Neoplasms

Blood and Lymph Conditions

All Conditions

Immune System Diseases

Rare Diseases

Leukemia

Preleukemia

Myelodysplastic Syndromes

Lymphoma

Hematologic Neoplasms

Hematologic Diseases

Chronic Graft Versus Host Disease

Lymphosarcoma

Acute Graft Versus Host Disease

All Drugs and Chemicals

Antineoplastic Agents

Anti-Infective Agents

Central Nervous System Depressants

Antirheumatic Agents

Other Dietary Supplements

Tacrolimus

Fludarabine

Fludarabine phosphate

Mycophenolic Acid

Sirolimus

Benzocaine

Cyclophosphamide

Immunosuppressive Agents

Immunologic Factors

Calcineurin Inhibitors

Enzyme Inhibitors

Antineoplastic Agents, Alkylating

Alkylating Agents

Anti-Bacterial Agents

Antibiotics, Antitubercular

Antitubercular Agents

Clotrimazole

Miconazole

Antifungal Agents

Tannic Acid

Pre-BMT :

* Day -6 through -2: Fludarabine 30 mg/m2/day (adjusted for renal function; maximum cumulative dose, 150 mg/m2) administered IV
* Day -6 and -5: Cytoxan 14.5 mg/kg/day administered IV
* Day -1: 400 cGy total body irradiation (TBI) administered in a single fraction

Day 0: Allogeneic blood or marrow transplantation (BMT)

Post-Transplantation Immunosuppression Consisting of:

* Day 3 and 4: High-dose Cytoxan 50mg/kg/day (adjusted according to IBW) administered IV
* Day 5: Sirolimus loading dose 6 mg PO once
* Day 5 thru Day 35: Mycophenolate Mofetil (MMF) 15 mg/kg PO TID (maximum daily dose 3 g/day)
* Day 6 thru Day 180: Sirolimus maintenance dose 2 mg PO QD with dose adjustments to maintain trough of 3 - 12 ng/mL

Pre-BMT:

* Day -6 through -2: Fludarabine 30 mg/m2/day (adjusted for renal function; maximum cumulative dose, 150 mg/m2) administered IV
* Day -6 and -5: Cytoxan 14.5 mg/kg/day administered IV
* Day -1: 400 cGy TBI administered in a single fraction

Day 0: BMT

Post-Transplantation Immunosuppression Consisting of:

* Day 3 and 4: High-dose Cytoxan 50mg/kg/day (adjusted according to IBW) administered IV
* Day 5 thru Day 35: MMF 15 mg/kg PO TID (maximum daily dose 3 g/day)
* Day 5 thru Day 180: Tacrolimus 1 mg administered IV QD

Pre-PBSCT:

* Day -6 through -2: Fludarabine 30 mg/m2/day (adjusted for renal function; maximum cumulative dose, 150 mg/m2) administered IV
* Day -6 and -5: Cytoxan 14.5 mg/kg/day administered IV
* Day -1: 400 cGy TBI administered in a single fraction

Day 0: Peripheral Blood Stem Cell Transplant (PBSCT)

Post-Transplantation Immunosuppression Consisting of:

* Day 3 and 4: High-dose Cytoxan 50mg/kg/day (adjusted according to IBW) administered IV
* Day 5: Sirolimus loading dose 6 mg PO once
* Day 5 thru Day 35: MMF 15 mg/kg PO TID (maximum daily dose 3 g/day)
* Day 6 thru Day 180: Sirolimus maintenance dose 2 mg PO QD with dose adjustments to maintain trough of 3 - 12 ng/mL

Pre-BMT: Cytoxan 14.5 mg/kg/day administered IV; Post-Transplantation: High-dose Cytoxan 50mg/kg/day

Cytoxan

400 cGy TBI administered in a single fraction

Total Body Irradiation

Allogeneic Blood or Marrow Transplant

Peripheral Blood Stem Cell Transplant

Mycophenolate Mofetil

Loading Dose: Sirolimus 6mg by mouth once; Maintenance dose: Sirolimus 2mg by mouth daily

Richard Ambinder, MD

Clinical Trials Office - Sidney Kimmel Comprehensive Cancer Ce

If transplantation using mismatched unrelated donors or non-first-degree relatives could be performed with an acceptable toxicity profile, an important unmet need would be served. Towards this goal, the current study extends our platform of nonmyeloablative, partially HLA-mismatched bone marrow transplant (BMT) and Peripheral Blood Stem Cell Transplant (PBSCT) to the use of such donors, investigating up to several postgrafting immunosuppression regimens that incorporate high-dose Cy. Of central interest is the incorporation of sirolimus into this postgrafting immunosuppression regimen.

