Donor Stem Cell Transplant in Treating Patients With High Risk Acute Myeloid Leukemia

NCT01801046 | Terminated Phase 1 DMC FDA Drug

• 2 other identifiers: 9L-11-8NCI-2013-00447
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial studies the side effects of donor stem cell transplant in treating patients with high risk acute myeloid leukemia. Giving low doses of chemotherapy before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells when they do not exactly match the patient's blood. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect)

Conditions

Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Childhood Acute Erythroleukemia (M6); Childhood Acute Megakaryocytic Leukemia (M7); Childhood Acute Monoblastic Leukemia (M5a); Childhood Acute Monocytic Leukemia (M5b); Childhood Acute Myeloblastic Leukemia With Maturation (M2); Childhood Acute Myeloblastic Leukemia Without Maturation (M1); Childhood Acute Myeloid Leukemia in Remission; Childhood Acute Myelomonocytic Leukemia (M4); Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

Outcome Measures

Primary Outcomes (2)

• Induction mortality

  Up to 8 weeks

• Complete remission rate (complete remission [CR] or incomplete remission [CRi])

  Exact 95% confidence intervals will be constructed.

  Up to 3 years

Secondary Outcomes (6)

• Occurrence of serious infections (grade 4) assessed using National Cancer Institute (NCI) Common Terminology for Adverse Events (CTCAE) v4.0

  Up to 3 years

• Time to recovery of absolute neutrophil counts (ANC)

  From stem cell infusion to the first of 3 consecutive days in which the ANC is more than 0.5 x 10^9/L, assessed up to 3 years

• Time to recovery of platelets

  From stem cell infusion until the first of 3 consecutive days in which the platelet count is more than 30 x 10^9/L, assessed up to 3 years

• Incidence of GvHD

  Up to 3 years

• Estimate of clinical outcome as measured by event free survival (EFS)

  From the start of induction until documentation of failure to achieve a CR or CRi during induction, initiation of a salvage therapy, disease recurrence/progression (after induction), or death due to any cause, assessed up to 2 years

Study Arms (1)

Treatment (chemotherapy, G-PBSC)

EXPERIMENTAL

INDUCTION CHEMOTHERAPY: Patients receive mitoxantrone hydrochloride IV on days 1-3 and cytarabine IV on days 1-7. HMMACT: Patients receive G-PBSC on day 9.

Drug: mitoxantrone hydrochloride; Drug: cytarabine; Procedure: peripheral blood stem cell transplantation; Other: laboratory biomarker analysis

Interventions

mitoxantrone hydrochloride DRUG

Given IV

Also known as: CL 232315, DHAD, DHAQ, Novantrone

Treatment (chemotherapy, G-PBSC)

cytarabine DRUG

Given IV

Also known as: ARA-C, arabinofuranosylcytosine, arabinosylcytosine, Cytosar-U, cytosine arabinoside

Treatment (chemotherapy, G-PBSC)

peripheral blood stem cell transplantation PROCEDURE

Undergo HMMACT with G-PBSC

Also known as: PBPC transplantation, PBSC transplantation, peripheral blood progenitor cell transplantation, transplantation, peripheral blood stem cell

Treatment (chemotherapy, G-PBSC)

laboratory biomarker analysis OTHER

Correlative studies

Treatment (chemotherapy, G-PBSC)

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have a histologically and cytological confirmed acute myeloid leukemia, high risk AML defined as:
• Age \> 60, or
• Presence of complex cytogenetic abnormalities (with \> 3 cytogenetic abnormalities), del (7q, -5, -7), t(9,22), 11q(23) or high risk mutations by FISH eg MLL, FLT-3 +
• Secondary AML, or
• A white blood cell count of \> 50 x10\^9/L
• Patients must be medically ineligible for allogeneic stem cell transplant (alloSCTx) or not have a known fully HLA matched sibling for planned sibling transplant.
• Patients must have measurable or evaluable disease
• Diagnosis of AML according to World Health Organization (WHO) diagnostic criteria (at least 20% blasts in the peripheral blood or bone marrow), with French-American-British Cooperative group (FAB) classification other than M3 (acute promyelocytic leukemia), documented by bone marrow aspiration and biopsy performed within 14 days prior to administration of 1st dose of remission induction chemotherapy; if a bone marrow aspirate and biopsy were obtained within 28 days prior to the first dose of remission induction therapy then these tests may be submitted for review at University of Southern California (USC) and a repeat screening bone marrow does not need to be conducted;
• Cohort A: newly diagnosed AML, no prior cytotoxic chemotherapy
• Cohort B: newly diagnosed AML, failed to achieve Complete remission (CR) with single standard Induction chemo.
• Patient has at least one medically fit family member expected to be HLA mismatched at 1-9/10; more commonly and preferred: 4-6/10 loci (parent, sibling, niece/nephew, etc but adult children preferred)
• Absolute neutrophil count (ANC) \> 1500, unless due to direct bone marrow involvement of disease
• Platelets \> 75,000, unless due to direct bone marrow involvement of disease
• Hemoglobin \> 8.0 gm/dL, transfusion allowed
• Serum creatinine \< 2.0 x the upper limits of institutional normal (ULN)

You may not qualify if:

• Cohort A: Patients who have received prior cytotoxic chemotherapy, such as anthracyclines and cytarabine not permitted; but prior treatment with demethylating agents (azacytidine or decitabine, lenalidomide, etc) ALLOWED.
• Cohort B: Patients who have received prior fludarabine, clorarabine or drugs known to target T cells not permitted; but prior standard induction with anthracylines and cytarabine ALLOWED including after demethylating agents.
• Have uncontrolled systemic infections, coagulation disorders, or other major medical illnesses of the cardiovascular or respiratory systems
• Pregnant and/or lactating
• Patients who have had non-biopsy surgery in the last 10 days
• Active central nervous system (CNS) disease; patients with previously treated leptomeningeal disease without evidence of remaining leukemia cells by spinal fluid will be eligible
• Known active autoimmune disorder
• Known to be human immunodeficiency virus (HIV)-positive or have active hepatitis B or C
• Patients concurrently taking the following drugs are excluded: mycophenolate, cyclosporine, prednisone \> 20mg/day, or immunosuppressive agents
• DONOR: Personal or family history of severe sickle cell disease or variant (unless donor has tested negative); testing for the presence of hemoglobin S is not required
• DONOR: Positive infectious disease test as dictated by blood collection center's standard operating procedure (SOP)
• DONOR: Current uncontrolled hypertension
• DONOR: Diabetes mellitus
• DONOR: Active peptic ulcer disease
• DONOR: Pregnant or breast-feeding

Sponsors & Collaborators

• University of Southern California: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

USC Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

MeSH Terms

Conditions

Leukemia, Megakaryoblastic, Acute; Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Congenital Abnormalities; Leukemia, Myelomonocytic, Acute; Leukemia, Erythroblastic, Acute

Interventions

Mitoxantrone; Cytarabine; Peripheral Blood Stem Cell Transplantation

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Myeloproliferative Disorders; Bone Marrow Diseases

Intervention Hierarchy (Ancestors)

Anthraquinones; Anthrones; Anthracenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Quinones; Polycyclic Compounds; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Hematopoietic Stem Cell Transplantation; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative

Study Officials

• Ann Mohrbacher

  University of Southern California

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 26, 2013
• First Posted: February 28, 2013
• Study Start: March 6, 2013
• Primary Completion: July 27, 2017
• Study Completion: August 20, 2017
• Last Updated: March 30, 2018

Record last verified: 2018-03

Locations

US (1)