Microtransplantation to Treat Refractory or Relapsed Hematologic Malignancies in Younger Patients

NCT02433483 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: MITRELNCI-2015-00691
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

Allogeneic transplant can sometimes be an effective treatment for leukemia. In a traditional allogeneic transplant, patients receive very high doses of chemotherapy and/or radiation therapy, followed by an infusion of their donor's bone marrow or blood stem cells. The high-dose chemotherapy drugs and radiation are given to remove the leukemia cells in the body. The infusion of the donor's bone marrow or blood stem cells is given to replace the diseased bone marrow destroyed by the chemotherapy and/or radiation therapy. However, there are risks associated with allogeneic transplant. Many people have life-threatening or even fatal complications, like severe infections and a condition called graft-versus-host disease, which is caused when cells from the donor attack the normal tissue of the transplant patient. Recently, several hospitals around the world have been using a different type of allogeneic transplant called a microtransplant. In this type of transplant, the donor is usually a family member who is not an exact match. In a microtransplant, leukemia patients get lower doses of chemotherapy than are used in traditional allogeneic transplants. The chemotherapy is followed by an infusion of their donor's peripheral blood stem cells. The objective of the microtransplant is to suppress the bone marrow by giving just enough chemotherapy to allow the donor cells to temporarily engraft (implant), but only at very low levels. The hope is that the donor cells will cause the body to mount an immunologic attack against the leukemia, generating a response called the "graft-versus-leukemia" effect or "graft-versus-cancer" effect, without causing the potentially serious complication of graft-versus-host disease. With this research study, the investigators hope to find out whether or not microtransplantation will be a safe and effective treatment for children, adolescents and young adults with relapsed or refractory hematologic malignancies

Conditions

Acute Myeloid Leukemia (AML); Myelodysplastic Syndrome (MDS)

Keywords

Adolescent; Children; Microtransplant; Leukemia

Outcome Measures

Primary Outcomes (2)

• Number of Participants by Stratum Who Complete 2 Cycles of Therapy

  If two or more patients die from causes other than leukemia progression or experience ≥ Grade 3 GVHD that is associated with detectable donor chimerism due to this protocol, or demonstrate persistent engraftment defined as \>5% donor chimerism at the time of count recovery (ANC \> 0.3 x 10\^9/L and platelet count \> 30 x 10\^/L), then the cohort will close due to intolerability. Any subject who transfers to transplant prior to completion of two courses without experiencing an unacceptable toxicity is considered inevaluable for purposes of evaluating tolerability. Accrual will be halted for intolerability if there are two or more failures in tolerability among the first six subjects who are evaluable for tolerability.

  At the end of therapy cycle 2 (approximately 2-3 months)

• Proportion of Participants Who Experience Therapeutic Success

  All patients will be counted towards this two-stage design. Therapeutic success for patients at time of enrollment is defined as: * Patients with fewer than 5% blasts, a ≥ 10-fold decrease in level of minimal residual disease after completion of 1 or 2 cycles of therapy. * Patients with greater than 5% in leukemic blasts in the marrow, achieving CR or CRi after completion of 1 or 2 cycles of therapy. In terms of efficacy, patients who die before achieving therapeutic success will be counted as a failure, and all patients who receive ≥ 1 dose of protocol chemotherapy will be counted as a failure or success. Only subjects who withdraw or die prior to receiving the first dose of protocol chemotherapy will be considered inevaluable and replaced. The evaluation of tolerability and this phase II design will be performed concurrently, i.e., the first enrollees will be counted for both tolerability and efficacy.

  At the end of therapy cycle 2 (approximately 2-3 months)

Secondary Outcomes (6)

• 3-year Event Free Survival (EFS)

  3 years after enrollment of the last participant

• 3-year Overall Survival (OS)

  3 years after enrollment of the last participant

• Median Time to Neutrophil Recovery

  From start of therapy to completion of therapy (approximately 1 year)

• Time to Platelet Recovery

  From start of therapy to completion of therapy (approximately 1 year)

• 1-year Cumulative Incidence of Acute Graft Versus Host Disease (GVHD)

  From start of therapy through completion of therapy (approximately 1 year)

Other Outcomes (1)

• Percent Donor Chimerism

  At weeks 1, 2, 3, and 4 after infusion of HPC-A

Study Arms (1)

