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Irradiated Donor Cells Following Stem Cell Transplant in Controlling Cancer in Patients With Hematologic Malignancies

Primary Purpose

Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia in Remission, Hematopoietic Cell Transplantation Recipient

Status
Terminated
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
Allogeneic Hematopoietic Stem Cell Transplantation
Irradiated Allogeneic Cells
Sponsored by
Rutgers, The State University of New Jersey
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Lymphoblastic Leukemia

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Patient with disease (stage) eligible per cohort

  • COHORT 1: patients undergoing high dose chemotherapy with autologous stem cell rescue and ?high-risk? disease as defined below:

    • Diffuse large cell lymphoma or peripheral T cell lymphoma (including specified World Health Organization [WHO] subtypes) not in computed tomography (CT)-positron emission tomography (PET) complete remission at time of high dose therapy
    • Diffuse large cell lymphoma with ?double hit? or ?double expressor? features
    • Diffuse large cell lymphoma or peripheral T cell lymphoma (including WHO specified subtypes) refractory to standard induction therapy OR relapsing within 1 year of treatment OR in greater that second complete remission (CR)
    • Mantle cell lymphoma not in CR1

    • Multiple myeloma with ONE (or more) of the following high risk features:

      • Less than very good partial remission at time of high dose therapy
      • High Revised-International Staging System (R-ISS) (stage III ? 2 microglobulin >= 5.5 plus lactate dehydrogenase [LDH] > upper limit of normal [ULN] and/or del17p, t(4;14), t(14;16)) at time of diagnosis
      • Cytogenetics or fluorescent in situ hybridization (FISH) del17p

  • COHORT 2: patients with high risk disease having undergone an allogeneic hematopoietic stem cell transplant from a 10/10 human leukocyte antigen (HLA) matched donor with one of the following disease subtypes:

    • Acute myeloid leukemia (AML) in CR1 with high risk features (European Leukemia Network [ELN]) at presentation

      • Diagnostic sample with either t(6;9), t(9;22), 11q23, inv 3, -5, -7, del17p, complex cytogenetics, NPMwt-flt3ITD+, OR p53 mutation (mut); patients whose samples have mutations in RUNX1 or ASXL1 are also eligible (unless the patient has favorable cytogenetics)
    • AML in CR1 with measurable minimal residual disease (MRD) by molecular (e.g., myeloid mutation profile, polymerase chain reaction [PCR] for NPM1, core-binding factor [CBF], mixed lineage leukemia [MLL]) or flow cytometry
    • AML not in CR1 (including patients with morphologic CR but with incomplete recovery, CRi)
    • Myelodysplastic syndrome (MDS) with complex cytogenetics, 17p deletion or p53 mutation, or JAK2 or RAS mutation
    • Treatment-related MDS or AML
    • Acute lymphoblastic leukemia (ALL) not in CR1
    • ALL with MRD
    • Any hematologic malignancy relapsed or with persistent disease after allogeneic hematopoietic stem cell transplant
    • Multiple myeloma
    • Non-Hodgkin lymphoma (NHL) with chemoresistant disease at time of transplant
    • Any patient undergoing allogeneic hematopoietic stem cell transplant and an anticipated rate of relapse > 80% based upon published data and for which there is consensus amongst the Hematologic Malignancies Tumor Study Group that enrollment is appropriate
  • Availability of a genetic child, genetic parent or sibling as a potential HLA haploidentical donor
  • Meets standard eligibility requirements for high dose chemotherapy with autologous stem cell rescue (COHORT 1) or allogeneic hematopoietic stem cell transplant (COHORT 2) and has signed consent for those procedures
  • DONOR: Donor must be related to patient and be partially (>= 3/6 antigen) HLA-matched

  • DONOR: Donor must meet all Robert Wood Johnson (RWJ) Blood Services requirements for hematopoietic stem cell donation including:

    • Age >= 18 years old;
    • Normal hemogram (white blood cells [WBC] 4.0-10.0 x 10^3/mm^3; platelet count 150,000 to 440,000/mm^3 ; hemoglobin/hematocrit; 12.5-18 g/dl, 38 to 54%
    • Not pregnant or lactating;
    • Not human immunodeficiency virus (HIV)-1, HIV-2, hepatitis C virus (HCV), hepatitis B core or human T-cell lymphotropic virus (HTLV)-I/II seropositive; hepatitis B surface antigen (HB S ag) (-); meet other infectious disease screening criteria utilized by RWJ Blood Services;
    • No uncontrolled infections, other medical or psychological/social conditions, or medications that might increase the likelihood of patient or donor adverse effects or poor outcomes;
    • Meet other blood bank criteria for blood product donation (as determined by RWJ Blood Center screening history and laboratory studies)

Exclusion Criteria:

  • Non-English speaking person
  • Patients undergoing haploidentical allogeneic hematopoietic stem cell transplants are not eligible; patients undergoing < 10/10 HLA allele matched allogeneic transplant are not eligible
  • Pregnant women
  • DONOR: Non-English speaking person
  • DONOR: Pregnant women

Sites / Locations

  • Rutgers Cancer Institute of New Jersey

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Cohort I (initial IHC within 42 days)

Cohort II (initial IHC within 70 days or after relapse)

Arm Description

Within 42 days after hematopoietic engraftment (both neutrophils and platelets) after autologous HSCT, patients receive initial treatment with IHC. Patients that do not have evidence of relapse or progressive disease may be treated every 8-12 weeks for up to 3 doses.

Patients with high-risk disease receive initial treatment with IHC within 70 days after hematopoietic engraftment (both neutrophils and platelets) after allogeneic HSCT. Patients being treated for relapsed disease may receive initial treatment with IHC any time after relapse is documented. Patients that do not have evidence of relapse or progressive disease may be treated every 8-12 weeks for up to 3 doses.

Outcomes

Primary Outcome Measures

Number of Participants Who Received Irradiated Haploidentical Cells (IHC) With Disease Response
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR
the Number of Participants With Toxicities Associated With Administration of Irradiated Haploidentical Cells (IHC) Evaluated According to Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0
The anticipated/projected IHC-associated toxicities of greatest concern include: short-term toxicities- constitutional/systemic adverse events including fevers, hypotension, pulmonary infiltrates; long-term toxicities: autoimmune effects, graft-versus-host disease (GVHD), graft rejection. Toxicity will be measured by occurrence of any experimental treatment-related adverse events (AE) up to 12 weeks of completion of therapy. The CTCAE version 4.0 will be utilized for the description and grading of the AE. All symptoms, signs, or diseases assessed as experimental treatment-related will be captu

Secondary Outcome Measures

Induction of Host T Cells Reactive With Tumor Associated Epitopes
It will be determined if treatment with the irradiated cells induces an immune response targeting tumor associated epitopes.

Full Information

First Posted
August 24, 2017
Last Updated
June 23, 2023
Sponsor
Rutgers, The State University of New Jersey
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT03272633
Brief Title
Irradiated Donor Cells Following Stem Cell Transplant in Controlling Cancer in Patients With Hematologic Malignancies
Official Title
Post-Transplant Use of Irradiated Haplo-Allogeneic Cells
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Terminated
Why Stopped
Lack of enrollment
Study Start Date
October 26, 2020 (Actual)
Primary Completion Date
June 30, 2022 (Actual)
Study Completion Date
September 22, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Rutgers, The State University of New Jersey
Collaborators
National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This pilot clinical trial studies the side effects of irradiated donor cells following stem cell transplant in controlling cancer in patients with hematologic malignancies. Transfusion of irradiated donor cells (immune cells) from relatives may cause the patient's cancer to decrease in size and may help control cancer in patients receiving a stem cell transplant.
Detailed Description
PRIMARY OBJECTIVES: I. To determine the toxicity associated with the administration of irradiated haploidentical cells (IHC) to patients with high-risk hematologic malignancies. SECONDARY OBJECTIVES: I. To determine if there is evidence of disease response associated with IHC. TERTIARY OBJECTIVES: I. To determine if treatment with the irradiated cells induces an immune response targeting tumor associated epitopes. OUTLINE: Patients are assigned to 1 of 2 cohorts. COHORT I: Within 42 days after hematopoietic engraftment (both neutrophils and platelets) after autologous hematopoietic stem cell transplantation (HSCT), patients receive initial treatment with IHC. Patients that do not have evidence of relapse or progressive disease may be treated every 8-12 weeks for up to 3 doses. COHORT II: Patients with high-risk disease receive initial treatment with IHC within 70 days after hematopoietic engraftment (both neutrophils and platelets) after allogeneic HSCT. Patients being treated for relapsed disease may receive initial treatment with IHC any time after relapse is documented. Patients that do not have evidence of relapse or progressive disease may be treated every 8-12 weeks for up to 3 doses. After completion of study treatment, patients will be followed up within 8 weeks.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia in Remission, Hematopoietic Cell Transplantation Recipient, JAK2 Gene Mutation, Loss of Chromosome 17p, Mantle Cell Lymphoma, Minimal Residual Disease, Myelodysplastic Syndrome, Non-Hodgkin Lymphoma, Plasma Cell Myeloma, RAS Family Gene Mutation, Recurrent Diffuse Large B-Cell Lymphoma, Recurrent Hematologic Malignancy, Recurrent Mature T- and NK-Cell Non-Hodgkin Lymphoma, Refractory Diffuse Large B-Cell Lymphoma, Refractory Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma, Therapy-Related Acute Myeloid Leukemia, Therapy-Related Myelodysplastic Syndrome, TP53 Gene Mutation

