Relapsed Malignant Blood Cancer After Allogeneic Hematopoietic Stem Cell Transplantation

NCT01326728 | Terminated Results

• 2 other identifiers: 11012511-C-0125
• Study Type: observational
• Target: 56
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Allogeneic hematopoietic stem cell transplantation (or allotransplant; donor blood stem cells) have been used with varying degrees of success as an immune therapy for blood-system cancers (leukemias, myelodysplastic syndrome, lymphomas, multiple myeloma, etc.). Some people s cancer remains active (comes back or continues to spread) after an allotransplant, while other peoples cancer disappears and they are hopefully cured. National Institutes of Health (NIH) researchers are studying the reasons for these different treatment outcomes, and trying to develop better cancer treatments for people with active cancer after allotransplant. Researchers are collecting data from people who have had allotransplants for a cancer of the blood, whether or not the cancer is in remission, and from their donors. Those with active cancers may be eligible to participate in one of several NIH studies testing treatments for active cancer after allotransplant. Objectives:

• To develop a systematic, comprehensive evaluation of individuals with relapsed malignant blood cancers after allotransplant (and, if available, their donors) to identify potential treatment study options
• To compare the immune system after allotransplant between people whose cancers are growing with people whose cancers remain in remission.
• To compare the immune system after cancer relapse/progression treatment between people whose cancer responds to treatment with those whose cancers continue to grow. Eligibility:
• Individuals whose blood system cancer grows or comes back after receiving allotransplant treatment.
• Individuals whose blood system cancer is responding or in remission 100 days or more after receiving allotransplant treatment.
• Related stem-cell donors of eligible allotransplant recipients. Design:
• Participants will be evaluated with a full physical examination, detailed medical history (for recipients, including a history of allotransplant treatment process, side-effects, etc.), and blood tests. Recipients will also have imaging studies, possible tissue biopsies, quality of life questionnaires/assessments, and other tests to evaluate the current state of their cancer, whether active or in remission. In some cases, it may be possible to substitute results from recent tests and/or biopsies.
• Healthy related donors will have apheresis to provide white blood cells for study and/or for use in potential treatment options. If stem cells would be medically helpful to a recipient, their donors might be asked to take injections of filgrastim before the apheresis procedure to stimulate the production of stem cells for collection.
• As feasible, all recipients will be asked to return to the NIH for detailed follow-up visits in conjunction with 6, 12, and 24 months post-allotransplant evaluations, and may be monitored between visits.
• Recipients whose cancers are active and who are found to be eligible for treatment protocols at the NIH will continue to be monitored on this study while participating on treatment protocols. Return visits and follow-up tests for this study will be coordinated with those required by the treatment protocol.
• Participants may return in the future to be evaluated for new treatment study options (recipients) or additional cell donations for therapy (donors).

Conditions

Chronic Myelogenous Leukemia; Acute Myelogenous Leukemia; Acute Lymphoblastic Leukemia; Hodgkins Lymphoma; Non-Hodgkins Lymphoma

Keywords

Relapse; Hematologic Malignancy; Allogeneic; Hematopoietic Stem Cell Transplantation; Leukemia; Lymphoma; Hodgkin Lymphoma

Outcome Measures

Primary Outcomes (7)

• Immune Suppression

  Biological response to agents and or treatments that can lead to bone marrow suppression/ cytopenias and sometimes death.

  up to 100 days or more following transplant

• Time to Progression After Allotransplant

  Time to Progression is the time between the first day of treatment to day 100 after allotransplant.

  first day of treatment to day 100 after allotransplant

• Overall Survival

  Overall Survival is the time between the first day of treatment to the day of death.

  first day of treatment to the day of death

• Days to Engraftment

  Number of days for a participant to reach engraftment.

  up to 100 days or more following allotransplant

• Count of Participants With Acute Graft Versus Host Disease (GVHD) Grade 2 or More 100 Days Post Allotransplant

  Acute GVHD is defined as GVHD that presents with signs and symptoms typical of acute GVHD but presenting after day 100 post allotransplant. Clinical Staging Grade 2 ((+) to (+++) Skin; (+) Liver; and (+) Gut) involvement, Grade 3 ((++) to (+++) Skin; (++ to +++) Liver; and (++ to +++) Gut) involvement, and Grade 4 ((++) to (++++) Skin; (++ to ++++) Liver; and (++ to ++++) Gut) involvement.