Myeloid Malignancies

EXPERIMENTAL

Includes participants with AML and MDS. Participants receive chemotherapy based on diagnosis followed by infusion of donor HPC-A. Participants with CNS disease receive weekly age-adjusted intrathecal triples therapy until the cerebrospinal fluid becomes free of leukemia (minimum of 4 doses). Interventions: * Cycle 1: cytarabine, HPC-A donor infusion * Cycle 2: Participants who have at least a partial response to Cycle 1 are eligible to receive Cycle 2: cytarabine, HPC-A infusion

Drug: Cytarabine; Drug: Intrathecal Triples; Biological: HPC-A

Interventions

Cytarabine DRUG

Given by either intrathecal (IT) or intravenous (IV) route.

Also known as: Cytosine arabinoside, Ara-C, Cytosar®

Myeloid Malignancies

Intrathecal Triples DRUG

given IT.

Also known as: ITMHA, Methotrexate/hydrocortisone/cytarabine

Myeloid Malignancies

HPC-A BIOLOGICAL

Given IV.

Also known as: Donor infusion, Hematopoietic Progenitor Cell, Apheresis

Myeloid Malignancies

Eligibility Criteria

• Age: Up to 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Participants must have a diagnosis of AML or myelodysplastic syndrome (MDS), ALL, and must have disease that has relapsed or is refractory to chemotherapy, or that has relapsed after HSCT.
• Refractory disease is defined as persistent disease after at least two courses of induction chemotherapy.
• Patients with AML must have ≥ 5% leukemic blasts in the bone marrow or have converted from negative minimal residual disease (MRD) status to positive MRD status in the bone marrow as assessed by flow cytometry. If an adequate bone marrow sample cannot be obtained, patients may be enrolled if there is unequivocal evidence of leukemia in the peripheral blood.
• Participant is ≤ 21 years of age (i.e., has not reached 22nd birthday).
• Adequate organ function defined as the following:
• Total bilirubin ≤ upper limit of normal (ULN) for age, or if total bilirubin is \> ULN, direct bilirubin is ≤ 1.5 mg/dL
• AST (SGOT)/ALT (SGPT) \< 5 x ULN
• Calculated creatinine clearance \> 50 ml/min/1.73m\^2 as calculated by the Schwartz formula for estimated glomerular filtration rate \>
• Left ventricular ejection fraction ≥ 40% or shortening fraction ≥ 25%.
• Has an available HPC-A donor.
• Performance status: Lansky ≥ 50 for patients who are ≤ 16 years old and Karnofsky ≥ 50% for patients who are \> 16 years old.
• Does not have an uncontrolled infection requiring parenteral antibiotics, antivirals, or antifungals within one week prior to first dose. Infections controlled on concurrent anti-microbial agents are acceptable, and anti-microbial prophylaxis per institutional guidelines is acceptable.
• Patient has fully recovered from the acute effects of all prior therapy and must meet the following criteria.
• At least 14 days must have elapsed since the completion of myelosuppressive therapy.
• At least 24 hours must have elapsed since the completion of hydroxyurea, low-dose cytarabine (up to 200 mg/m\^2/day), and intrathecal chemotherapy.

Sponsors & Collaborators

• St. Jude Children's Research Hospital: lead
• Cookies for Kids' Cancer: collaborator

Study Sites (1)

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

Related Links

• St. Jude Children's Research Hospital
• Clinical Trials Open at St. Jude

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Leukemia

Interventions

Cytarabine; Methotrexate; Fecal Microbiota Transplantation; Blood Component Removal

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases

Intervention Hierarchy (Ancestors)

Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Biological Therapy; Therapeutics

Limitations and Caveats

This study was terminated in May 2017 due to poor accrual and because of competing protocols.

Results Point of Contact

• Title: Jeffrey E. Rubnitz, MD, PhD
• Organization: St. Jude Children's Research Hospital

jeffrey.rubnitz@stjude.org

901-595-2388

Study Officials

• Jeffrey E. Rubnitz, MD, PhD

  St. Jude Children's Research Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 29, 2015
• First Posted: May 5, 2015
• Study Start: May 22, 2015
• Primary Completion: May 8, 2017
• Study Completion: May 8, 2017
• Last Updated: November 1, 2017
• Results First Posted: November 1, 2017

Record last verified: 2017-09

Locations

US (1)