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| ID | Type | Description | Link |
|---|---|---|---|
| RP01-05 |
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RATIONALE: Giving low doses of chemotherapy before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. It also stops the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune system and help destroy any remaining cancer cells (graft-versus-tumor effect). Giving an infusion of the donor's T cells (donor lymphocyte infusion) after the transplant may help increase this effect. Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving immunosuppressive therapy before or after the transplant may stop this from happening.
PURPOSE: This phase II trial is studying how well chemotherapy followed by donor peripheral stem cell transplant works in treating patients with hematologic cancer or aplastic anemia.
OBJECTIVES:
OUTLINE:
Preparative regimen:
Matched related and unrelated donor transplantation:
Cord blood transplantation:
Graft-vs-host disease (GVHD) prophylaxis:
Matched related and unrelated donor transplantation:
Cord blood transplantation:
Allogeneic stem cell reinfusion: Patients undergo allogeneic bone marrow or peripheral blood stem cell transplantation on day 0. Patients then receive sargramostim (GM-CSF) subcutaneously daily beginning on day 7 and continuing until blood counts recover.
Donor lymphocyte infusion (DLI): Patients not converting to 100% donor T-cell chimerism by day 120 and showing signs of progresson of disease after tacrolimus and MMF withdrawal may receive DLI every 8 weeks for up to 3 infusions. Cord blood recipients do not receive DLI.
Patients are followed at day 100-120, every 3 months for 2 years, and then every 6 months for 5 years.
PROJECTED ACCRUAL: A total of 30-60 patients will be accrued for this study within 6-7 years.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| All patients | Experimental | All patients enrolled on study |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| anti-thymocyte globulin | Biological | iv |
| |
| graft-versus-tumor induction therapy |
| Measure | Description | Time Frame |
|---|---|---|
| Day 100 TRM | treatment related mortality within 100 days from hematopoietic stem cell (HSC) infusion on day 0 | from start or conditioning (day -6 or -5) through day +100 after HSC infusion |
| Day 100 Best Response | Best disease response measured within 100 days from hematopoietic stem cell (HSC) infusion on day 0 using disease specific response criteria defined in the protocol | from start of conditioning on day -6 or -5 through day +100 after HSC infusion |
| Measure | Description | Time Frame |
|---|---|---|
| PFS | Progression free survival defined as time from HSC infusion (day 0) until progression of disease or death due to any cause. Patients are censored if alive without disease progression through 1 year after HSC infusion | 1 year |
| OS |
Not provided
DISEASE CHARACTERISTICS:
Diagnosis of aplastic anemia
Histologically confirmed hematologic malignancy including the following:
Acute leukemia
Any of the following types:
Resistant or recurrent disease after combination chemotherapy with at least 1 standard regimen OR
In first remission at high risk of relapse
Chronic myelogenous leukemia
Chronic phase meeting at least 1 of the following criteria:
Accelerated phase (blasts less than 20%)
Myeloproliferative and myelodysplastic syndromes
Lymphoproliferative disease
Chronic lymphocytic leukemia
Low-grade non-Hodgkin's lymphoma (recurrent or persistent)
Multiple myeloma
Waldenstrom's macroglobulinemia
Non-Hodgkin's lymphoma meeting the following criteria:
Hodgkin's lymphoma
Not eligible for standard myeloablative allogeneic stem cell transplantation
Availability of any of the following donor types:
Related donor matched at 5 or 6 HLA antigens (A, B, DR)
Unrelated donor fully matched by molecular analysis at A, B, DRB1, and DQB1 loci
Cord blood that is 4, 5, or 6 match with recipient HLA antigens (A, B, DR) NOTE: No syngeneic donors permitted
No uncontrolled CNS disease (for hematologic malignancies) NOTE: A new classification scheme for adult non-Hodgkin's lymphoma has been adopted by PDQ. The terminology of "indolent" or "aggressive" lymphoma will replace the former terminology of "low", "intermediate", or "high" grade lymphoma. However, this protocol uses the former terminology.