The primary goal for phase 1 is to identify a transplant regimen associated with acceptable rates of severe acute GVHD and NRM by Day 100 and for phase 2 estimate the 6-month probability of survival without having had acute grade III- IV GVHD or graft failure.

Reduced Intensity, Partially HLA Mismatched BMT to Treat Hematologic Malignancies

Reduced Intensity, Partially HLA Mismatched Allogeneic BMT for Hematologic Malignancies Using Donors Other Than First-degree Relatives

Two immunosuppressive regimens with Fludarabine-Cytoxan-TBI conditioning will be studied in reduced-intensity, partially HLA mismatched allogeneic BMT from unrelated or non-first-degree related donors. Transplant regimen will be determined by acceptable rates of severe acute GVHD (\< 25%).

Two immunosuppressive regimens with Fludarabine-Cytoxan-TBI conditioning will be studied in reduced-intensity, partially HLA mismatched allogeneic BMT from unrelated or non-first-degree related donors. Transplant regimen will be determined by acceptable rates transplant-related NRM (\< 20%).

Two immunosuppressive regimens with Fludarabine-Cytoxan-TBI conditioning will be studied in reduced-intensity, partially HLA mismatched allogeneic BMT from unrelated or non-first-degree related donors.

All patients will be tracked from Day 0 to date of first objective disease progression, death from any cause, or last patient evaluation. Patients who have not progressed or died will be censored at the last date they were assessed and deemed free of relapse or progression.

All suspected cases of acute GVHD must be confirmed histologically by biopsy of an affected organ (skin, liver, or gastrointestinal tract). Date of symptom onset, date of biopsy confirmation of GVHD, maximum clinical grade, and dates and types of treatment will be recorded. Dates of symptom onset of grade II or higher GVHD and grade III-IV GVHD will be recorded.

National Cancer Institute (NCI)

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Symptoms and General Pathology

Syndrome

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Hodgkin Disease

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Bone Marrow Diseases

Precancerous Conditions

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Acute Non Lymphoblastic Leukemia

Chronic Myeloid Leukemia

Hodgkin Lymphoma

Busulfan

Reduced-intensity transplant with a fludarabine- and busulfan-based preparative regimen. GVHD prophylaxis with cyclophosphamide, tacrolimus, and mycophenolate mofetil.

30 mg/m\^2 IV daily on Day -6 through Day -2.

1 mg/kg PO OR 0.8 mg/kg IV four times daily on Day -6 through Day -3.

15 mg/kg PO three times daily (max daily dose of 3g) starting on Day +5.

Dosed based on drug levels; begin on Day +5 at 1 mg IV daily.

Yvette Kasamon, M.D.

This research is being done to learn more about reduced-intensity bone marrow transplantation (BMT), also known as a "mini" transplant for patients with blood cancers, using bone marrow from a relative.

The main goal of the study is to determine how quickly the donor's bone marrow "takes" in your body. Other goals include describing how many people accept the bone marrow and how quickly the blood counts come up; describing Graft-versus-host disease (GVHD) and other complications; and describing how many people survive without progressive cancer and survive overall

At the present time there are few or no cures for people with cancer of the blood or lymph glands outside of a bone marrow transplant (BMT). BMT has developed over several decades of research as an effective treatment of various malignant and nonmalignant hematologic diseases.

This research is being done to learn more about reduced-intensity bone marrow transplantation (BMT), also known as a "mini" transplant for patients with blood cancers, using bone marrow from a relative. The bone marrow for this transplant comes from a relative who is a half-match or "haplo" match to you. Possible donors include parents, siblings, and children.

"Mini" transplants have been given to many people with various cancers but are considered experimental. Over 200 people at Johns Hopkins have received mini transplants with high doses of cyclophosphamide after the transplant. However, the chemotherapy combination and other treatment given before those transplants were different from what is in this study. Although all of the chemotherapy and immune-lowering drugs used in this study are approved by the Food and Drug Administration (FDA), the combination of medications used in this study are not FDA approved and are experimental.

Reduced-intensity, Related-donor Bone Marrow Transplantation Followed by High-dose Cyclophosphamide for Hematologic Cancers

Reduced-intensity, Related-donor Allogeneic BMT With Fludarabine, Busulfan, and High-dose Posttransplantation Cyclophosphamide for Hematologic Malignancies

Percentage of participants achieving full-donor chimerism in unsorted peripheral blood.

Percentage of participants achieving full-donor chimerism in CD3+ sorted peripheral blood

Percentage of participants alive without disease relapse or progression.

