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T-allo10 Cell Infusion before Donor Stem Cell Transplant in Treating Patients with Relapsed or Refractory Blood Cancer

Trial Status: Active

This phase I trial studies side effects and best dose of T-allo10 cells and to see how well they work when given before donor stem cell transplant in treating patients with blood cancer that has come back or does not respond to treatment. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells (called graft versus host disease). Giving T-allo10 cells before the transplant may help prevent this from happening. 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. The donated stem cells may also replace the patient’s immune cells and help destroy any remaining cancer cells. Giving T-allo10 cells before donor stem cell transplant may work better in treating patients with blood cancer that has come back or dose not respond to treatment.

Inclusion Criteria

  • Acute lymphoblastic leukemia (B- or T-acute lymphoblastic leukemia [ALL]) * Complete response (CR)1-ultra high risk features ** Unfavorable cytogenetics ** Hypodiploidy ** Induction failure ** Minimal residual disease (MRD) positive after consolidation * CR2 ** Any of the high risk features listed in CR1 ** B-ALL: any relapse considered eligible for transplant ** T-ALL * CR 3-any
  • Acute myeloid leukemia * MRD > 5% at day 22 induction 1 * MRD > 0.1% after induction 2 * FMS-like tyrosine kinase (FLT)/internal tandem duplication (ITD) with allelic ratio > 0.4 and MRD > 0.1% at day 29 induction 1 * Translocation (6:9), (8:6), (16:21), monosomy7, monosomy 5, 5q. * M7 with KMT2A rearrangements, inv(16)(p13.3q24.3) [CBFA2T3-GLIS2] or t(11;12)(p15;p13) [NUP98-KDM5A] * AML in 2nd or subsequent CR * Therapy related or secondary AML * Refractory anemia with excess blasts (RAEB) 2
  • Myelodysplastic syndrome
  • Mixed phenotype acute leukemia MRD > 1% after consolidation
  • Non-Hodgkin’s lymphoma (NHL) or Hodgkin’s lymphoma (HL) beyond first remission
  • Subjects 1 and 2 (in cohort 1) will be >= 12 years’ old
  • Available mismatched related (mMRD) or mismatched unrelated (mMUD) donor, HLA matched 8/10 or 9/10
  • Performance status Lansky (age < 16) or Karnofsky score (age >= 16) >= 80%
  • Able and willing to provide written, signed informed consent (assent as appropriate)
  • Serum creatinine < 1.5 x upper limit of normal (ULN) or 24-hour creatinine clearance > 50 ml/min
  • Serum bilirubin =< 2 x ULN
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 10 x ULN
  • Carbon monoxide diffusing capability (DLCO) > 60% predicted (in children, oxygen [O2] saturation > 92% on room air)
  • Left ventricular ejection fraction > 45% (in children, shortening fraction > 26%)
  • Male and female subjects of childbearing potential must agree to use an effective means of birth control to avoid pregnancy throughout the transplant procedure, while on immunosuppression, and if the subject experiences any chronic GvHD
  • DONOR: Donors must meet all criteria for donation as per 21 Code of Federal Regulations (CFR)1271 Subpart C
  • DONOR: Unrelated donors must be >= 18 as per National Marrow Donor Program (NMDP) guidelines
  • DONOR: Related donors will be selected from the patient’s family members and relatives; preference will be given to related donors over the age of 18 whenever possible; if minor donors are to be enrolled, they will be a minimum of 12 years old
  • DONOR: Related donors must meet all requirements to donate as per Lucile Packard Children's Hospital (LPCH) standard of procedure (SOP) for donors.
  • DONOR: Able and willing to provide written, signed informed consent (assent as appropriate)

Exclusion Criteria

  • Prior bone marrow or peripheral blood stem cell transplantation within the last 6 (six) months
  • HLA-matched related or unrelated donor available
  • Any active, uncontrolled infection at the time of enrollment
  • Pregnant or lactating females
  • Any severe concurrent disease which, in the judgment of the investigator, would place the patient at increased risk during participation in the study
  • Any subject with a history of significant renal, hepatic, pulmonary dysfunction, or cardiac dysfunction or on treatment to support cardiac dysfunction
  • Human immunodeficiency virus (HIV)-positive
  • Non-cooperative behavior or non-compliance of the patient and/or of his/her family
  • Received another investigational agent within 30 days of enrollment
  • Patients with Down’s syndrome
  • DONOR: Donors who do not meet 21 CFR 1271 Subpart C requirements per the Food and Drug Administration (FDA) to donate
  • DONOR: Donors who are unwilling or unable to sign informed consent (assent when appropriate)
  • DONOR: Pregnant females will not be eligible to donate as per NMDP and LPCH guidelines

California

Palo Alto
Lucile Packard Children's Hospital Stanford University
Status: ACTIVE
Contact: Rajni Agarwal-Hashmi
Phone: 650-725-9250
Stanford Cancer Institute Palo Alto
Status: ACTIVE
Contact: Rajni Agarwal-Hashmi
Phone: 650-725-9250

PRIMARY OBJECTIVES:

I. To assess the tolerability and safety of escalating doses of T-allo10 cell infusions that can be feasibly manufactured to meet release specifications in mismatched related or mismatched unrelated unmanipulated hematopoietic stem cell transplantation (HSCT) in patients with hematologic malignancies.

SECONDARY OBJECTIVES:

I. To assess the incidence of grade III and IV acute graft versus host disease (GvHD).

EXPLORATORY OBJECTIVES:

I. To assess the incidence and severity of chronic GvHD.

II. To assess the time to immune reconstitution.

III. To assess disease free survival.

OUTLINE: This is a dose-escalation study of T-allo10 cells.

Patients undergo fractionated total body irradiation (FTBI) on days -8 to -5. Patients receive cyclophosphamide intravenously (IV) on days -4 and -3. Patients receive T-allo10 cells IV within 30 minutes of thawing of cells on day -1 and undergo HSCT on day 0.

After completion of study treatment, patients are followed up on days 21, 28, 35, 42, 49, 56 and monthly until day 365.

Trial Phase Phase I

Trial Type Treatment

Lead Organization
Stanford Cancer Institute Palo Alto

Principal Investigator
Rajni Agarwal-Hashmi

  • Primary ID PEDSBMT297
  • Secondary IDs NCI-2017-00911
  • Clinicaltrials.gov ID NCT03198234