7. Study Design

Primary Purpose
Treatment
Study Phase
Early Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
2 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Cohort I (initial IHC within 42 days)
Arm Type
Experimental
Arm Description
Within 42 days after hematopoietic engraftment (both neutrophils and platelets) after autologous HSCT, patients receive initial treatment with IHC. Patients that do not have evidence of relapse or progressive disease may be treated every 8-12 weeks for up to 3 doses.
Arm Title
Cohort II (initial IHC within 70 days or after relapse)
Arm Type
Experimental
Arm Description
Patients with high-risk disease receive initial treatment with IHC within 70 days after hematopoietic engraftment (both neutrophils and platelets) after allogeneic HSCT. Patients being treated for relapsed disease may receive initial treatment with IHC any time after relapse is documented. Patients that do not have evidence of relapse or progressive disease may be treated every 8-12 weeks for up to 3 doses.
Intervention Type
Procedure
Intervention Name(s)
Allogeneic Hematopoietic Stem Cell Transplantation
Other Intervention Name(s)
Allogeneic Hematopoietic Cell Transplantation, allogeneic stem cell transplantation, HSC, HSCT
Intervention Description
Receive IHC
Intervention Type
Biological
Intervention Name(s)
Irradiated Allogeneic Cells
Intervention Description
Correlative studies
Primary Outcome Measure Information:
Title
Number of Participants Who Received Irradiated Haploidentical Cells (IHC) With Disease Response
Description
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR
Time Frame
Up to 8 weeks after last protocol treatment
Title
the Number of Participants With Toxicities Associated With Administration of Irradiated Haploidentical Cells (IHC) Evaluated According to Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0
Description
The anticipated/projected IHC-associated toxicities of greatest concern include: short-term toxicities- constitutional/systemic adverse events including fevers, hypotension, pulmonary infiltrates; long-term toxicities: autoimmune effects, graft-versus-host disease (GVHD), graft rejection. Toxicity will be measured by occurrence of any experimental treatment-related adverse events (AE) up to 12 weeks of completion of therapy. The CTCAE version 4.0 will be utilized for the description and grading of the AE. All symptoms, signs, or diseases assessed as experimental treatment-related will be captu
Time Frame
Up to 12 weeks of completion of therapy
Secondary Outcome Measure Information:
Title
Induction of Host T Cells Reactive With Tumor Associated Epitopes
Description
It will be determined if treatment with the irradiated cells induces an immune response targeting tumor associated epitopes.
Time Frame
Up to 8 weeks after last protocol treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patient with disease (stage) eligible per cohort COHORT 1: patients undergoing high dose chemotherapy with autologous stem cell rescue and ?high-risk? disease as defined below: Diffuse large cell lymphoma or peripheral T cell lymphoma (including specified World Health Organization [WHO] subtypes) not in computed tomography (CT)-positron emission tomography (PET) complete remission at time of high dose therapy Diffuse large cell lymphoma with ?double hit? or ?double expressor? features Diffuse large cell lymphoma or peripheral T cell lymphoma (including WHO specified subtypes) refractory to standard induction therapy OR relapsing within 1 year of treatment OR in greater that second complete remission (CR) Mantle cell lymphoma not in CR1 Multiple myeloma with ONE (or more) of the following high risk features: Less than very good partial remission at time of high dose therapy High Revised-International Staging System (R-ISS) (stage III ? 