  100 days or more post allotransplant

• Count of Participants With Chronic Graft Versus Host Disease (GVHD) Grade 2 or More 100 Days Post Allotransplant

  Mild chronic GVHD involves only 1 or 2 organs or sites with no clinically significant functional impairment (max. score of 1 in all affected organs or sites). Moderate GVHD involves at least 1 organ or site with clinically significant but no major disability (max. score of 2 in any affected organ or site), or 3 or more organs or sites with no clinically significant functional impairment (max. score of 1 in all affected organs or sites), and a lung score of 1 will also be considered moderate chronic GVHD. Severe chronic GVHD indicates major disability caused by chronic GVHD (score of 3 in any organ or site). A lung score of 2 or greater will also be considered severe chronic GVHD.

  100 days post allotransplant

• Count of Participants With Infection After Allotransplant

  Count of Participants with Infection After Allotransplant.

  up to 100 days or more post allotransplant

Secondary Outcomes (1)

• Number of Participants With Serious and Non-Serious Adverse Events

  5 years

Other Outcomes (5)

• Count of Participants With Clinical Blood Markers of Inflammation

  up to 100 days or more following allotransplant

• Regimen-Specific Sensitivity After Allotransplant

  up to 100 days or more following allotransplant

• Tumor Immune Response Graft-Versus-Leukemia (GVL)

  up to 100 days or more following allotransplant

Study Arms (1)

Allogeneic Stem Cell Transplant

Allogeneic hematopoietic stem cell transplantation (or allotransplant; donor blood stem cells)

Biological: Allogeneic stem cell transplant

Interventions

Allogeneic stem cell transplant BIOLOGICAL

Donors will undergo cell collection and recipients will receive cells (allotransplant).

Allogeneic Stem Cell Transplant

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Individuals aged 18-99 who are being enrolled on Clinical Center protocols to undergo allotransplant therapy for hematologic malignancies. The population will consist of those that have received allotransplant treatment for hematologic malignancy, are in remission either at or after Day 100, have malignancy progression or persistently stable disease post allotransplant, or the related donor of eligible allotransplant recipients.

You may qualify if:

• RECIPIENT SUBJECTS:
• Individuals who are candidates for allotransplant therapy for hematologic malignancies and are being evaluated at the Clinical Center for planned allotransplantation.
• Individuals who have received allotransplant treatment for hematologic malignancy and have:
• Hematologic recovery after allotransplant: e.g., have had neutrophil recovery to 500 cells/mcL. Secondary cytopenias or cytopenias due to disease progression will be permitted. Note: this requirement will not apply to subjects enrolling pre-transplant, i.e, who receive transplant-related medical care at the Clinical Center (CC).
• An ongoing relationship with a primary oncologist who will continue to provide continuity of care during and after study participation.
• Following record review and information exchange between the patients primary oncologist and the National Cancer Institute (NCI) Principal Investigator (PI)/Designee, the PI/Designee determines that the individual reasonably could be expected to safely tolerate travel to and from the Clinical Center (CC) to undergo evaluation as defined in the protocol, in the event that the patient is ineligible or uninterested in participating in open treatment protocols.
• years.
• Ability of subject to understand and the willingness to sign a written informed consent document.
• DONOR SUBJECTS:
• Individuals who are/will be the donors of allogeneic hematopoietic stem cell transplants received by Recipient-Subjects who are to be enrolled on this protocol.
• Age 18-99 years.
• Ability of the subject to understand and the willingness to sign a written informed consent document.
• Individuals with evidence of infection with transfusion-transmittable agents (Hepatitis B and C Viruses (HBV, HCV); Human Immunodeficiency Virus (HIV (Omega)), Human TLymphotrophic Virus (HTLV I/II), West Nile Virus (WNV) and Trypanosoma cruzi) will not be excluded from study participation. However, Donor-Subjects with evidence of HIV infection will only be able to donate cells for research. Donors with a history of HBV or HCV infection will be able to donate for research, and may be eligible to donate for therapeutic administration. However, determination of permissibility for clinical donation will require a hepatology consultation and the consent of the intended recipient after discussion of the risk/benefit of the donor cell product and the possibility/consequences of transmission. The PI/Designee will make the final determination of permissibility of donation for recipient cell therapy.
• \. Unrelated donor selection will be in accordance with the National Marrow Donor Program (NMDP) standards. When a potentially eligible recipient of an unrelated donor product from an NMDP Center is identified, the recipient will complete an NMDP search transfer request to allow NIH NMDP staff to contact the NMDP Coordinating Center, who will, in turn, contact the donors prior Donor Center. The NMDP Policy for Subsequent Donation Requests will be followed and the appropriate forms (Subsequent Donation Request Form and Therapeutic T Cell Collection Prescription Form) will be submitted as required.