Percentage of participants experiencing disease relapse or progression

Percentage of participants who died due to BMT-related reasons

Percentage of participants experiencing acute and chronic GVHD. Acute GVHD is graded by Przepiorka criteria. Chronic GVHD is graded by NIH consensus criteria and Seattle criteria.

Percentage of participants who failed to engraft.

Data was collected systematically through at least Day 60 by investigator assessment at protocol-specified visits.

Transplant

Fludarabine, Busulfan, Cyclophosphamide, Tacrolimus,: Fludarabine 30 mg/m2 IV once a day for 4 days Busulfan 0.8 mg/kg IV every 12 hours for 4 days Cyclophosphamide 50 mg/kg IV daily for 2 days

BMT Allogenic Transplantation

Age, Continuous

Age, Categorical

Female

Male

Sex/Gender, Customized

United States

Region of Enrollment

Yvette Kasamon

The trial has been terminated early since stopping rule criteria were met (high graft failure rate). Data were not analyzed.

Chimerism in Unsorted Peripheral Blood

Chimerism in CD3+ Sorted Peripheral Blood

Overall Survival

Progression-free Survival

Incidence of Relapse

Non-relapse Mortality

Incidence of Graft-versus-host-disease (GVHD)

Graft Failure

Overall Study

Leukemia, Lymphocytic, Chronic, B-Cell

Bone Marrow Failure Disorders

Pancytopenia

Leukemia, B-Cell

Chronic Disease

Disease Attributes

Myeloproliferative Disorders

Cytopenia

Chronic Lymphocytic Leukemia

Chronic Myeloproliferative Disorders

Fludarabine 30mg/m2 IV days -6 to -2 Cyclophosphamide 14.5 mg/kg IV days -6 and -5 Total body irradiation 2Gy day -1 Stem cell transplant: day 0 Cyclophosphamide 50mg/kg days +3 \& +4

Total body irradiation 12Gy in 8 fractions days -9 to -6 Donor lymphocyte infusion day -6 Cyclophosphamide 60mg/kg IV days -3 \& -2 Stem cell transplant day 0

Reduced intensity haplodentical stem cell transplant

Myeloablative haploidentical stem cell transplant

Dr Kavita Raj

This trial investigates stem cell transplants from partially mismatched donors in patients with blood and bone marrow cancers. The trial will test two kinds of transplants - a full intensity transplant using a high dose of radiotherapy and chemotherapy, and a reduced intensity transplant with lower doses of chemotherapy and radiotherapy. Patients will be entered for the treatment pathway that is most appropriate for their level of health and fitness

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Reduced Intensity, Partially HLA Mismatched BMT to Treat Hematologic Malignancies	NCT01203722	Hematologic Mal...	Fludarabine Cytoxan Total Body Irra... Allogeneic Bloo... Peripheral Bloo... Mycophenolate M... Sirolimus Tacrolimus	6 Months - 75 Years	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Reduced-intensity, Related-donor Bone Marrow Transplantation Followed by High-dose Cyclophosphamide for Hematologic Cancers	NCT01135329	Lymphoma Leukemia Myelodysplastic...	Fludarabine Busulfan Cyclophosphamid... Mycophenolate M... Tacrolimus	6 Months - 75 Years	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Reduced Intensity, Partially HLA Mismatched BMT to Treat Hematologic Malignancies	NCT01203722	Hematologic Mal...	Fludarabine Cytoxan Total Body Irra... Allogeneic Bloo... Peripheral Bloo... Mycophenolate M... Sirolimus Tacrolimus	6 Months - 75 Years	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Trial of Haploidentical Stem Cell Transplantation for Haematological Cancers	NCT01597219	Hodgkin's Lymph... Non-Hodgkin's L... Acute Myeloid L... Acute Lymphobla... Myelodysplastic... Chronic Myeloid... Chronic Lymphoc... Acquired Bone M... Other Haematolo...	Reduced intensi... Myeloablative h...	16 Years - 70 Years	University College, London
Reduced Intensity, Partially HLA Mismatched BMT to Treat Hematologic Malignancies	NCT01203722	Hematologic Mal...	Fludarabine Cytoxan Total Body Irra... Allogeneic Bloo... Peripheral Bloo... Mycophenolate M... Sirolimus Tacrolimus	6 Months - 75 Years	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Reduced-intensity, Related-donor Bone Marrow Transplantation Followed by High-dose Cyclophosphamide for Hematologic Cancers	NCT01135329	Lymphoma Leukemia Myelodysplastic...	Fludarabine Busulfan Cyclophosphamid... Mycophenolate M... Tacrolimus	6 Months - 75 Years	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Spots Global Cancer Trial Database for reduced intensity