2 microglobulin >= 5.5 plus lactate dehydrogenase [LDH] > upper limit of normal [ULN] and/or del17p, t(4;14), t(14;16)) at time of diagnosis Cytogenetics or fluorescent in situ hybridization (FISH) del17p COHORT 2: patients with high risk disease having undergone an allogeneic hematopoietic stem cell transplant from a 10/10 human leukocyte antigen (HLA) matched donor with one of the following disease subtypes: Acute myeloid leukemia (AML) in CR1 with high risk features (European Leukemia Network [ELN]) at presentation Diagnostic sample with either t(6;9), t(9;22), 11q23, inv 3, -5, -7, del17p, complex cytogenetics, NPMwt-flt3ITD+, OR p53 mutation (mut); patients whose samples have mutations in RUNX1 or ASXL1 are also eligible (unless the patient has favorable cytogenetics) AML in CR1 with measurable minimal residual disease (MRD) by molecular (e.g., myeloid mutation profile, polymerase chain reaction [PCR] for NPM1, core-binding factor [CBF], mixed lineage leukemia [MLL]) or flow cytometry AML not in CR1 (including patients with morphologic CR but with incomplete recovery, CRi) Myelodysplastic syndrome (MDS) with complex cytogenetics, 17p deletion or p53 mutation, or JAK2 or RAS mutation Treatment-related MDS or AML Acute lymphoblastic leukemia (ALL) not in CR1 ALL with MRD Any hematologic malignancy relapsed or with persistent disease after allogeneic hematopoietic stem cell transplant Multiple myeloma Non-Hodgkin lymphoma (NHL) with chemoresistant disease at time of transplant Any patient undergoing allogeneic hematopoietic stem cell transplant and an anticipated rate of relapse > 80% based upon published data and for which there is consensus amongst the Hematologic Malignancies Tumor Study Group that enrollment is appropriate Availability of a genetic child, genetic parent or sibling as a potential HLA haploidentical donor Meets standard eligibility requirements for high dose chemotherapy with autologous stem cell rescue (COHORT 1) or allogeneic hematopoietic stem cell transplant (COHORT 2) and has signed consent for those procedures DONOR: Donor must be related to patient and be partially (>= 3/6 antigen) HLA-matched DONOR: Donor must meet all Robert Wood Johnson (RWJ) Blood Services requirements for hematopoietic stem cell donation including: Age >= 18 years old; Normal hemogram (white blood cells [WBC] 4.0-10.0 x 10^3/mm^3; platelet count 150,000 to 440,000/mm^3 ; hemoglobin/hematocrit; 12.5-18 g/dl, 38 to 54% Not pregnant or lactating; Not human immunodeficiency virus (HIV)-1, HIV-2, hepatitis C virus (HCV), hepatitis B core or human T-cell lymphotropic virus (HTLV)-I/II seropositive; hepatitis B surface antigen (HB S ag) (-); meet other infectious disease screening criteria utilized by RWJ Blood Services; No uncontrolled infections, other medical or psychological/social conditions, or medications that might increase the likelihood of patient or donor adverse effects or poor outcomes; Meet other blood bank criteria for blood product donation (as determined by RWJ Blood Center screening history and laboratory studies) Exclusion Criteria: Non-English speaking person Patients undergoing haploidentical allogeneic hematopoietic stem cell transplants are not eligible; patients undergoing < 10/10 HLA allele matched allogeneic transplant are not eligible Pregnant women DONOR: Non-English speaking person DONOR: Pregnant women
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Roger Strair
Organizational Affiliation
Rutgers Cancer Institute of New Jersey
Official's Role
Principal Investigator
Facility Information:
Facility Name
Rutgers Cancer Institute of New Jersey
City
New Brunswick
State/Province
New Jersey
ZIP/Postal Code
08903
Country
United States

12. IPD Sharing Statement

Learn more about this trial

Irradiated Donor Cells Following Stem Cell Transplant in Controlling Cancer in Patients With Hematologic Malignancies

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