You may not qualify if:

• RECIPIENT SUBJECTS:
• Individuals with rapid disease progression or aggressive cancer histology who, in the opinion of the PI/Designee, require urgent therapy within 30 days in order to preserve organ function or quality of life. This restriction will not apply if there is no approved therapy with a reasonable chance of disease response, if the patient does not have access to an effective therapy and the patient appears to be eligible for an accruing CC treatment protocol or if the patient is enrolled on an NIH/CC clinical protocol, e.g., allotransplant protocol.
• Pregnancy or lactating. Additionally, Recipient-Subjects of childbearing potential that will receive cancer treatment under this protocol must be willing to use an effective method of contraception.
• DONOR SUBJECTS:
• \. Adult donors who are not eligible for clinical donation will not be excluded from study participation, but will only be able to donate cells for research.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Pavletic SZ, Kumar S, Mohty M, de Lima M, Foran JM, Pasquini M, Zhang MJ, Giralt S, Bishop MR, Weisdorf D. NCI First International Workshop on the Biology, Prevention, and Treatment of Relapse after Allogeneic Hematopoietic Stem Cell Transplantation: report from the Committee on the Epidemiology and Natural History of Relapse following Allogeneic Cell Transplantation. Biol Blood Marrow Transplant. 2010 Jul;16(7):871-90. doi: 10.1016/j.bbmt.2010.04.004. Epub 2010 Apr 24.

  PMID: 20399876 BACKGROUND

• Dazzi F, Fozza C. Disease relapse after haematopoietic stem cell transplantation: risk factors and treatment. Best Pract Res Clin Haematol. 2007 Jun;20(2):311-27. doi: 10.1016/j.beha.2006.10.002.

  PMID: 17448964 BACKGROUND

• Porter DL, Alyea EP, Antin JH, DeLima M, Estey E, Falkenburg JH, Hardy N, Kroeger N, Leis J, Levine J, Maloney DG, Peggs K, Rowe JM, Wayne AS, Giralt S, Bishop MR, van Besien K. NCI First International Workshop on the Biology, Prevention, and Treatment of Relapse after Allogeneic Hematopoietic Stem Cell Transplantation: Report from the Committee on Treatment of Relapse after Allogeneic Hematopoietic Stem Cell Transplantation. Biol Blood Marrow Transplant. 2010 Nov;16(11):1467-503. doi: 10.1016/j.bbmt.2010.08.001. Epub 2010 Aug 10.

  PMID: 20699125 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Blood and tissue specimens collected in the course of this research project may be cryopreserved and used in the future to investigate new scientific questions related to the study.

MeSH Terms

Conditions

Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Hodgkin Disease; Lymphoma, Non-Hodgkin; Recurrence; Hematologic Neoplasms; Leukemia; Lymphoma

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Neoplasms by Histologic Type; Neoplasms; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Neoplasms by Site

Results Point of Contact

• Title: Dr. Ronald Gress
• Organization: National Cancer Institute

gressr@mail.nih.gov

301-496-1791

Study Officials

• Ronald E Gress, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 30, 2011
• First Posted: March 31, 2011
• Study Start: March 30, 2011
• Primary Completion: June 28, 2017
• Study Completion: July 14, 2017
• Last Updated: June 6, 2018
• Results First Posted: June 6, 2018

Record last verified: 2018-05

Locations

US (1)