Neoplasms

Blood and Lymph Conditions

All Conditions

Immune System Diseases

Heart and Blood Diseases

Rare Diseases

Leukemia

Lymphoma

Multiple Myeloma

Neoplasms, Plasma Cell

Hematologic Neoplasms

Hematologic Diseases

Lymphosarcoma

Antineoplastic Agents

All Drugs and Chemicals

Fludarabine

Fludarabine phosphate

Lenograstim

Busulfan

Antimetabolites

Immunosuppressive Agents

Immunologic Factors

Alkylating Agents

Antineoplastic Agents, Alkylating

Busulfan starting 0.8 mg/kg by vein (IV) every 6 hours for 12 doses; Fludarabine 30 mg/m\^2 IV daily for 4 days.

Starting Dose 0.8 mg/kg by vein every 6 hours x 12 doses.

Richard E. Champlin, MD, BS

Objectives:

1. To determine the relative toxicities, engraftment potential, kinetics of engraftment, degree of chimerism and disease control achieved with the combination of fludarabine and busulfan at different dose levels and different dose schedules in patients undergoing allogeneic stem cell transplant (SCT).
2. Determine pharmacokinetics, and toxicity of intravenous busulfan given at equal total dose levels given four times daily, or once daily.
3. In vivo determination of fludarabine inhibitory effects on DNA repair.

Treatment: Participants will have blood tests and bone marrow tests as well as tests to check lung, heart, kidney, and liver functions. Participants will receive busulfan by vein for 2 to 4 days depending on their age and medical condition. All participants will receive fludarabine which will be given over 4 days. Participants undergoing unmatched or matched unrelated donors will receive ATG over 4 days to help with the engraftment of the donor progenitor cells. All drugs are given through the vein daily.

The donor blood cells will be taken from the donor through a process known as apheresis. This will occur after the donor has received 2 days of granulocyte colony stimulating factor (G-CSF) to increase her/his white cell count. The G-CSF will also increase the number of very immature (stem cells) that are to be collected. Apheresis is similar to a platelet donation, but white cells and stem cells are collected instead. About 3 to 5 apheresis procedures will be needed to get enough cells for infusion. If apheresis is not used, donor bone marrow will be taken under general anesthesia.

After the participants receives the donor stem cells, the stem cells divide and reconstitute bone marrow function, blood function, and immunity. The donor stem cells are given after the chemotherapy to shorten the period of low blood counts. They are also given at this time to achieve an antileukemic effect whereby the donor immune cells will recognize the participant's leukemia as "foreign" and prevent its recurrence. A small amount of donor cells will be kept for infusion on a future date (usually 3 and 6 months post transplant) to try to prevent the disease from coming back.

During the 4 to 8 weeks following blood cell infusion, participants will need frequent blood tests to monitor their counts and blood chemistries. Participants will need frequent blood transfusion and may have to be admitted to the hospital to receive antibiotics if they develop fever. Bone marrow will be examined frequently beginning four weeks after treatment to check response. Participants that achieve normal bone marrow and blood counts will be evaluated to determine the most appropriate form of future therapy. Participants who fail to respond to treatment will be offered other therapies.

This is an investigational study. All through all drugs are commercially available. Up to 140 participants will take part in this study. All will be enrolled at UT MD Anderson Cancer Center.

Phase I/II Trial of Fludarabine Plus Busulfan and Allogeneic Progenitor Cell Support

Phase I/II Trial of Fludarabine in Combination With Intravenous Busulfan and Allogeneic Progenitor Cell Support for Patients With Hematologic Malignancies

Continual reassessment method (four times a day) used to determine an MTD, with a target toxicity probability of 20%, where "toxicity" is defined as grade 3 or 4 conventional toxicity \[National Cancer Institute Common Toxicity Criteria (NCI-CTC)\]. Participant evaluation in a cohort with each modality is 30 days.

Tacrolimus and Methotrexate used for acute graft versus host disease (aGVHD) prophylaxis, clinical grading AGVHD criteria (Days 1-100): Grade 1: + to ++ skin rash; no gut involvement; no decrease in clinical performance status; Grade 2: + to +++ skin rash; + gut involvement and/or + liver involvement; mild decrease in performance status; Grade 3: ++ to +++ skin rash; ++ to +++ gut involvement and/or ++ to ++++ liver involvement; marked decrease in performance status; Grade 4: Similar to Grade 3 with ++ to ++++ organ involvement and extreme decrease in performance status.

M.D. Anderson Cancer Center

Busulfan + Fludarabine

Age Continuous

Sex: Female, Male

United States

Region of Enrollment

Richard E. Champlin/Professor

Maximum Tolerated Dose (MTD)

Grade 2

Grade 3-4

Tacrolimus + Methotrexate

Analysis was per protocol for 73 patients out of 80 patients due to 3 early deaths and 4 non engraftments.

Number of Participants With Graft Versus Host Disease (GVHD)

Overall Study

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Phase I/II Trial of Fludarabine Plus Busulfan and Allogeneic Progenitor Cell Support	NCT00506857	Hematologic Mal...	Busulfan Fludarabine	- 75 Years	M.D. Anderson Cancer Center
Phase I/II Trial of Fludarabine Plus Busulfan and Allogeneic Progenitor Cell Support	NCT00506857	Hematologic Mal...	Busulfan Fludarabine	- 75 Years	M.D. Anderson Cancer Center

Spots Global Cancer Trial Database for blood cell infusion