PATIENT CHARACTERISTICS:
Age
Performance status
Life expectancy
Hematopoietic
Hepatic
Renal
Cardiovascular
Pulmonary
Other
PRIOR CONCURRENT THERAPY:
Biologic therapy
Chemotherapy
Endocrine therapy
Radiotherapy
Surgery
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| Name | Affiliation | Role |
|---|---|---|
| Philip L. McCarthy, MD | Roswell Park Cancer Institute | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Roswell Park Cancer Institute | Buffalo | New York | 14263-0001 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | All Patients | All patients enrolled on study Patients received cyclophosphamide 50 mg/kg on days -5 and -4, and fludarabine 25 mg/m2 on days -5, -4, -3, -2, -1. Hematopoietic cells from peripheral blood or marrow were infused on day 0. Patients who received hematopoietic cells from cord blood additionally received ATG 30 mg/kg on days -3, -2, -1. Fanconi anemia patients received cyclophosphamide 7.5 mg/kg on days -6, -5, -4, -3, fludarabine 25 mg/m2 on days -6, -5, -4, -3, -2 and ATG 30 mg/kg on days -3, -2, -1 and hematopoietic cells infused on day 0. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Oct 19, 2018 |
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| Biological |
iv |
|
| sargramostim | Biological | iv |
|
| therapeutic allogeneic lymphocytes | Biological | iv |
|
| cyclophosphamide | Drug | injection |
|
| fludarabine phosphate | Drug | iv |
|
|
| methylprednisolone | Drug | oral |
|
| mycophenolate mofetil | Drug | oral |
|
| tacrolimus | Drug | oral |
|
| allogeneic bone marrow transplantation | Procedure | iv |
|
| peripheral blood stem cell transplantation | Procedure | iv |
|
| umbilical cord blood transplantation | Procedure | iv |
|
Overall survival with events defined as death due to any cause and censored patients are alive as of 1 year post HSC infusion
| 1 year |
| Acute GvHD | overall grade II-IV acute GvHD | Day +100 |
| COMPLETED |
|
| NOT COMPLETED |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | All Patients | All patients enrolled on study Patients received cyclophosphamide 50 mg/kg on days -5 and -4, and fludarabine 25 mg/m2 on days -5, -4, -3, -2, -1. Hematopoietic cells from peripheral blood or marrow were infused on day 0. Patients who received hematopoietic cells from cord blood additionally received ATG 30 mg/kg on days -3, -2, -1. Fanconi anemia patients received cyclophosphamide 7.5 mg/kg on days -6, -5, -4, -3, fludarabine 25 mg/m2 on days -6, -5, -4, -3, -2 and ATG 30 mg/kg on days -3, -2, -1 and hematopoietic cells infused on day 0. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
| ||||||||||||||||||||
| Age, Continuous | Median | Full Range | years |
| |||||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||||||
| Region of Enrollment | Number | participants |
| ||||||||||||||||||||
| Diagnosis | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Day 100 TRM | treatment related mortality within 100 days from hematopoietic stem cell (HSC) infusion on day 0 | Posted | Count of Participants | Participants | from start or conditioning (day -6 or -5) through day +100 after HSC infusion |
|
|
| |||||||||||||||||||||||||||
| Primary | Day 100 Best Response | Best disease response measured within 100 days from hematopoietic stem cell (HSC) infusion on day 0 using disease specific response criteria defined in the protocol | Posted | Count of Participants | Participants | from start of conditioning on day -6 or -5 through day +100 after HSC infusion |
|
| ||||||||||||||||||||||||||||
| Secondary | PFS | Progression free survival defined as time from HSC infusion (day 0) until progression of disease or death due to any cause. Patients are censored if alive without disease progression through 1 year after HSC infusion | Posted | Number | 95% Confidence Interval | percentage of participants | 1 year |
|
| |||||||||||||||||||||||||||
| Secondary | OS | Overall survival with events defined as death due to any cause and censored patients are alive as of 1 year post HSC infusion | Posted | Number | 95% Confidence Interval | percentage of participants | 1 year |
|
|
| ||||||||||||||||||||||||||
| Secondary | Acute GvHD | overall grade II-IV acute GvHD | 2 participants died before they were eligible for this outcome | Posted | Count of Participants | Participants | Day +100 |
|
|
|
100 days
SAE=died before absolute neutrophil count recovery (DBE) or survived to day +28 without absolute neutrophil count recovery (FTE) AE=overall grade III-IV acute GVHD
