Clinical Trials /

Phase I/II Study of Treg/Tcon Addback to Partially Matched Related Donor Stem Cells With Myeloablative Conditioning and Post-transplant Cyclophosphamide for High Risk Hematologic Malignancies

NCT01818479

Description:

Open label, dose finding trial to assess the efficacy of Treg/Tcon addback to partially matched related donor stem cells. The maximum tolerated dose will be established using 3 subjects per dose level, with an expansion cohort at the maximum tolerated dose.

Related Conditions:
  • Acute Lymphoblastic Leukemia
  • Acute Myeloid Leukemia
  • Chronic Myelomonocytic Leukemia
  • Hodgkin Lymphoma
  • Juvenile Myelomonocytic Leukemia
  • Multiple Myeloma
  • Myelodysplastic Syndromes
  • Myelofibrosis
  • Non-Hodgkin Lymphoma
Recruiting Status:

Terminated

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Phase I/II Study of Treg/Tcon Addback to Partially Matched Related Donor Stem Cells With Myeloablative Conditioning and Post-transplant Cyclophosphamide for High Risk Hematologic Malignancies
  • Official Title: Phase I/II Study of Treg/Tcon Addback to Partially Matched Related Donor Stem Cells With Myeloablative Conditioning and Post-transplant Cyclophosphamide for High Risk Hematologic Malignancies

Clinical Trial IDs

  • ORG STUDY ID: HCI61077
  • NCT ID: NCT01818479

Conditions

  • High Risk Hematologic Malignancies

Interventions

DrugSynonymsArms
stem cell transplantAll participants

Purpose

Open label, dose finding trial to assess the efficacy of Treg/Tcon addback to partially matched related donor stem cells. The maximum tolerated dose will be established using 3 subjects per dose level, with an expansion cohort at the maximum tolerated dose.

Trial Arms

NameTypeDescriptionInterventions
All participantsExperimental
  • stem cell transplant

Eligibility Criteria

        Inclusion Criteria:

        1. Age 0-70 years 2. Karnofsky or Lansky Performance status >70% 3. High risk hematologic
        malignancy 4. Acute myeloid leukemia (AML) with one or more of the following criteria:
        4a.Poor risk cytogenetics, including -5, 5q-, -7, 7q-, t(9;22); complex cytogenetics (>3
        abnormalities); or normal cytogenetics with Flt3 ITD, in first or subsequent complete
        remission (CR).

        4b. Relapsed or primary refractory AML with <10% blasts in the peripheral blood.

        4c. Subjects in CR1 who required two cycles of induction to achieve remission may be
        included at the discretion of the treating physician.

        4d. Standard risk or intermediate risk cytogenetics in second or subsequent CR (enrolled at
        the discretion of the treating physician).

        5. Acute lymphoblastic leukemia (ALL) with one of the following criteria: 5a. Second or
        subsequent CR 5b. Any PR (no circulating blasts) 5c. High-risk ALL in first CR including
        (Ph+, t(4:11), complex karyotype, hypodiploidy (<44 chromosomes), or positive MRD after
        induction 6. Myelodysplasia, intermediate -2 (score 1.5-2.0) or high risk (score >2.5) by
        the International Prognostic Score System.

        7. Myeloproliferative Disorders (include CMML, AMM or Idiopathic Myelofibrosis, and JMML)
        with excess blasts (>5%) 8. Chronic myeloid leukemia (CML) with one of the following
        criteria: 8a. Second or subsequent chronic phase 8b. Accelerated phase 8c. blast crisis 9.
        Non-Hodgkin's lymphoma (NHL) meeting one of the following criteria: 9a. Relapse after
        autologous stem cell transplantation with evidence of responsive disease.

        9b. Subject with chemosensitive relapse who have no option for autologous stem cell
        transplantation due to blood or marrow involvement or failure to mobilize autologous stem
        cells or are not considered eligible for autologous transplant by their treating physician.

        9c. Hodgkin's Lymphoma: relapse after autologous HCT, chemo-refractory disease 9d. Multiple
        myeloma: per NCCN guidelines. Updated annually at: www.nccn.org 10. No suitable
        HLA-identical sibling donor. 11. No identified 8/8 (based upon A, B, C, DRB1 loci) allele
        matched unrelated donor, or unable to wait sufficient time to procure a 8/8 allele matched
        unrelated donor 12. Available HLA 3-5/6 matched genotypically haploidentical partially
        matched related donor 13. Female subjects must be surgically sterile, postmenopausal
        (minimum 1 year without menses), or agree to use approved form of contraception from the
        time of signing the informed consent form through Day +100. Male subjects must also agree
        to use an approved form of birth control for either themselves or their partner, as
        appropriate, from the time of signing the informed consent form through Day +100.

        14. Able to provide informed consent and have signed an approved consent form that conforms
        to federal and institutional guidelines.

        Exclusion Criteria:

          1. Available HLA identical matched sibling donor (unless having failed a prior allogeneic
             transplant from an HLA identical matched sibling)

          2. Recipient HLA antibodies against donor HLA

          3. Any of the following organ dysfunctions:

               1. Cardiac- left ventricular ejection fraction <40%, symptomatic coronary artery
                  disease, or uncontrolled arrhythmias

               2. Pulmonary- FEV1 or DLco<40% or need for use of supplemental oxygen

               3. Renal- calculated or measured GFR <30 ml/min, dialysis requirement, or prior
                  renal transplant

               4. Hepatic- bilirubin > 2.0, ALT> 2.5 X ULN, cirrhosis

          4. Subjects with active or uncontrolled bacterial, viral, or fungal infections requiring
             systemic therapy.

          5. Subjects who have tested positive for HIV.

          6. Pregnant women, nursing mothers or women of child-bearing potential who are unwilling
             to use medically accepted methods of contraception.
      
Maximum Eligible Age:70 Years
Minimum Eligible Age:N/A
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Rate of acute GVHD
Time Frame:36 months
Safety Issue:
Description:Rate of acute GVHD grade III-IV at Day +100 post transplant

Secondary Outcome Measures

Measure:Rate of Engraftment
Time Frame:36 months
Safety Issue:
Description:Day +28 and +100 neutrophil engraftment
Measure:Survival at Day 100
Time Frame:36 months
Safety Issue:
Description:Day +100 and one year survival Day +100 and one year transplant related mortality Day +100 and one year relapse rates

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Utah

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