Relapsed Malignant Blood Cancer After Allogeneic Hematopoietic Stem Cell Transplantation
Relapsed Malignant Blood Cancer After Allogeneic Hematopoietic Stem Cell Transplantation
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).
Background:

 -  Cancer relapse is a significant clinical problem following allogeneic hematopoietic stem
 cell transplantation (allotransplant), affecting up to half of all patients. Effective
 treatment options are extremely limited and, for most cancers, rarely curative.

 -  Several Clinical Center (CC) protocols are evaluating treatment for post-allotransplant
 relapse. Relapse often progresses quickly; patients require rapid assessment of protocol
 options in order to expedite initiation of treatment.

 -  Basic information is needed to improve management of relapse after allotransplant
 clinical information regarding risk of relapse and cancer behavior after allotransplant,
 and information on the biology of relapse after allotransplant in order to identify risk
 factors, target prevention strategies, detect early relapse and develop effective
 treatments.

 Objectives:

 Primary Objective:

 To provide a mechanism for systematic, comprehensive evaluation of individuals with relapsed
 hematologic malignancy after allotransplant and, if available, their donors, to streamline
 identification of protocol options, enrollment and initiation of therapy.

 Eligibility:

 1. Individuals who have received allotransplant treatment for hematologic malignancy
 ("Recipient-Subjects"). Analyses (secondary aims) will consider two comparison cohorts:

 1. Relapse Cohort: Cancer progression, relapse or persistently stable (unremitting)
 disease

 2. Remission (Control) Cohort: Cancer response or remission at/after Day 100

 2. Individuals who are being enrolled on Clinical Center protocols to undergo
 allotransplant therapy for hematologic malignancies and are being evaluated at the
 Clinical Center for planned allotransplantation. (Recipient-Subjects)

 3. Related donors of eligible allotransplant recipients ("Donor-Subjects")

 Design:

 1. Recipient-Subjects will have clinical and research evaluations at baseline and three and
 six months post-allotransplant, at six-month intervals through three years
 post-allotransplant, then yearly. Evaluation after relapse treatment response and for
 new protocol options is permitted.

 2. Donor-Subjects will be enrolled at the time of their clinical evaluation and cell
 collection for Recipient-Subject therapy. Return evaluation for additional clinical
 product collection is permitted.

 3. Accrual Ceiling: 500 consented subjects (350 Recipient-Subjects and 150 Donor-Subjects)
 over 5 years, averaging 70 Recipient-Subjects and 30 Donor-Subjects enrolled per year.
-  INCLUSION CRITERIA:

 RECIPIENT SUBJECTS:

 1. Individuals who are candidates for allotransplant therapy for hematologic malignancies
 and are being evaluated at the Clinical Center for planned allotransplantation.

 2. Individuals who have received allotransplant treatment for hematologic malignancy and
 have:

 1. 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).

 2. An ongoing relationship with a primary oncologist who will continue to provide
 continuity of care during and after study participation.

 3. 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.

 3. 18-99 years.

 4. Ability of subject to understand and the willingness to sign a written informed
 consent document.

 DONOR SUBJECTS:

 1. 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.

 2. Age 18-99 years.

 3. Ability of the subject to understand and the willingness to sign a written informed
 consent document.

 4. 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.

 6. 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.

 EXCLUSION CRITERIA:

 RECIPIENT SUBJECTS:

 1. 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.

 2. 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:

 1. 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.