Techniques

Study Officials

• Eva Guinan, MD

  Dana-Farber Cancer Institute

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 13, 2006
• First Posted: September 15, 2006
• Study Start: June 1, 2005
• Primary Completion: June 1, 2010
• Study Completion: May 16, 2018
• Last Updated: July 5, 2019

Record last verified: 2019-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (6)