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | All Patients | All patients enrolled on study | 8 | 41 | 3 | 41 | 6 | 41 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| DBE/FTE | Blood and lymphatic system disorders | Serious | Systematic Assessment | died before absolute neutrophil count recovery (DBE) or survived to day +28 without absolute neutrophil count recovery (FTE) |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| acute GVHD grade III-IV | Immune system disorders | Other | Systematic Assessment |
|
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Theresa Hahn, PhD | Roswell Park Comprehensive Cancer Center | 716084505819 | theresa.hahn@roswellpark.org |
| Dec 3, 2019 |
| Prot_SAP_000.pdf |
| ID | Term |
|---|---|
| D009196 | Myeloproliferative Disorders |
| D007938 | Leukemia |
| D008223 | Lymphoma |
| D009101 | Multiple Myeloma |
| D054219 | Neoplasms, Plasma Cell |
| D009190 | Myelodysplastic Syndromes |
| D054437 | Myelodysplastic-Myeloproliferative Diseases |
| D005199 | Fanconi Anemia |
| D000741 | Anemia, Aplastic |
| D015465 | Leukemia, Myeloid, Accelerated Phase |
| D015477 | Leukemia, Myelomonocytic, Chronic |
| D055728 | Primary Myelofibrosis |
| D015466 | Leukemia, Myeloid, Chronic-Phase |
| D000754 | Anemia, Refractory, with Excess of Blasts |
| D008258 | Waldenstrom Macroglobulinemia |
| D054198 | Precursor Cell Lymphoblastic Leukemia-Lymphoma |
| D002051 | Burkitt Lymphoma |
| D006689 | Hodgkin Disease |
| D015470 | Leukemia, Myeloid, Acute |
| D000753 | Anemia, Refractory |
| D015451 | Leukemia, Lymphocytic, Chronic, B-Cell |
| D008224 | Lymphoma, Follicular |
| D012008 | Recurrence |
| D054438 | Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative |
| D018442 | Lymphoma, B-Cell, Marginal Zone |
| D000013 | Congenital Abnormalities |
| ID | Term |
|---|---|
| D001855 | Bone Marrow Diseases |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| D020141 | Hemostatic Disorders |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D010265 | Paraproteinemias |
| D001796 | Blood Protein Disorders |
| D006474 | Hemorrhagic Disorders |
| D029502 | Anemia, Hypoplastic, Congenital |
| D000740 | Anemia |
| D000080984 | Congenital Bone Marrow Failure Syndromes |
| D000080983 | Bone Marrow Failure Disorders |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D049914 | DNA Repair-Deficiency Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D015464 | Leukemia, Myelogenous, Chronic, BCR-ABL Positive |
| D007951 | Leukemia, Myeloid |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D007945 | Leukemia, Lymphoid |
| D020031 | Epstein-Barr Virus Infections |
| D006566 | Herpesviridae Infections |
| D004266 | DNA Virus Infections |
| D014777 | Virus Diseases |
| D007239 | Infections |
| D014412 | Tumor Virus Infections |
| D016393 | Lymphoma, B-Cell |
| D008228 | Lymphoma, Non-Hodgkin |
| D015448 | Leukemia, B-Cell |
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| ID | Term |
|---|---|
| D000961 | Antilymphocyte Serum |
| C081222 | sargramostim |
| D003520 | Cyclophosphamide |
| C042382 | fludarabine phosphate |
| D008775 | Methylprednisolone |
| D009173 | Mycophenolic Acid |
| D016559 | Tacrolimus |
| D036102 | Peripheral Blood Stem Cell Transplantation |
| D036101 | Cord Blood Stem Cell Transplantation |
| ID | Term |
|---|---|
| D007106 | Immune Sera |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| D001688 | Biological Products |
| D045424 | Complex Mixtures |
| D010752 | Phosphoramide Mustards |
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D063088 | Phosphoramides |
| D009943 | Organophosphorus Compounds |
| D011239 | Prednisolone |
| D011246 | Pregnadienetriols |
| D011245 | Pregnadienes |
| D011278 | Pregnanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D002208 | Caproates |
| D000144 | Acids, Acyclic |
| D002264 | Carboxylic Acids |
| D005227 | Fatty Acids |
| D008055 | Lipids |
| D018942 | Macrolides |
| D007783 | Lactones |
| D018380 | Hematopoietic Stem Cell Transplantation |
| D033581 | Stem Cell Transplantation |
| D017690 | Cell Transplantation |
| D064987 | Cell- and Tissue-Based Therapy |
| D001691 | Biological Therapy |
| D013812 | Therapeutics |
| D014180 | Transplantation |
| D013514 | Surgical Procedures, Operative |
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| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| Multiple Myeloma |
|
| Myelodysplastic syndrome |
|
| Fanconi anemia |
|
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|---|
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|---|
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|---|
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| Title |
|---|
| Denominators |
|---|
| Categories |
|---|
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