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

• ClinicalTrials.gov Identifier: NCT03272633
• Recruitment Status: Active, not recruiting
• First Posted: September 5, 2017
• Last Update Posted: December 23, 2022
• Sponsor: Rutgers, The State University of New Jersey
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): Roger Strair, MD, PhD, Rutgers Cancer Institute of New Jersey

Tracking Information

• First Submitted Date: August 24, 2017
• First Posted Date: September 5, 2017
• Last Update Posted Date: December 23, 2022
• Actual Study Start Date: October 26, 2020
• Actual Primary Completion Date: June 30, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 1, 2017)

• Disease response in patients who receive irradiated haploidentical cells (IHC) [ Time Frame: Up to 8 weeks after last protocol treatment ]
  It will be determined if there is evidence of disease response to IHC. Disease response will use standard disease-specific parameters.
• Incidence of toxicities associated with administration of irradiated haploidentical cells (IHC) evaluated according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: Up to 12 weeks of completion of therapy ]
  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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: September 1, 2017)

Induction of host T cells reactive with tumor associated epitopes [ Time Frame: Up to 8 weeks after last protocol treatment ]

It will be determined if treatment with the irradiated cells induces an immune response targeting tumor associated epitopes.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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
• 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.

• Study Type: Interventional
• Study Phase: Early Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• 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

Intervention

• Procedure: Allogeneic Hematopoietic Stem Cell Transplantation
  Receive IHC
  Other Names:

  • Allogeneic Hematopoietic Cell Transplantation
  • allogeneic stem cell transplantation
  • HSC
  • HSCT
• Biological: Irradiated Allogeneic Cells
  Correlative studies

Study Arms

• Experimental: Cohort I (initial IHC within 42 days)
  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.
  Interventions:

  • Procedure: Allogeneic Hematopoietic Stem Cell Transplantation
  • Biological: Irradiated Allogeneic Cells
• Experimental: Cohort II (initial IHC within 70 days or after relapse)
  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.
  Interventions:

  • Procedure: Allogeneic Hematopoietic Stem Cell Transplantation
  • Biological: Irradiated Allogeneic Cells

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: November 29, 2022): 4
• Original Estimated Enrollment (submitted: September 1, 2017): 40
• Estimated Study Completion Date: November 15, 2023
• Actual Primary Completion Date: June 30, 2022 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03272633
• Other Study ID Numbers: Pro20170000537; NCI-2017-01537 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ); Pro20170000537; 011702 ( Other Identifier: Rutgers Cancer Institute of New Jersey ); P30CA072720 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: Yes

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: Not Provided
• Current Responsible Party: Roger Strair, MD, PhD, Rutgers Cancer Institute of New Jersey
• Original Responsible Party: Rutgers, The State University of New Jersey
• Current Study Sponsor: Rutgers, The State University of New Jersey
• Original Study Sponsor: Same as current
• Collaborators: National Cancer Institute (NCI)

Investigators

• Principal Investigator: Roger Strair; Rutgers Cancer Institute of New Jersey

• PRS Account: Rutgers, The State University of New Jersey
• Verification Date: December 2022